Sarcopenic Obesity in Older Adults

REVIEWS
Sarcopenic obesity in older adults:

aetiology, epidemiology and treatment
strategies
John A. Batsis1,2* and Dennis T. Villareal3,4
Abstract | The prevalence of obesity in combination with sarcopenia (the age-related loss of
muscle mass and strength or physical function) is increasing in adults aged 65 years and older.
A major subset of adults over the age of 65 is now classified as having sarcopenic obesity , a
high-risk geriatric syndrome predominantly observed in an ageing population that is at risk of
synergistic complications from both sarcopenia and obesity. This Review discusses pathways and
mechanisms leading to muscle impairment in older adults with obesity. We explore sex-specific
hormonal changes, inflammatory pathways and myocellular mechanisms leading to the
development of sarcopenic obesity. We discuss the evolution, controversies and challenges in
defining sarcopenic obesity and present current body composition modalities used to assess this
condition. Epidemiological surveys form the basis of defining its prevalence and consequences
beyond comorbidity and mortality. Current treatment strategies, and the evidence supporting
them, are outlined, with a focus on calorie restriction, protein supplementation and aerobic and
resistance exercises. We also describe weight loss-induced complications in patients with
sarcopenic obesity that are relevant to clinical management. Finally , we review novel and
potential future therapies including testosterone, selective androgen receptor modulators,
myostatin inhibitors, ghrelin analogues, vitamin K and mesenchymal stem cell therapy.
Adults over the age of 65 constitute 13% of the global and mortality, and highlight evidence-based and novel
1
Sections of General Internal
Medicine and Weight and
population and are the fastest growing demographic therapies targeting this high-risk population.
Wellness, and the Dartmouth subgroup; this group is expected to reach 2.1 billion
Centers for Health and Aging, people in 2050 (ref.1). Within this population, obesity Biological pathways to sarcopenic obesity
Dartmouth-Hitchcock Medical has steadily increased2,3, and in the United States, 38.5% Age-related changes in body composition. Multiple
Center, Lebanon, NH, USA.
of men and 43.1% of women are currently classified as factors are responsible for changes to body composi-
2
Geisel School of Medicine at having obesity4. Worldwide, these rising rates presuma- tion with ageing. Body fat increases until the seventh
Dartmouth, The Dartmouth
Institute for Health Policy and
bly offset gains in life expectancy5, with age-adjusted life decade of life and thereafter decreases13,14. Vertebral
Clinical Practice, The Health expectancy dropping by roughly 0.17 years from 2014 to compression results in a reduction in height15, which
Promotion Research Center 2015 (refs6–10). affects anthropometric measures such as BMI. Muscle
and the Norris Cotton Cancer Sarcopenia , which is the loss of muscle mass and mass declines after peaking in the fourth decade16, such
Center, Dartmouth College,
strength or physical function, naturally occurs in ageing. that weight is mostly gained as fat rather than lean mass.
Hanover, NH, USA.
Sarcopenia synergistically worsens the adverse effects of This age-related reduction in lean mass17,18 accounts, in
3
Division of Endocrinology,
Diabetes and Metabolism,
obesity in older adults, resulting in sarcopenic obesity. part, for reduced resting metabolic rates19. Other aetio-
Baylor College of Medicine, Sarcopenic obesity is appropriately characterized as a logical factors that cause a decline in resting metabolic
Houston, TX, USA. confluence of two epidemics — an ageing population rates include reduced physical activity20, reduced mito-
4
Center for Translational and rising obesity rates11. As elevated BMI, functional chondrial volume and reduced oxidative capacity21,22.
Research on Inflammatory impairment, increased mortality and reduction in Age-related decreases in the components of total
Diseases, Michael E DeBakey quality of life10 are observationally associated, addressing energy expenditure (such as, resting metabolic rates,
VA Medical Center, Houston,
TX, USA.
sarcopenic obesity is important for preventing long- thermic effect of food and physical activity) contribute
term disability in the older adults at high risk12. In this largely to the gradual increase in body fat.
*e-mail: john.batsis@
gmail.com Review, we describe the aetiology and pathogenesis of The age-related decline in resting metabolic rates
https://doi.org/10.1038/ sarcopenic obesity, as well as the associated adverse out- can also result from factors independent of changes to
s41574-018-0062-9 comes for aged individuals beyond reduced function body composition, such as adaptive thermogenesis23,24,
Nature Reviews | Endocrinology

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Reviews
Key points physical function in men >65 years of age with age-
reduced levels of testosterone (serum testosterone
• Body composition changes that occur with the ageing process can lead to sarcopenic concentration <275 ng/dl)53. Levels of dehydroepian-
obesity, an increasingly prevalent disorder owing to the increased prevalence of drosterone sulfate, the biological precursor of testoster-
obesity in an ageing population.
one, also decrease with age in both men and women54,55
• Hormonal, inflammatory and myocellular mechanisms impact underlying biological (for a comprehensive review on the effects of testosterone
processes that promote fat deposition and loss of lean mass and strength.
on body composition see ref.56).
• Definitions of sarcopenia and obesity can vary considerably, prompting difficulties in
the diagnosis and epidemiological understanding of sarcopenic obesity as well as the Inflammatory pathways. A number of inflamma-
development of treatment strategies for this disease.
tory pathways are common to muscle and visceral
• Lifestyle interventions including calorie restriction and physical activity consisting of fat. Obesity activates macrophages, mast cells and
aerobic and resistance exercises are the cornerstones of therapy.
T lymphocytes, promoting a low-level inflammation
• Clinicians and researchers need to be aware of weight loss-induced sarcopenia and that results in the secretion of tumour necrosis factor
osteopenia.
(TNF), leptin and growth hormone (GH)57–59. All such
• Novel, promising therapies, including weight loss medications, bariatric surgery, secretory changes lead to insulin resistance, which is
whole-body vibration therapy, periodization (a systematic variation in physical
increased by muscle catabolism60, promoting gain in
training specificity, intensity and volume within periods), testosterone, selective
androgen receptor modulators, anamorelin, myostatin inhibitors, vitamin K and
fat mass and a loss of muscle mass57. Leptin upregulates
mesenchymal stem cells, require further investigation. the pro-inflammatory cytokines IL-6 and TNF, which
results in a reduction in the anabolic actions of insulin-
like growth factor 1 (IGF1)61. This reduction in IGF1,
which is considered a defence mechanism against weight along with the age-related reductions in testosterone,
loss25. The reduction in energy expenditure as we age is increases the likelihood of incident frailty62. Elevated
not proportionally associated with a reduced drive to cytokine levels observed in hypogonadal states are
eat, which furthers fat build-up and leads to small yearly associated with truncal obesity, which exacerbates the
positive changes in energy balance that might lead to development of sarcopenia44,45. Adiponectin is negatively
weight gain25–27. Considerable inter-individual variabil- correlated with age and obesity and counters the effects
ity to weight loss suggests that adaptive thermogenesis of leptin. Elevated TNF directly inhibits adiponectin63,
Sarcopenia
plays a part in energy balance28 in sarcopenic obesity. arresting muscle protein synthesis and mitochondrial
The loss of muscle mass,
strength or physical function Muscle mass loss with ageing29 correlates with decreased processes64. Obesity also induces leptin resistance,
with age. resting metabolic rates and metabolic adaptation, which promoting reduced muscle fatty oxidation and ectopic
perpetuates the development of obesity30–32. As most fat deposition65,66.
Oxidative capacity individuals with sarcopenic obesity are sedentary, small
The maximal ability of muscle
to utilize oxygen per g of
changes in their muscle mass can markedly alter daily Myocellular mechanisms. A number of mechanisms
muscle per hour. energy expenditure, which in turn affects adaptive might explain the reduction of muscle mass and strength
thermogenesis and exacerbates a vicious cycle in their in sarcopenic obesity, including type II muscle fibre atro-
Thermic effect of food metabolic development33–36. phy, reduction in motor neurons, collagen deposition
The amount of energy
and fibre necrosis67–70. Older adults (those ≥65 years)
expended owing to the body’s
processing and storage of food. Sex-specific hormonal changes: oestrogen and testos- are at risk of developing anabolic resistance owing to
terone. Sex-specific changes in muscle and fat compo- reduced post-prandial amino acid availability, reduced
Fat-free mass sition are partly due to age-related changes in oestrogen muscle perfusion and a reduced digestive capacity
A term interchangeably used and testosterone. In women, menopause increases body resulting from splanchnic sequestration of amino acids71.
with muscle mass and lean
mass; it refers to the mass of all
weight and fat mass, specifically in visceral areas37, but Ageing stimulates the infiltration of fat into mus-
visceral organs, muscles decreases fat-free mass38. This shift in fat deposition to the cle72,73, which might negatively affect sarcopenia74, as
(smooth and skeletal), bones, centre of the body (which accounts for 15–20% of total described below, and obesity promotes the deposition
ligaments and tendons but fat stores) expands waist circumference and reduces mus- of fat in the liver, heart, pancreas and skeletal muscle
does not include fat that is
cle mass38–40. Oestrogen can attenuate these changes41 by (Fig. 1). The deposition of intramyocellular lipids promotes
present in the marrow of bones
or internal organs. modulating inflammation in skeletal muscle through lipotoxicity and inflammation and induces dediffer-
satellite cell activation42,43. entiation of mesenchymal adipocyte-like progenitor
Waist circumference In males, testosterone promotes muscle regenera- cells that express fatty tissue genes75. The regeneration
An anthropometric measure of tion through satellite cell activation44,45. Testosterone potential of muscle is impaired, which might promote
central obesity (subcutaneous
and visceral) measured at the
levels decline by approximately 1% per year, which fibrosis, thereby promoting insulin resistance76–79, par-
level of the iliac crest. can negatively affect muscle mass and fat distribution tially owing to impaired mitochondrial fatty acid oxi-
in ageing46. Testosterone levels in the highest quartile dation and increased lipolysis76,80. A reduction in the
Visceral fat (496–1,340 nmol/l) are associated with reduced lean number of mitochondria and elevated production of
A measurement of the
muscle loss47 and reduced visceral fat redistribution48 reactive oxygen species occur in muscle following the
adiposity located among
organs within the abdominal in older men aged ≥65 years and in individuals with deposition of intramyocellular lipids. This process can
cavity; it is associated with obesity49. Testosterone increases muscle protein syn- impair muscle function and might reduce the oxidative
inflammation and increased thesis by increasing amino acids utilization in skeletal capacity of muscle81. Potential mechanisms explaining
cardiometabolic risk. muscle and increases androgen receptor expression44,45,50. these changes include age-related reductions in protea-
Intramyocellular lipids
Current data on supplementation for muscle strength- some activity, deficiencies in ubiquitylation and auto-
Fat depositions within the ening are conflicting51,52. A 2016 study reported that phagy and impairments in removing degraded proteins
muscle structure. treatment with testosterone for 1 year did not improve and end products82–84.
www.nature.com/nrendo
Reviews
Overeating Lack of exercise

Ageing Protein intake Promotes sarcopenia:
↓ Muscle mass
Protein needs ↓ Strength
Obesity Insulin resistance owing to ↓ Physical function
physical illness
• Testosterone
• Oestrogen
Adipocyte
Muscle
Mesenchymal regeneration
Myostatin progenitor cell
Mast • TNF
cell • IL-6 IGF1
• Leptin
Inflammation
Ectopic T cell
deposition of Intramyocellular • Muscle contractility
fat: lipid deposition Lipotoxicity • Muscle protein
• Liver synthesis
• Pancreas
• Heart
• Other organs
Macrophage Adiponectin Mitochondria
activation function
Fat oxidation Lipolysis
Muscle
Fig. 1 | A proposed model of mechanisms leading to sarcopenic obesity. The proposed interplay between adipose and
muscle tissue, which is believed to contribute to the development of sarcopenic obesity , is shown. The black lines are
stimulatory , while red lines with flat ends indicate inhibition. IGF1, insulin-like growth factor 1; TNF, tumour necrosis factor.
Pro-inflammatory lipids also secrete paracrine hor- increase muscle protein synthesis in older adults despite
mones and cytokines that promote a feedforward cycle age-related decreases in anabolic signalling106–109. Muscle
by producing intramyocellular lipids. This lipotoxicity satellite cells located between myofibres and their sur-
impairs muscle fibre contractility and interferes with rounding basal lamina are recruited into existing muscle
muscle protein synthesis, exacerbating sarcopenia82–84. fibres by physical activity110,111. Muscle injury activates
Lipid deposition can also occur in spaces previously satellite cells to regenerate muscle by releasing IGF1,
occupied by muscle, impairing new muscle tissue fibroblast growth factor and mechano growth factor, all
growth. One study reported an increase in intramyo- of which stimulate the differentiation and proliferation of
cellular lipid deposition after young, healthy men and muscle satellite cells112,113. Circulating inflammatory bio-
women aged 19–28 years were exposed to 30 days of leg markers, including IL-6, C-reactive protein and TNF, are
disuse, which resulted in lower extremity muscle mass downregulated by aerobic exercise and strength train-
loss85. This finding could be due to skeletal muscle pref- ing, although the relationship is less clear with combined
erentially depositing fat for a source of energy as opposed aerobic and resistance activities114–118. Elevated levels of
to glucose86,87. While muscle cells can regenerate through IL-6 and TNF and low levels of IGF1 are associated
satellite mesenchymal progenitor cells, their numbers with reduced muscle mass, reduced muscle strength,
decline with age, which contributes to reduced muscle reduced muscle mobility and reduced muscle function,
function88,89. Myostatin can be upregulated in skeletal suggesting a marked role of exercise in attenuating these
muscle, inhibiting muscle genesis90. In sum, individuals muscular changes with ageing117,119,120.
with obesity are at risk of inflammation, which can lead Aerobic activity can improve the oxidative capacity
to the preferential mobilization of muscle instead of fat91. of muscle by counteracting the negative effect of intra
myocellular lipids and accelerating lipolysis, which results
The role of exercise. Exercise can affect hormonal bal- in an increase in capillary density121. The synthesis of
ance, reduce oxidative stress, induce mitochondrial mitochondria in myocytes is upregulated to meet the
synthesis, alter immunological and motor function and demands associated with an increase in capillary density,
improve muscle oxidative capacity92–95. Increased muscle which in turn leads to increased oxygen extraction
Myostatin protein synthesis with exercise sensitizes muscle insu- and metabolism122 through the induction of calcium and
A transforming growth factor- lin action and promotes anabolism96–100. Sarcopenia is metabolic signalling pathways such as those involv-
related protein that is associated with reduced muscle protein synthesis, partly ing 5′-AMP-activated serine/threonine-protein kinase
synthesized and secreted in
skeletal muscle and negatively
owing to decreased anabolic stimulation (which can (AMPK) and sirtuins123. These mediators stimulate
regulates muscle mass and result from a lack of regular exercise). Aerobic exercise101, mitochondrial production, which promotes improved
function. resistance training 102–104 and their combination 105 fatty acid metabolism124.

Reviews
Myocyte apoptosis can be abrogated by physical the effects of aerobic activity in patients who had recov-
activity125,126, while mechanisms of cellular quality con- ered from breast cancer reported that individuals who
trol, including autophagy, mitophagy and mitochondri- were randomized to the aerobic exercise group demon-
ogenesis127, contribute to the development of sarcopenic strated reductions in insulin and leptin and increases in
obesity and could be potential targets for therapy. the adiponectin:leptin ratio but no significant changes
Reduced cytokine production can lead to improved in adiponectin compared with participants in the usual
glucose metabolism, insulin sensitivity and muscle pro- activity group148. These results parallel those from studies
tein synthesis, which might dampen the progression of in inactive men aged 65–82 years who were overweight.
sarcopenic obesity. Investigators assigned participants to partake in vary-
Ageing leads to reduced cardiopulmonary status ing intensities of resistance exercises. The investigators
owing to inefficient oxygen extraction and a concomi- reported no alterations in concentrations of leptin, but
tant reduction in metabolically active muscle mass128. participants had intensity-dependent changes in adiponec-
Peak oxygen consumption is potentially inversely tin139,145 — high-intensity resistance training led to an
related to frailty129,130, suggesting that improvements increase in the concentrations of adiponectin for 24 hours
in VO2 max following aerobic training counteract after exercise in inactive adults who were overweight139.
frailty131,132. Following a 12-week diet–exercise interven-
tion in male and female frail adults with obesity aged Summary of mechanisms. The core biological factors
69 ± 1 years, investigators reported reduced skeletal that underlie sarcopenic obesity are age-related changes
muscle levels of mRNA for TLR4, IL6 and TNF, increased in metabolism and body composition and the presence
mechano growth factor mRNA and increased fat-free of concurrent environmental obesogenic factors and
mass in the exercise group, and these results were inde- physical illnesses that develop with the ageing process.
pendent of weight loss133. Separately, resistance exercises Incremental metabolic changes over time promote fat
resulted in increased TNF mRNA and protein from skel- deposition with a pro-inflammatory cascade of events.
etal muscle biopsy samples in frail adults134. Expression In tandem, crosstalk with biologically active muscle tis-
of skeletal muscle TNF, IL-1β and nitric oxide synthase, sue leads to a negative feedback cycle that promotes pro-
inducible in patients with heart failure was reduced fol- gressive gain in fat mass and loss of lean mass and muscle
lowing aerobic training, suggesting that aerobic exercise strength. In a pre-frail and frail population, a strategy
has anti-inflammatory effects135. Furthermore, a 12-week combining physical training and nutritional intervention
aerobic and resistance programme increased serum levels was more likely to result in stable or reduced IL-6 lev-
of ghrelin and adiponectin by 47% and 55%, respectively, els in individuals who demonstrated improved physical
and reduced circulating levels of CD14+ and CD16+ performance than in those with lower physical perfor-
inflammatory monocytes, adding additional evidence to mance149. Calorie restriction and physical activity might
the anti-inflammatory effects of exercise136. impede and halt these processes. While we have a better
Resistance exercise increases the number and size of understanding of the role of physical activity in reversing
fast twitching muscle fibres (IIA and IIX), which improve sarcopenic obesity, the effect of a lifetime of inactivity on
glucose metabolism in muscle and muscle protein synthe- the development of sarcopenic obesity is still unclear.
sis102,103,137–139. Muscle protein synthesis is also improved by
nutrient-stimulated vasodilation and nutrient transport Assessing body composition
to local muscle myofibrils112,124. Muscle fascicle length Gold standard methods to assess body composition,
and muscle tendon stiffness reportedly increased after including CT and MRI, allow clinicians to accurately
strength training (leg press and extension) over 14 weeks analyse adipose tissue and muscle mass150 (Fig. 2). Steven
in a cohort of men and women aged over 65 years140. In a Heymsfield and colleagues have argued the impor
study of eight young adults (aged 18–29 years) and seven tance of using measures beyond muscle mass when
older adults (aged 67–81 years), isometric knee extension diagnosing sarcopenic obesity151. The strengths and
at varying degrees of maximal voluntary contraction fol- limitations of each method to assess body composition
lowed by a 6-week resistance programme demonstrated to diagnose sarcopenia and sarcopenic obesity have been
early increases of isometric knee extensor maximal force reviewed elsewhere152–155.
(which is a marker of voluntary muscle contraction) and Dual-energy X-ray absorptiometry (DXA) is recom-
VO2 max increases in motor unit discharge rates (which is a magni- mended for the assessment of appendicular lean mass in
The maximal amount of tude of the speed of neural activation)141. Resistance train- the diagnosis of sarcopenia156 owing to its affordability,
oxygen used per kg of body
weight during maximal
ing has also been shown to reduce levels of cytokines, availability and diagnostic accuracy157. DXA correlates
exercise. such as resistin, leptin and IL-6 (ref.142). well with gold standard measures of body composition,
Leptin and adiponectin stimulate and inhibit, respec- such as MRI, and with bioelectrical impedance, which
Lean mass tively, the deposition of intramuscular lipids (Fig. 1); can also measure fat and segmental muscle mass158–160.
A term that refers to the mass
however, defining their precise roles in physical activity Assessments of lean mass are highly reproducible and
of all visceral organs, muscles
(smooth and skeletal), bones, continues to be challenging. For instance, the concen- can be used for clinical monitoring, while a detailed
ligaments and tendons but tration of leptin in the systemic circulation is suppressed assessment of visceral fat is not as accurate150,161–163.
excludes fat from bone. following resistance exercise143 but also in individuals In a 2013 report by the International Society for Clinical
with overweight or obesity following a physical training Densitometry, the recommendation to perform DXA for
Appendicular lean mass
Muscle mass consisting of the
intervention143–145. Resistance training seems to be more assessing total body composition and for a regional ana
sum of the upper and lower efficient in reducing leptin levels than aerobic training lysis of fat and muscle in patients with muscle weakness
limbs. alone146, though conflicting evidence exists147. A study into or poor physical function was categorized as fair157.
Reviews
part a part b Sarcopenia (IWGS) provided a consensus definition for

sarcopenia180 as the combination of low whole-body or
appendicular lean mass and poor physical functioning
(gait speed ≤1 m/s). The European Working Group for
the Study of Sarcopenia (EWGSOP)156 identified sarco-
penia cut-off points and tools for its measurement. They
recognized the lack of diagnostic criteria for sarcopenia
but integrated low muscle mass and function (strength
or performance) in their terminology, believing that the
relationship between these two measures is not linear nor
Fig. 2 | Mri of individuals with and without obesity. Cross-sectional MRI of the bidirectional73,156,181. This algorithm was meant for clini-
quadriceps area of an individual without obesity with normal muscle characteristics cal application using gait speed (<0.8 m/s) before muscle
(part a) and an individual with obesity with small muscles and infiltration by adipose
mass or strength measurement. EWGSOP recommended
tissue (part b) is shown. More muscle tissue is visible in part a than in part b, and the
higher intensity signals seen in part b indicate fat infiltration of the muscle. Images that muscle mass is assessed by DXA or bioelectrical
courtesy of Edward Weiss, St Louis University School of Medicine, St Louis, MO, USA. impedance, using mathematical thresholds and formulas
presented in their consensus document. Hand grip strength
cut-off points are dependent on an individual’s BMI.
Bioelectrical impedance is a simple, non-invasive, inex- The Foundation for the National Institutes of Health
pensive, rapid and portable diagnostic tool. Reductions in (FNIH) Sarcopenia Project182 suggested a causal, indi-
muscle mass result in an increase in connective tissue164–166 rect relationship between muscle mass and function
that can interfere with the assessment of muscle mass. in their definition of sarcopenia. The FNIH suggested
Variable hydration status also impacts its accuracy167. testing for low lean mass using DXA (defined using
To use bioelectrical impedance, tissue hydration must appendicular lean mass) and reduced muscle function
be constant and the body must be cylindrical168,169; both using handgrip strength. FNIH stated that sex-specific
assumptions are challenged in sarcopenia and obesity. cut-off points could be adjusted for BMI. The separate
Thus, an overestimation of the total volume of water and criteria for muscle mass and strength implied the need
extracellular fluid in the body leads to aberrant values. to target interventions for individuals with low mass or
Further, whether the bioelectrical impedance prediction low strength. FNIH deliberately avoided the term sarco-
equations are valid when applied to different ethnic groups penia to differentiate between qualitative (strength) and
is unclear170, despite specific adaptations and adjust- quantitative (mass) components.
ments171–173. Biological differences between different ethnic These definitions provide excellent negative percent
populations might influence the relationship between agreements on the absence of sarcopenia; however, there
skeletal mass and resistance174. Other notable limitations is poor overlap in identifying individuals with sarcope-
include large standard errors and population specificity175. nia183. Ethnic-specific differences result in inaccurate
Cut-off points might not capture such determinants, par- prevalence estimates184. The Asian Working Group for
ticularly when levels of fat mass are high, which questions Sarcopenia185 provided guidance for individuals of Asian
the utility of bioelectrical impedance for the assessment of descent. They suggested using handgrip strength and
body composition by professional societies169 who recom- gait speed for initial testing and/or screening followed by
mend adjustment to population-specific, age-appropriate the EWGSOP approach for muscle mass measurement,
equations169,176. Further validation of bioelectrical imped- strength and physical performance, with different, lower,
ance results is needed in individuals aged ≥80 years, as cut-off points (Table 1).
they are at increased risk of sarcopenic obesity177,178. Obesity is defined as an unhealthy excess body fat
Of note, current bioelectrical impedance systems permit that increases the risk of medical illness and mortality186.
an improved protocol that involves segmental analyses in As with sarcopenia, no consensus defines obesity cut-
clinical settings, as reviewed elsewhere179. off points. Instead, cut-off points are premised on sex-
specific, whole-body DXA. The American Association
An evolving definition of Clinical Endocrinology187 recommends the use of the
The current definitions of sarcopenic obesity are based WHO body fat thresholds for the diagnosis of obesity —
on the individual definitions of sarcopenia and obesity (men >25% body fat and women >35% body fat). The
(Table 1), but presently there is no consensus that defines WHO thresholds also used BMI for obesity (≥30 kg/m2) or
the cut-off points for either of these diseases, which waist circumference (men ≥102 cm and women ≥88 cm)
makes arriving at an accurate diagnosis of sarcopenic as a visceral fat surrogate. The International Society of
obesity challenging. The term sarcopenia is defined dif- Clinical Densitometry, the American Heart Association
ferently throughout the literature (Table 1), leading to and The Obesity Society all recognize the lack of spe-
confusion in the medical community and preventing any cific thresholds, while the American College of Sports
inter-study comparisons. Without a consistent definition Medicine suggests cut-off points of 28% and 35% for
Grip strength of sarcopenia, investigators are limited in their ability to men and women, respectively188,189. Others applied math-
A measurement used in the identify participants for interventional research. ematical body fat thresholds of reference populations
ascertainment of upper
Current definitions of sarcopenia incorporate var- to provide sufficient power that might not be based on
extremity strength; it is
assessed using the dominant
iations of muscle mass, strength and anthropometric distal outcomes190,191. Body fat has better predictive valid-
hand with a hand-held measures including mid-arm and calf circumference. ity on the development of the metabolic syndrome192 and
dynamometer. The International Working Group for the Study of cardiovascular disease risk193 than BMI.

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Table 1 | Selected definitions of sarcopenia with or without obesity

Author, year Sarcopenia Measurement modality obesity Validated population
and study component (cut-off points) component
name (when (cut-off points)
applicable)
Newman, 2003 ALM divided by DXA (men <7.23 kg/m2; BMI (≥30 kg/m2) New Mexico Elder
(ref.469) height squared women <5.67 kg/m2) Health Survey
ALM divided by DXA (lowest twentieth BMI (≥30 kg/m2) Health ABC study
height and fat mass percentile of residuals
(sex-specific))
Baumgartner, ALM divided by DXA (men <7.26 kg/m2; Body fat (men >27%; New Mexico Aging
2000 (ref.470) height squared women <5.45 kg/m2) women >38%) Process Study
Baumgartner, ALM divided by DXA (men <7.26 kg/m2; Body fat (men ≥28%; New Mexico Elder
2004 (ref.191) height squared women <5.45 kg/m2) women ≥40%) Health Survey
Villareal, 2005, ALM divided by ALM (<5.45 kg/m2, sex is not BMI (≥30 kg/m2) Young healthy
ASN–TOS186 height squared specified) population
Bouchard, 2009 ALM divided by DXA (men <8.51 kg/m2; Body fat (men ≥28%; Nutrition as a
(ref.188) height squared women <6.29 kg/m2) women ≥35%) Determinant of
Successful Aging study
Fielding, 2011, Physical function Gait speed (<1 m/s) NA NA
IWGSP180
Lean mass DXA (less than the twentieth NA Health ABC
percentile healthy adults,
ALM divided by height
squared: men ≤7.23 kg/m2;
women ≤5.67 kg/m2)
Cruz-Jentoft, ALM divided by DXA (men ≤7.26 kg/m2; NA Rosetta study
2010, height squared women ≤5.50 kg/m2)
EWGSOP156
DXA (men ≤7.25 kg/m2; NA Health ABC study
DXA (men ≤7.23 kg/m2; NA Health ABC study
Residuals DXA (ALM (fat mass divided NA Health ABC study
by height), men: −2.29;
women: −1.73)
SMI divided by BIA (men ≤8.87 kg/m2; NA Taiwanese population
height squared women ≤6.42 kg/m2)
ALM divided by (men: severe ≤8.50 kg/m2, NA NHANES III study
height squared moderate 8.51–10.75 kg/m2.
Women: severe ≤5.75 kg/m2;
moderate 5.76–6.75 kg/m2)
Muscle strength Handgrip strength (men NA InCHIANTI study
<30 kg; women <20 kg)
Muscle strength Handgrip strength (males: NA Cardiovascular Health
based on BMI BMI <24 kg/m2: <29.0 kg; Study
category BMI 24.1–26.0 kg/m2: <30.0 kg;
BMI 26.1–28.0 kg/m2: <30.0 kg;
and BMI >28 kg/m2: <32.0 kg;
females: BMI <23 kg/m2:
<17.0 kg; BMI 23.1–26.0 kg/m2:
<17.3 kg; BMI 26.1–29.0 kg/m2:
<18.0 kg; and BMI >29 kg/m2:
<21.0 kg)
Physical SPPB (≤8) NA EPESE study
performance
Gait speed over 6 m (<1 m/s) NA Health ABC study
Gait speed over 6 m NA Health ABC study
(<1.175 m/s)
Gait speed over 15 ft NA Cardiovascular Health
(men ≤1.73 m: <0.65 m/s; and Study
>1.73 m: <0.76 m/s;
women: ≤1.59 m: <0.65 m/s;
and >1.59 m: <0.76 m/s)
Gait speed over 4 m (<0.8 m/s) NA InCHIANTI study
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Table 1 (cont.) | Selected definitions of sarcopenia with or without obesity

Author, year Sarcopenia Measurement modality obesity Validated population
and study component (cut-off points) component
name (when (cut-off points)
applicable)
Studenski, 2014, Weakness Handgrip strength NA Multiple study cohorts
FNIH182 (men <26 kg; women <16 kg)
Handgrip strength:BMI NA Multiple study cohorts
(men <1.0; women <0.56)
ALM Men <19.75 kg; women NA Multiple study cohorts
<15.02 kg
ALM:BMI Men <0.789; women <0.512 NA Multiple study cohorts
Asian Working ALM divided by DXA (men <7.0 kg/m ; 2
NA NA
Group for height squared women <5.4 kg/m2)
Sarcopenia,
2014 (ref.185) BIA (men <7.0 kg/m2; NA NA
women <5.7 kg/m2)
Strength Handgrip strength NA NA
(men <26 kg; women <18 kg)
Performance Gait speed over 6 m (<0.8 m/s) NA NA
ABC, Ageing, Body and Body Composition; ALM, appendicular lean mass; ASN, American Society of Nutrition; BIA , bioelectrical
impedance; DXA , dual-energy X-ray absorptiometry ; EPESE, Established Populations for the Epidemiologic Study of the Elderly ;
EWGSOP, European Working Group on Sarcopenia in Older People; FNIH, Foundation for the National Institutes of Health; IWGSP,
International Working Group on Sarcopenia; NA , not applicable; NHANES, National Health and Nutrition Examination Survey ;
SMI, skeletal muscle index; SPPB, short performance physical battery ; TOS, The Obesity Society.
Body composition modalities have advantages and showed that definitions for sarcopenia were highly
disadvantages in assessing changes in fat or muscle dependent on mathematical thresholds, reference pop-
distribution. We suggest DXA for research purposes, ulations and muscle mass definitions. A comparison
as it is more readily available to provide the necessary of the rates of sarcopenic obesity using bioelectrical
information. If DXA is unavailable, a stand-alone or impedance to define sarcopenia and percentage of body
portable bioelectrical impedance system can be used. fat to define obesity showed increasing rates with age196.
We advocate caution when using bioelectrical imped- In another study, the authors identified individuals
ance equations; they must account for age, sex, levels of with a BMI ≥35 kg/m2 and evaluated the prevalence of
physical activity, body fat and ethnicity. Feasible anthro- sarcopenic obesity using DXA-defined body fat in 120
pometric indices as surrogates for adiposity, including predominantly female adults (46.9 ± 11.0 years). The
BMI and waist circumference, have poor sensitivity. investigators reported rates that ranged from 0–84.5%
In one study, BMI correctly classified 41.0% of men and in women to 0–100% in males depending upon the defi-
45.1% of women as being obese and waist circumference nition applied197. In a population-based cohort using
correctly classified 64.2% of men and 81.0% of women as National Health and Nutrition Examination Survey
being obese194. We believe that anthropometric measures (NHANES) data that applied the aforementioned FNIH
should be used with great caution when assessing body criteria for appendicular lean mass, rates of sarcopenic
composition and only if other imaging is unavailable. obesity were 12.6% in men and 33.5% in women. The
With ageing, fat preferentially accumulates both vis- rates of sarcopenic obesity increased with age, reaching
cerally and ectopically rather than as abdominal subcu- 48.0% and 27.5% in females and males, respectively, in
taneous fat. Rapid accumulation of intra-abdominal fat those aged over 80 years198. In a cohort of individuals
is exacerbated by physical inactivity, hormonal changes, from South Korea’s Korean Sarcopenic Obesity Study, an
reduced responsiveness to thyroid hormone and leptin ongoing epidemiological, prospective cohort of healthy
resistance186. As central fat accumulation predominates, volunteers aged 20–80 years, prevalence of sarcopenic
and loss of muscle occurs peripherally, the prototype obesity ranged from 1.3–15.4% in men to 0.8–22.3%
of sarcopenic obesity is easily recognized (‘fat frail’). in women199.
This prototype is not inconsistent with intramuscular The prevalence of low muscle strength with obesity is
fat accumulation, which contributes to inflammation, less clear. Data from the InCHIANTI study noted rates
Knee extensor strength mitochondrial dysfunction and insulin resistance within of 3.2–8.7% using the low knee extensor strength with
A measure of lower extremity
muscle and reduces muscle protein synthesis74,195. either high BMI or waist circumferrence200. Investigators
strength. The test is performed
using a dynamometer with the from the Cardiovascular Health Study used low grip
participant sitting with hips and Prevalence of sarcopenic obesity strength and high waist circumference to define low
knees flexed at 90°; the A shortcoming in ascertaining accurate prevalence muscle strength and obesity. Rates approached 11.1%201,
participant extends his or her rates for sarcopenic obesity is the lack of a consistent while data from FNIH classified 4.1% of men and 14.0%
knee and pushes against a
resistance pad — the results
definition for either sarcopenia or obesity. A review of of women as having sarcopenic obesity using high BMI
are measured in kilograms eight definitions for sarcopenic obesity noted a 19-fold and low grip strength as measures of obesity and low
or pounds. to 26-fold variation in sex-specific rates178. The analysis muscle strength, respectively202. Overlap using different

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Quadriceps muscle area

diagnostic criteria of sarcopenic obesity is limited183 as defined by BMI and low muscle strength200. An increase
Cross-sectional 2D area at the but ranges from 2.1% to 4.1%. These findings are also in mobility disability and risk of hospitalization (OR 2.10,
level of the quadriceps muscle observed when evaluating the overlap of sarcopenia-only 95% CI 1.14–3.88) was associated with low muscle strength
of the lower limb. definitions, which is less than 50%183. and abdominal obesity in an 11-year follow-up study
(OR 1.36, 95% CI 1.04–1.78). High BMI and low muscle
Consequences of sarcopenic obesity strength were related to limitation in mobility at 2-year
Cross-sectional and longitudinal studies are subject to follow-up (OR 3.88, 95% CI 1.08–13.91)212. In another
the same definitional challenges as prevalence studies. study, abdominal visceral fat and quadriceps muscle area
Despite the crucial need for a consensus definition, here served as markers for central obesity and sarcopenia,
we describe the clinical importance of sarcopenic obesity. respectively, and were associated with postural instability213.
Disability or impairments. Richard Baumgartner and Metabolic impairments. A study from the South Korean
colleagues were the first to characterize the association NHANES conducted an evaluation of sarcopenia
between sarcopenia (as defined by appendicular lean (as defined by muscle mass) with obesity (as defined by
mass) and percent body fat on incident disability191. a BMI ≥25 kg/m2). The authors reported that individu-
In their analysis, when compared with a healthy body als with sarcopenic obesity were at an increased risk of
composition, sarcopenic obesity was associated with a dyslipidaemia (OR 2.82, 95% CI 1.76–4.51)214 and had
relative risk of incident disability over 8 years that was significant positive associations with insulin resistance as
2.63 (95% CI 1.19–5.85). In addition, when compared defined by HOMA scores and triglycerides215. In another
with a healthy body composition, a combination of obe- study, low handgrip strength and high waist circumference
sity, as defined by percentage of body fat, with low mus- and/or BMI were significantly associated with elevated
cle mass represented odds ratios of difficulty ascending levels of IL-6, C-reactive protein and IL-1 (ref.57) but con-
and descending stairs that were 2.60 and 2.35 higher, flicted with results using the FNIH criteria to define low
respectively203. The Concord Health and Aging project204 lean mass216. By contrast, low muscle strength (as defined
used the FNIH criteria for sarcopenia with elevated body by the FNIH criteria) with an elevated BMI was not asso-
fat to evaluate frailty and reported that sarcopenic obe- ciated with differences in metabolic components among
sity resulted in an increased risk of frailty (OR 2.00, 95% groups of postmenopausal women aged 55–75 years217.
CI 1.42–2.82), activity of daily living disability (OR 1.58,
95% CI 1.12–2.24) and instrumental activity of daily liv- Comorbidities. Individuals with sarcopenic obesity
ing disability (OR 1.36, 95% CI 1.05–1.76). The above have a higher risk (OR 3.51, 95% CI 2.15–5.75) of radio
results contrast with an earlier cross-sectional study graphic knee osteoarthritis218 than individuals in the
that defined sarcopenic obesity by low muscle mass non-sarcopenic obesity group. One study reported that
and elevated body fat and did not demonstrate differ- risk of falling was highest in individuals with low muscle
ences in disability compared with controls205. Another mass and/or strength with obesity as defined by percent-
group used DXA to assess body mass and its relation- age of body fat219, but spine and total BMD were lower in
ship with physical capacity and found mixed results188. individuals who were sarcopenic obese and dynapenic
Data from the Quebec Longitudinal Study applied defi- obese than in individuals with obesity alone220. A study
nitions of sarcopenic obesity comprising Baumgarter’s that evaluated participants over 6 years reported that the
definitions of sarcopenia and obesity as defined by body combination of obesity as defined by BMI and low hand-
fat191 and found global physical capacity scores were grip strength suggested an increased risk of type 2 diabe-
no different between obese groups (sarcopenia versus tes mellitus (OR 3.57, 95% CI 2.04–6.24), an association
non- s arcopenia (P = 0.14 in men and P = 0.19 in that was not observed with cardiovascular disease221. The
women)), but lower scores were observed than with the rate of depression has been reported as being highest in
non-sarcopenic non-obese group (P < 0.05)188. Women patients with sarcopenic obesity (defined as low handgrip
with sarcopenia alone had higher scores than people with strength and obesity defined by BMI) (OR 1.79, 95% CI
obesity without sarcopenia and than individuals 1.10–2.89) over 4 years222 compared with non-obese indi-
with obesity and sarcopenia (P < 0.01). viduals in the highest tertile of grip strength. These data
Muscle strength is a stronger predictor of long-term were confirmed in another study that defined sarcopenic
functional decline than muscle mass206. Data from the obesity as low muscle mass or muscle strength, with obe-
Osteoarthritis Initiative showed that a combination of sity defined by percentage of body fat223. Individuals with
low knee extensor strength with high BMI was asso- low muscle mass and high waist circumference had worse
ciated with reduced gait speed and reduced Late-Life psychological health and higher stress than individuals
Function and Disability Index and Short Form-12 with normal muscle mass and normal waist circumfer-
scores207, which indicate a lower degree of physical ence. Finally, an area of interest for researchers now is
function208 and decreased self-reported health status209. the role of sarcopenic obesity in cancer224, which further
Low handgrip strength and elevated BMI were strongly demonstrates its relationship with adverse health events.
associated with an increased risk of functional decline210.
In addition, data from the UK Biobank study found an asso- Mortality. Epidemiological studies investigating the
ciation between high BMI, low grip strength and reduced relationship between sarcopenic obesity and mortality
long-term physical activity211. Data from the InCHIANTI have reported conflicting results198,204,221,225–228. A longi-
study showed that mobility disability trajectories and gait tudinal study from 2017 demonstrated small differences
speed over 6 years were steepest in individuals with obesity in all-cause mortality between obesity as defined by both
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Table 2 | Potential approved therapies in sarcopenic obesity

component goal Suggested approach
Calorie restriction Lose body fat and improve physical 500–1,000 kcal per day
function
~0.5 kg per week aiming for 8–10% weight
loss at 6 months followed by weight loss
maintenance
No specific diets are proven in this
population
Aerobic exercises Improve cardiorespiratory fitness 150 min per week of moderate to vigorous
aerobic exercise
Resistance exercises Improve muscle strength and mass; 60–75 min of resistance training 3 times
attenuate loss of muscle and bone weekly , separated by one day focusing on
during weight loss efforts strength, balance and flexibility
Protein supplementation Mitigate loss of muscle mass and 1.0–1.2 g/kg per day of protein in divided
strength doses (25–30 g daily)
2.5–2.8 g leucine daily
Calcium supplementation Prevent potential disturbances in bone 1,200 mg per day of supplemental
metabolism calcium, preferably through dietary
measures
Vitamin D supplementation Prevent potential disturbances in bone 1,000 IU vitamin D per day , ideally
metabolism maintaining blood levels ≥30 ng/ml
IU, international units.
BMI and low muscle strength and low muscle strength individuals with normal indices236. The EuroQOL score was
alone229. Others showed that mortality was significantly dependent on cardiovascular fitness rather than sarcopenic
elevated in people with sarcopenic obesity, which was obesity237. Future studies need to focus on health-related
defined using mid-arm circumference (HR 1.46, 95% quality of life and patient-reported outcomes in sarcopenic
CI 1.23–1.73) and muscle strength with waist circumfer- obesity before we are able to draw firm conclusions.
ence (HR 1.23, 95% CI 1.09–1.38)230. Sarcopenic obesity
(defined by muscle mass assessed by bioelectrical imped- Institutionalization and health-care utilization. Few
ance and percentage of body fat) was associated with studies, and no known longitudinal studies, have eval-
an increased mortality (HR 1.29, 95% CI 1.03–1.60)230. uated the relationship between sarcopenic obesity and
Muscle strength also affects mortality independent of institutionalization. Peggy Cawthon and colleagues238
muscle mass. Investigators from the Health, Aging and reported that neither sarcopenia nor the components
Body Composition study reported that low quadri- that define weakness increased the risk of hospitalization
ceps strength was associated with increased mortal- or short-term nursing facility stay. A population-based
ity231. Similar results were reported in another study cohort study that defined sarcopenia using the EWGSOP
that showed that reduced leg isometric strength and criteria found an increased incidence of long-term care
increased waist circumference were associated with certification in patients with sarcopenia239. Low muscle
increased mortality232 (HR 2.46, 95% CI 1.34–4.52). mass or strength is causally associated with long-term
These results were further corroborated in the Mini- care placement. The relationship with obesity is clearer,
Finland Health Examination Study, which also showed whereby an elevated BMI is associated with admission
that reduced muscle strength is associated with to a nursing home240. Midlife obesity also increases the
increased mortality (HR 1.30, 95% CI 1.09–1.54)228. Cut- risk of long-term care placement241, an association that
offs specific to individuals from South Korea predicted persists in older adults with obesity242.
higher mortality risk than the FNIH cut-off233. Finally,
a recent meta-analysis found that mortality was high- Treatments for sarcopenic obesity
est in patients with sarcopenic obesity (HR 1.24, 95% Lifestyle interventions, including calorie restriction and
CI 1.12–1.37) compared with healthy individuals, but physical activity, are hallmarks of treating sarcopenic
the authors acknowledged that they had used multiple obesity (Table 2). Few clinical trials specifically focus on
definitions of sarcopenic obesity in their study230. sarcopenic obesity243; however, intentional weight loss in
older adults improves morbidity and physical function186.
Quality of life. Few studies have evaluated the effect of Following a meta-analysis of randomized trials of adults
sarcopenic obesity on quality of life. Sarcopenic obesity with obesity aged ≥55 years, which had follow-up times of
(as defined by low appendicular lean mass normalized for ≥4 years, investigators reported a 16% reduction in mor-
height2 and increased BMI) was associated with unfavour- tality (95% CI 0.71–0.99)243. In the United States, while
able scores on the Medical Outcomes Survey234. Another Medicare covers weight loss therapy244, no major societies
study reported no differences in Short Form-36 scores, outline targeted therapies for sarcopenic obesity187,245.
which provide a measure of quality of life235, between Dennis Villareal’s work best corresponds to partic-
individuals with obesity and low handgrip strength and ipants with sarcopenic obesity as defined by obesity

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a PPT score b FSQ score and motivational interviewing249. Weight loss trials tend
25 ** 16 ** to restrict calories by 500–1,000 kcal per day250. Initial
Change from baseline (%)

***
*** 14 weight loss goals of ~0.5 kg per week can lead to an
20
12 8–10% loss in 6 months, with most patients sustaining
*
15 * 10
* * an 8–10 kg loss in weight during this period of time. We
8 are unaware of specifically tested diets in sarcopenic
10 6
obesity. As in other populations, diets in patients with
4
5
2
sarcopenic obesity lead to weight loss251, with adherence
0 0
to a diet predicting weight loss success252.
Strategies that optimize protein anabolism during
l
ic
ce
ic
ce
n
tro
tro
tio
tio
b
b
an
an
weight loss, such as consumption before exercise or
ro
ro
n
n
na
na
Co
Co
ist
ist
Ae
Ae
bi
bi
s
s
spreading out of protein during the day, can prevent
Re
Re
m
m
Co
Co
c Lean mass d Strength weight loss-induced sarcopenia247,250. Energy deficits
1 25 created by acute calorie restriction could downregu-

*
0
20
**
** late muscle protein synthesis and increase proteolysis,
–1 which contributes to reduced muscle mass247,253,254; how-
–2 15 ever, chronic calorie restriction does not seem to reduce
*
–3 ** 10 muscle protein synthesis, but it might increase it105,255.
**
–4 Increased dietary protein stimulates muscle protein
5
–5
*
synthesis71,256. The source of protein, timing of intake257
–6 0 and specific amino acid constituents can also be factors
in increasing muscle mass and strength. High protein
l
ic
ce
ic
ce
n
ro
ro
tio
tio
b
b
an
an
nt
nt
ro
ro
na
na
intake (1.2 g of protein per kg per day) during weight
Co
ist
Co
ist
Ae
Ae
bi
bi
s
s
Re
Re
m
m
loss might eliminate the beneficial effect of weight loss
Co
Co
Fig. 3 | Mean percentage changes in physical function and lean mass during the on insulin sensitivity in skeletal muscle258. Distributing
weight loss interventions. Measures used included a physical performance test (PPT) protein intake throughout the day259 or pulse feeding at
(scores range from 0 to 36, with higher scores indicating better functional status) (part a); main meals260 could be beneficial for the stimulation of
the Functional Status Questionnaire (FSQ) (scores range from 0 to 36, with higher scores muscle protein synthesis in patients with sarcopenic
indicating better functional status) (part b); lean mass (part c); and strength (measured as obesity.
total one repetition maximum (that is, the total of the maximum weight a participant can The PROT-Age group recommends 1.0–1.1 g/kg
lift, in one attempt, in the bicep curl, bench press, seated row , knee extension, knee protein per day in divided doses, acknowledging
flexion and leg press)) (part d). Scores on the PPT were used as an objective measure that a ‘one size fits all protein recommendation’ fails
of frailty (primary outcome), and scores on the FSQ were used as a subjective measure of
to account for the complex physiological changes of
frailty. Percentage changes are presented as least-squares–adjusted means; T bars
indicate standard errors. *P < 0.05 for the comparison with the control group. **P < 0.05 ageing71. Generally, 25.0–30.0 g of protein contain-
for the comparison with the aerobic group. ***P < 0.05 for the comparison with the ing 2.5–2.8 g of leucine can slow frailty 261,262. Early
resistance group. Figure adapted with permission from ref.247, New England Journal of pilot studies demonstrate that meals enhanced with
Medicine, Villareal, D. T. et al. Aerobic or resistance exercise, or both in dieting obese protein and coupled with a weight loss intervention
older adults, 376, 1943–1955 Copyright © (2017) Massachusetts Medical Society. improve physical function 263. For example, a high-
Reprinted with permission. protein diet in conjunction with resistance training
preserved appendicular lean mass during weight loss264.
In a pilot study, participants with sarcopenic obesity
with evidence of physical frailty246,247. In this cohort of undergoing a weight loss programme augmented by
patients, weight loss alone or exercise alone improved a high-protein diet showed improvements in muscle
physical function; however, a combination of weight strength and Short Form-36 scores (ref.265). We need
loss and regular exercise improved physical function further evidence to support the effect of supplemental
and ameliorated frailty more than either intervention protein on functional outcomes in patients with sar-
alone246. Moreover, another study reported that weight copenic obesity266–268. High-protein diets consisting
loss plus combined aerobic and resistance exercise was of 1.0–1.2 g per kg per day should be prescribed with
the most effective method for improving functional caution to prevent renal dysfunction269 as evidenced by
status of adults aged 65 years and older with obesity247 observational data270–272, as higher doses have recently
(Fig. 3). Hung‐Ting Chen and colleagues248 evaluated four demonstrated no changes in lean mass273. We recom-
groups of individuals with sarcopenic obesity according mend the importance of ensuring adequate protein
to different exercise interventions (aerobic, resistance, intake in countering weight loss-induced sarcopenia
combined aerobic and resistance), and controls who in individuals with sarcopenic obesity participating in
were prohibited from engaging in exercise, and demon- programmes. Careful medical monitoring and dietary
strated that individuals in the resistance training group planning are required when optimizing protein intake
had the greatest improvements in strength. while limiting calorie restriction, and this often needs
to be administered under the auspices of a registered
Dietary strategies: calorie restriction and protein dietician with expertise in this population. The chal-
supplementation. Dieticians are multidisciplinary team lenges in limiting calories are recognized, and hence we
members integral to developing lifestyle interventions believe that alternative approaches are crucially needed
whose delivery is often grounded in behavioural theories to augment muscle mass and strength.
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Resistance training and aerobic exercise. Several pro- hypertrophy group or a high-speed circuit group for
fessional societies3,187,245,274 recommend that all older 15 weeks289. High-speed circuit training was associated
adults engage in at least 150 min per week of moderate with nonsignificant improvements between groups in
to vigorous aerobic exercise, with two sessions of resist- short performance physical battery (mean difference 1.1,
ance exercises consisting of strength training, flexibility 95% CI –0.1 to 2.4; P = 0.08) and power (mean difference
and balance. Aerobic exercise and resistance training are 158 W, 95% CI 2–315; P = 0.01). We note that while these
safe, even in patients who are at a high risk of falling275. trials enrolled patients with sarcopenic obesity in each
Aerobic exercise improves cardiorespiratory fitness and arm, they are small, short-term studies.
has beneficial effects on mortality276–278. Even mini- Other exercise therapies, including tai chi or yoga,
mal resistance exercise improves muscle strength and could potentially be beneficial; however, to our knowl-
mass279,280, and progressive resistance exercises counter edge, no studies have evaluated these modalities in
sarcopenia by increasing strength. As with any exercise sarcopenic obesity. Tai chi and The Otago Exercise
programme, clinical consultation and medical clearance Programme (a home-based balance and strength fall
is advised. prevention programme) have been shown to be effec-
A Cochrane review reporting physical outcomes of tive at preventing falls and improving physical function,
progressive resistance exercises for older people identi- mobility and functional measures of lower extremity
fied 33 trials that significantly improved physical abilities strength in older adults291. A meta-analysis of 18 trials
(standardized mean difference 0.14, 95% CI 0.05–0.22) in (n = 3,824), including study participants greater than
2,172 participants, with improvements in muscle strength 65 years who participated in tai chi for a minimum of
(standardized mean difference 0.84, 95% CI 0.67–1.00) in 4 weeks (range 1–12 months) 1–3 times per week,
73 trials281 (3,059 participants). The LIFE study282, a struc- demonstrated a reduction in falls of 20% (relative
tured, moderate-intensity physical activity programme, risk (RR) 0.8, 95% CI 0.72–0.88)292. In addition, yoga
demonstrated reduced persistent mobility disability has been shown to improve mobility in participants
(HR 0.72, 95% CI 0.57–0.91) compared with a health 60 years of age and older, with no restriction on their char-
education programme. Evaluation of four groups of men acteristics, whose follow-up ranged from 8 to 24 weeks
and women aged 60–75 years with sarcopenia demon- (total duration 8–36 hours of yoga)293. A meta-analysis
strated that 2 days of high-resistance concentric exercise of 28 studies demonstrated a positive effect of aquatic
with one bout of low-resistance exercise increased muscle exercises on physical functioning (RR 0.70, 95%
expression of pro-inflammatory cytokine receptors, max- CI 0.48–0.92) compared with no training (control
imized muscle mass and total lean mass and improved group)294. Furthermore, the data suggested that aquatic
knee extension283. A secondary subset analysis of the LIFE exercises are as effective as land-based exercises (stand-
pilot study found that the short physical performance ardized mean difference 0.39, 95% CI 0.12–0.66). Finally,
battery — an objective assessment tool for the evaluation while training until failure might be an approach for
of lower extremity function (higher score equals better muscle strengthening and endurance295, we generally
function)284 — of patients with sarcopenia improved recommend exercising until fatigue rather than fail-
from 7.4 to 8.7 when compared with the successful ageing ure, as exercising until failure can increase the risk of
group285. Although the LIFE study is considered a stand- musculoskeletal injury.
ard for physical activity in older adults282, we acknowledge We advocate individualized exercise treatment for
its lack of evidence in sarcopenic obesity and the lack of patients with sarcopenic obesity because of the associ-
power in this pilot trial. ated medical comorbidity and disability. As previously
High-intensity resistance training combined with described, the exercise programme296 should begin at
short resting intervals improves body composition, a fairly low-to-moderate intensity, duration and fre-
muscle and functional performance in men aged quency to minimize injury and maximize adherence;
68 ± 4.1 years286. High-speed resistance training over this approach progressively induces exercise adapta-
12 weeks induced greater improvements in muscle power tions246,247. Aerobic activity should target ~65% of the
and functional capacity than low-speed training287. In this peak heart rate, aiming to reach 70–85% of peak heart
study of 60 women of Hispanic descent aged over 60 years, rate over the duration of the exercise regimen. Resistance
high-speed training consisted of individuals performing activities, on the other hand, should focus on 1–2 sets of
exercises as fast as possible (1 second or less) and was 8–12 repetitions at ~65% of one repetition maximum,
compared with low-speed resistance training (3 seconds). which is defined as the maximal amount of force a
The authors of this study also demonstrated that two person generates in a single repetition, with the aim of
versus three training sessions per week for 12 weeks of advancing to a goal of 2–3 sets of 75% of one repetition
high-speed resistance training were equally effective for maximum over time. These activities are recommended
improving physical performance and quality of life288. even for frail, older adults246,247.
High-velocity knee extension training at 240° of move-
ment per second increases the expression of MYH6 and Calorie restriction and physical activity. A trial of older
MYH9 mRNA and improves muscle enhancement138. adults with obesity247 consisted of a hypocaloric diet with
The effect of power training (moving resistance at an energy deficit of 500–750 kcal per day on average, 1 g
higher speed) on function requires further investi- high-quality protein, plus either 60 min of progressive
gation289,290. A pilot study of patients with sarcopenic aerobic exercise and resistance training or 75–90 min
obesity (defined using EWGSOP criteria for sarcopenia of both aerobic exercise and resistance training, three
and BMI for obesity) were randomized to a strength and times a week. The findings demonstrated increases in

Reviews
physical performance test scores (higher score equals serum concentrations of adiponectin (6.9 μg/ml for
higher level of function), more so in the combined aer- individuals in the group without aerobic activity versus
obic and resistance exercise group (27.9 to 33.4 points 8.5 μg/ml for individuals in the group with aerobic
(21% increase)) than in the aerobic (29.3 to 33.2 points activity (P < 0.001))305. Levels of adiponectin were also
(14% increase)) or resistance group (28.8 to 32.7 points elevated following a multicomponent, randomized life-
(14% increase)) alone. Other activities for weight loss style intervention study that investigated the mRNA
therapy in older adults reflect similar components and expression of adiponectin and its receptor in skeletal
outcomes and have produced similar findings250,297. muscle in adults with impaired glucose tolerance who
There are few multicomponent studies in patients with were aged ≥60 years and had a BMI of 30–40 kg/m2
sarcopenic obesity. A meta-analysis showed that aerobic (ref.306). These data suggest that improved insulin sen-
exercise and resistance were useful tools to preserve fat- sitivity is due, in part, to the distribution of adiponectin
free mass in adults aged ≥50 years who were engaged in across various tissues and an upregulation in the expres-
a moderate energy restriction-induced weight loss pro- sion of its receptor. Other conflicting data suggest that
gramme298. Increased muscle mass and reduced total and in patients with knee osteoarthritis, weight training
visceral fat over an 8-week intervention were observed in combined with walking three times a week for 1 hour
predominantly female individuals, whose mean age was does not have any significant effect on levels of TNF,
69 years, with sarcopenic obesity engaged in resistance IL-6 or C-reactive protein307. The addition of weight loss
training248. A resistance programme of participants ful- of 0.3 kg per week for 6 months to physical activity in
filling the EWGSOP criteria for sarcopenia and obesity older community-dwelling adults with obesity or over-
as defined by percentage body fat demonstrated reduced weight results in a greater reduction in serum levels of
rates of sarcopenia and improved physical function fol- leptin and IL-6 than either physical activity alone or a
lowing three training sessions weekly over a 12-week successful ageing health education intervention308.
period compared with a control group receiving no
intervention297. A combined treatment of diet and exer- Risks of weight loss in older adults
cise improved physical function in frail older men with Energy restriction with a hypocaloric diet with or without
obesity aged ≥65 years for 1 year, despite resulting in a exercise results in the loss of approximately one-quarter of
reduction in oestradiol levels and only a modest increase lean mass per unit weight, which could worsen sarcopenia
in testosterone levels299. and osteopenia154. A total of 33 intervention studies lasting
Combining both diet and exercise can positively 8–24 weeks reported that unopposed calorie restriction
improve adipose markers of adiponectin and signif- without resistance training leads to the loss of muscle mass
icantly reduce leptin levels. In response to a 6-month and loss of handgrip strength of up to 4.6% and 1.7 kg,
randomized diet and exercise intervention, levels of respectively309. Unopposed diet therapy without exercise in
C-reactive protein and IL-6 decreased in older adults older frail adults ≥65 years with obesity (BMI ≥30 kg/m2)
(age ≥65 years) with obesity (BMI ≥30 kg/m2) com- led to a marked loss of lean mass at 6 months and 1 year
pared with controls (−2.5 versus 0.8 mg/l (P < 0.05) and (−3.5 kg and −3.2 kg, respectively) compared with the diet
−2.4 versus 1.6 pg/ml (P < 0.05), respectively)300. Yet, the and exercise group, where the loss of lean mass was par-
positive effects on circulating cytokines, adiponectin tially mitigated (−1.7 kg and −1.8 kg, respectively)246. In the
and TNF were due to diet and not exercise301, which is Look AHEAD trial, total skeletal mass decreased in both
consistent with the direct effect of exercise on or within of the intensive lifestyle groups and in the diabetes support
muscle not being reflected in the circulation 133,134. and education group (−1.4 kg; P < 0.001). The researchers
A study that investigated the effect of diet or diet and reported that patients in the intervention group regained
exercise interventions in individuals aged 50–79 years appendicular lean mass during the second year and that
with overweight or obesity reported that levels of adipo weight loss was 5.2 kg less in the intervention group than
nectin increased in individuals with overweight or in participants in the control group, whose weight did
obesity compared with controls (diet resulted in 9.5% not markedly change after the second year310. A review of
increase in adiponectin (P < 0.001), and diet and exercise 52 studies reported that loss of fat-free mass as a propor-
resulted in a 6.6% increase in adiponectin (P < 0.001)). tion of overall weight was attenuated after combining
Furthermore, levels of leptin in individuals with obesity exercise with calorie restriction298.
or overweight decreased by 27.1% in the diet group and Weight loss in younger adults (age 45–65 years) led to
40.1% in the diet and exercise group302. loss of lean mass after calorie restriction (4% reduction
Investigators in the LIFE pilot study reported that in lean mass; P < 0.0001), which was partially lessened by
individuals in the physical activity group had reductions augmentation with aerobic activity (2% reduction in lean
in IL-8 but no differences in other inflammatory mass in participants who had augmented weight loss
markers 303. A 12-week aerobic exercise regime in with aerobic activity; P = 0.05)311. One study evaluated
combination with a low glycaemic index diet or high the effectiveness of low-fat diets versus carbohydrate-
glycaemic index diet resulted in reductions in leptin lev- restricted diets with or without progressive resistance
els in two groups of participants who had elevated levels exercise on fat-free mass in 42 men with the metabolic
of adiponectin, suggesting that the reductions in leptin syndrome whose age was 59 ± 7 years. Percent weight
were a result of exercise training and independent of loss from appendicular lean mass dropped markedly
dietary glycaemic index304. Another study reported that more in the low-fat and no exercise group than in the
in postmenopausal women with overweight or obesity, other groups, suggesting that this intervention has a
adding aerobic activity to calorie restriction increased detrimental effect on appendicular lean mass312.
Reviews
Obesity is inversely related to BMD and fractures313 function331 and proximal muscle weakness332 through the
but might increase the fracture risk through bone actions of vitamin D metabolites333. Vitamin D deficiency
quality314,315 or frailty132,316 independent of BMD. Adipose is associated with an increased risk of falls and fractures,
tissue has been shown to be inversely associated with bone and reduced muscle mass and strength334–338, independ-
material strength and positively associated with cortical ent of obesity. We agree with the American Geriatrics
porosity, indicating an adverse effect of adipose tissue on Society recommendation of 1,000 IU of vitamin D3 per
bone microstructure317. Calorie restriction alters bone day with calcium among non-institutionalized adults
metabolism, resulting in the loss of BMD in the hip with- aged ≥65 years334, to maintain serum levels of vitamin D
out effects on lumbar spine318, even after a 4-month restric- at ≥30 ng/ml.
tion319. Increases in bone markers such as osteocalcin
and of carboxy-terminal telopeptide (C-telopeptide) and Future directions and emerging therapies
N-terminal telopeptide (N-telopeptide) of type I collagen We anticipate that a deeper understanding of sarcopenic
were observed. Levels of osteocalcin were increased in obesity will emerge over the next decade, which will ulti-
the diet-only group (36 ± 11.6%), yet its levels were no mately bridge the divide between clinical practice and
different than baseline in individuals on diet coupled research. Here, we outline the major gaps of knowledge
with exercise; increased differences were reported in and advancements needed to further the field (Box 1).
the disposition index (an index of insulin secretion after
correction for insulin resistance) in the diet–exercise Harmonizing a definition. The most notable barrier
group (92.4 ± 11.4%) compared with the diet-only group to advancing the science in targeting this condition is
(61.9 ± 15.3%) at 12 months320. Loss of BMD in older the lack of a consistent definition for sarcopenic obesity.
adults with obesity seems to continue during long-term While the criteria for identifying and classifying subcu-
lifestyle change in the opposite direction to the weight taneous or visceral adiposity are somewhat consistent,
changes321. These findings suggest that BMD and markers major progress is needed regarding the definition of
of bone turnover following long-term calorie restriction sarcopenia. Advancing our understanding of the rel-
show larger changes in patients than in healthy control ative contributions of strength and muscle mass — as
participants advised to continue their current diet322. well as their differences — might help. The introduction
In one study, the authors reported that trabecular in 2016 of an International Classification of Diseases 10
bone microarchitecture was no different in calorie- code for sarcopenia (M62.84) will permit clinical recog-
restricted participants (~35% less calories than controls) nition and promote its diagnosis, classification and drug
than in middle-aged individuals eating a Western diet323. development339,340. Different populations, ethnicities and
Furthermore, trabecular geometry, cortical geometry sexes require specific diagnostic thresholds; therefore,
and strength were no different in individuals under integrating highly accurate body composition measures
going intentional weight loss through calorie restriction into clinical settings will encourage clinical identifica-
or weight maintenance for 6 months324, which suggests tion of sarcopenic obesity. The disparate classification
that calorie restriction has protective effects on bone has impeded progress in this field.
quality. However, 2017 data from the Look AHEAD trial
showed that long-term intentional weight loss was asso- Integrating methods for analysing body composition
ciated with a 39% increased risk of fragility fractures325. into clinical practice. To promote the translation of
Very-low energy or protein-sparing diets to induce rapid methods for assessing body composition, including CT,
weight loss are not recommended owing to potential loss MRI and DXA, into routine care, we acknowledge the
of muscle mass, strength and bone and risks of dramatic need to remove regulatory and operational obstacles,
fluid, electrolyte and water shifts owing to protein shifts; particularly in the United States. For instance, DXA is
however, a preliminary, short-term study in a popula- routinely performed for screening and assessment of
tion of individuals ≥65 years of age suggests potential osteoporosis and is generally covered by insurance for
benefits326. Studies emphasize exercise training during this indication341. Older adults often receive gold stand-
calorie restriction to prevent an increase in bone turn- ard imaging, which can accurately ascertain muscle and
over327 and an increase in serum levels of sclerostin328, fat content, for indications other than sarcopenic obe-
thus minimizing bone loss. Whether weight loss and sity, such as abdominal pain or back pain342,343. Assessing
exercise lower overall risk of falls and fractures despite muscle strength (using handgrip dynamometry) and
the decline in BMD is unknown, suggesting the need for muscle mass (using DXA, bioelectrical impedance or
formal evaluation in future studies. other modalities) can fill a clinical gap in identifying
sarcopenic obesity. Widespread availability of DXA
Supplementation with calcium and vitamin D. even in low-resource areas344 permits this evaluation.
Conventional strategies to minimize the effect of weight Future studies should focus on dissemination and
loss on bone metabolism, including up to 1,200 mg sup- implementation strategies of using such diagnostics.
plemental calcium per day and 800–1,000 international
units (IU) per day of vitamin D3, are needed to minimize Epidemiology and clinical outcomes. Further work is
the risk of weight loss-induced BMD reduction329. Oral required to elucidate the descriptive epidemiology of sar-
calcium should be coupled with vitamin D to mitigate copenic obesity regarding important outcomes beyond
the potential risks of unopposed supplementation330. weight loss, comorbidity and mortality. Though experts
Supplementing vitamin D in patients with sarcopenic currently debate a unifying definition, one will ulti-
obesity can potentially influence and improve muscle mately become accepted, standardized and implemented.

Reviews
Box 1 | Emerging therapies in sarcopenic obesity differentially affect muscle mass, strength and weight.
Research should distinguish appropriate diets, the type of
Anamorelin protein to administer (such as whey or casein) and poten-
A ghrelin analogue used in cancer cachexia that could promote appetite and enhance tially the timing of intake in relation to exercise, as well
lean mass with anti-inflammatory and anabolic properties.
as whether recommendations should be based on ideal
Bariatric surgery or total body weight. The specific composition of essen-
The safety and efficacy of different procedures (Roux-en-Y, gastric band and gastric tial amino acids (for example, leucine or creatine) and
sleeve) are currently unknown but can be considered in carefully selected older adults vitamin D supplementation requires structured interven-
aged 65 years and older. tions to ascertain dosing and monitoring. For instance,
Mesenchymal stem cells leucine-rich protein can activate metabolic pathways
Shared precursors of muscle, bone and cartilage that hold promise in the regeneration involved in testosterone and IGF1 homeostasis348–351.
of muscle tissue. Barriers exist but these cells may play a promising role in the future Such elements will allow tailored dietary interventions.
management of sarcopenia.
Myostatin inhibitors Exercise and combined interventions. While aero-
A treatment type with biological plausibility for improving physical function by enhancing bic and resistance exercises are core components in
skeletal muscle growth development. This class of therapy can directly inhibit muscle loss, the treatment of sarcopenic obesity, the specific fre-
with data suggesting improvements in physical function in patients with cancer. quency, intensity, time and types (aerobic, resistance
neuromuscular activation or both) should be considered. The relationship of
Whole-body vibration therapy (using electrical stimuli) or tai chi can enhance muscle resistance exercises with respect to dietary composi-
contraction efficiency and function. tion requires evaluation. Longitudinal studies should
Periodization strategies verify whether weight loss plus combined aerobic and
Systematic variation in training specificity, intensity and volume used in sports resistance training prolongs physical independence in
programmes to achieve peak physical performance. May be feasibly prescribed in sarcopenic obesity. Such studies might translate to older
sedentary, frail, older adults to improve function but it is premature to endorse these adults who have access to health membership benefits in
strategies. community-based exercise centres352. Assessing aquatic
Testosterone and selective androgen receptor modulators therapies353–355 or tai chi356, in isolation or in tandem with
Important regulators of body composition that increase muscle and bone mass by other types of physical activities, might prove useful for
increasing insulin-like growth factor 1 (IGF1) and decreasing inflammatory markers. treating patients with sarcopenic obesity. The addition
Data on their impact on muscle strength and function are conflicting. Selective androgen of pharmacotherapy, such as testosterone supplementa-
receptor modulators (that is, enobosarm) preferentially target androgen receptors on tion, to progressive resistance training augmented the
muscle and bone, sparing the androgenic impact elsewhere in the body. Early efficacy
improvements in body composition, including reduced
studies demonstrate improved lean mass and function in patients with cancer.
fat mass and improved lean mass357. However, whether
Weight loss therapies or not physical activity should be combined with novel
Anti-obesity medications (liraglutide, lorcaserin, phentermine, topiramate, bupropion and promising treatments requires systematic and
and orlistat) are approved for use in non-geriatric populations with weight loss as an
further investigation.
indication. Their use is restricted to off-label use for weight loss, and few data exist on
their safety and efficacy in this population.
Periodization strategies. Periodization, which is a
Vitamin K systematic variation in physical training specificity,
Inhibits bone resorption and osteoclast formation and may be helpful in mitigating intensity and volume within periods, has emerged as
bone loss following intentional weight loss. Supplementation may increase bone
a potential strategy to improve muscle performance358.
resorption markers, although conflictive data exist on its effect on BMD and fractures.
Periodization is typically used in sports programmes
aiming to achieve peak physical performance while min-
Until then, useful and cost-effective measures, including imizing overtraining risk. Linear periodization reduces
grip strength, gait speed, the short performance physical training volume while increasing training intensity or
battery and/or bioelectrical impedance or DXA, should load between cycles359. Periodized resistance training
continue to be used in clinical and research arenas345–347. in older adults demonstrated equal efficacy in physical
Focusing on patient-centred outcomes, including phys- function and physiological outcomes when compared
ical function and quality of life, is important. Additional with non-periodized resistance training360. In patients with
trials in sarcopenic obesity can clarify the mechanisms sarcopenic obesity (defined using handgrip strength and
underlying interactions between fat, muscle and bone that BMI), no differences were observed in strength, power or
explain alterations in short-term and long-term outcomes. short performance physical battery following a 10-week
Improved characterization of biological signalling will per- periodization strategy of strength and endurance
mit full comprehension of the differences between sarcope- training with concentric and eccentric movements290.
nia and sarcopenic obesity. The association of resource and Preliminary studies indicate that periodization results
cost data in health systems and third-party payers (insurers) in increases in serum levels of irisin and decreases in
will escalate the importance of sarcopenic obesity. IL-1β361. Leptin might also be reduced further with peri-
odized resistance training362. While periodization could
Dietary composition and restriction. No specific inter- feasibly be prescribed in sedentary or frail older adults
ventions have tested diets for the treatment of sarcopenic to improve physical function, it is premature to endorse
obesity. While diets should be individualized, the com- this training as superior to non-periodized training358.
position of carbohydrates, fats and protein have differed Longer-term investigations in older populations with
in clinical trials. Adjusting these components might sarcopenic obesity are needed.
Reviews
Skeletal muscle index

Whole-body vibration therapy. Whole-body vibration but minimally changes lean mass389–391. In carefully
Absolute muscle mass (in kg) therapy is a novel therapy that could increase muscle selected individuals, industry-sponsored trials should
normalized for height (muscle contraction efficiency and function with similar effi- evaluate these agents in both older adults with obesity
mass in kg divided by height cacy to resistance training, though data on its efficacy and patients with sarcopenic obesity.
(in m)).
are mixed. This safe and convenient technique is asso-
Absolute muscle mass ciated with a low risk of injury363,364. Whole-body vibra- Bariatric surgery. Bariatric surgery improves weight and
Muscle mass consisting of all tion therapy uses the transmission of mechanical stimuli metabolic outcomes and reduces mortality. In carefully
limbs and muscle from visceral through the person’s body365,366 to activate the primary selected patients, this could be considered a treatment for
organs.
ends of muscle spindles, which leads to neuromuscular sarcopenic obesity in older adults ≥65 years392. Its safety
activation367–369. The participant stands on a vibrating and efficacy in sarcopenic obesity is unknown other than
platform where electrical signals are delivered through one study that evaluated the influence of sarcopenic obe-
the body, and thus primary endings of muscle spindles sity on gastric bypass and sleeve gastrectomy results393.
are activated. The population of participants had a mean age of
Hengting Chen and colleagues370 identified 10 rand- 44 years, and no documented differences were observed
omized trials of whole-body vibration therapy showing in weight loss results or comorbidity resolution. Bariatric
its usefulness in younger adults (difference (d) = 0.35 surgery leads to loss of fat mass394, alters gut hormones395
(95% CI 0.05–0.64; P = 0.02)), but this usefulness was and can exacerbate weight loss-induced sarcopenia396–398
not seen in older adults (d = −0.04 (95% CI −0.28 to and osteoporosis399–402. Carefully designed studies are
0.21; P = 0.78)). The review included heterogeneous needed before promoting this intervention.
studies using different methodologies, training and
vibration characteristics. Separately, Ricky Lau and col- Testosterone. Obesity negatively affects serum levels of
leagues371 reviewed 13 trials of older adults and found testosterone and disrupts the actions of testosterone by
significant treatment effects on knee extension dynamic increasing its aromatization to oestrogen403 and down-
strength (d = 0.63; P = 0.006), isometric strength regulating follicle-stimulating hormone and luteiniz-
(d = 0.57; P = 0.003) and functional measures such as ing hormone404, thus exacerbating hypogonadotropic
sit-to-stand (d = 0.72; P < 0.001). Whole-body vibra- hypogonadism. Testosterone is an important regulator
tion therapy was as efficient as a fitness programme at of body composition with ageing, as it increases mus-
increasing knee extension and lower leg muscle mass in cle and bone mass, increases IGF1 levels, decreases
non-institutionalized men aged 60–80 years old372 and inflammatory markers405 and alters biomarkers of bone
improved quality of life and functional measures373. turnover in adults with hypogonadism. Testosterone
Summative effects of the combination of whole- deficiency can impair muscle adaptation to exercise
body vibration therapy and resistance exercises374–377 or owing to reduced expression of IGF1 and increased
of whole-body vibration therapy and vitamin D367 are inflammatory cytokines. However, reductions in TNF
mixed. Others hypothesize that pathways contributing and IL-6 observed in older men with hypogonadism can
to weight loss as a result of whole-body vibration ther- be reversed following testosterone treatment406.
apy could inhibit adipogenesis, increase energy expend- Supplementation with testosterone promotes IGF1
iture and reduce muscle mass378. Augmenting existing mRNA and protein expression, leading to increased
squatting exercises with whole-body vibration therapy lean mass through increased muscle protein synthesis52.
failed to improve muscle mass in younger men aged Increases in IGF1 following testosterone administration
18–30 years379. Future research should focus on type, might improve muscle mass and strength enhanced by
frequency and duration of treatment380. exercise52,56,406, and in men over 60 years with low tes-
tosterone, gains in lean mass following testosterone
Weight loss medications. None of the six FDA-approved supplementation ranged from 1.6 kg to 6.20 kg (ref.407).
medications for weight loss are approved for use in older Androgen therapy also reduces fat mass (−1.78%).
adults aged over 65 years, and few have been evalu- Therapy with testosterone and GH in older men aged
ated in terms of changes in body composition. In nine 65–80 years with normal testosterone levels resulted in
older adults prescribed liraglutide, a weight decrease greater improvements in lean mass with both treatments
of 2.0 kg (−1.5 kg fat mass and −0.9% android fat) was than with either alone56,408. In select older men over the
observed, with a marginal improvement of 0.03 kg/m2 in age of 60 years with testosterone deficiency and frailty,
skeletal muscle index (absolute muscle mass normalized by body composition and quality of life improved following
height squared)381. Lorcaserin leads to more fat loss than supplementation with testosterone409–411. Three years of
placebo in patients with diabetes mellitus (−12.1% versus testosterone administration in patients with low levels
−5.9%; P = 0.008) and more trunk obesity (3.65% versus of testosterone resulted in an increase in lean mass
−0.36%). When compared with controls, patients treated (0.9 kg, 95% CI 0.5–1.4; P < 0.001)412. Testosterone
with lorcaserin had greater fat mass loss than lean mass deficiency and treatment in older men have been
loss382. Topiramate negatively affects BMD383 but might reviewed elsewere413.
not affect lean mass384,385. Phentermine minimally alters There are conflicting data on the effect of
lean mass386. Bupropion can blunt olanzapine-associated testosterone supplementation on muscle strength and
weight gain without affecting bone metabolism387 and function50,51,357,414. In the ‘Testosterone Trials’, treatment
in combination with naltrexone can lead to a reduction in with testosterone improved participants’ results in the
fat mass without altering lean mass388. Orlistat promotes 6 min walk test compared with placebo (20.5% versus
the weight loss via fat and visceral adipose tissue loss 12.6%; P = 0.003)53. Elsewhere, testosterone-associated

Reviews
increases in lean mass were accompanied by improve- fibroblasts426. Enobosarm, a non-steroidal SARM, suc-
ments in handgrip strength, knee extension and leg cessfully increased muscle mass and physical function
press and chest press exercises415,416. A meta-analysis of in patients without cancer and in those with advanced
testosterone supplementation found effect sizes of 0.47 lung, colorectal or breast cancer or lymphoma427–429.
(95% CI 0.12–0.84) for upper and 0.63 (95% CI 0.03– Other studies showed increases in lean mass without
1.28) for lower extremity strength417, without sustained improvements in strength or physical performance in
improvements in body composition418. Healthy men patients with sarcopenia428,430. Early trials demonstrated
with reduced levels of testosterone had no improvements a greater total lean mass of 1.3 kg (P < 0.001), better
in muscle strength or mobility after 6 months of sup- physical function as measured by reduced stair climb
plementation350. Another trial of testosterone treatment time (P = 0.013), a trend towards lower blood levels of
found improved stair-climbing power and strength351. glucose of 6.9 ± 2.5 mg/dl (P = 0.052) and lower insulin
Improvements in lean mass do not directly result in sensitivity (−27.5% versus 2.6%; P = 0.013) with 3 mg
improved function after testosterone therapy409. With per day of GTx-024 (an orally bioavailable nonsteroidal
ageing, muscle strength often drops before muscle SARM) than with placebo 429. Enobosarm signifi-
mass73. The nonlinear relationship between mass and cantly increased lean mass compared with baseline
function suggests that hypertrophy rather than muscle (1.0 kg, 95% CI −4.8 to 11.5; P = 0.046) versus controls
fibre hyperplasia materializes without neuronal plas- (0.02 kg, 95% CI −5.8 to 6.7; P = 0.88). SARM treatment
ticity. A reason for the observed significance in some in older women with low lean mass, a self-reported
studies might be a patient’s intrinsic threshold for func- mobility disability and a short physical performance
tional impairment. Frail older adults with testosterone battery score between 4 and 9 provided improvements
deficiency could require minimal incremental gains in in muscle mass without benefits of improved strength430.
mass to realize benefit. Therefore, we suggest an individ- SARMs that have been developed in the past 5 years
ualized approach. Comorbidity and health status, small have not demonstrated adverse effects431 and have
sample sizes, minimal changes in testosterone levels fol- restored cortical and trabecular bone in orchidecto-
lowing treatment and the lack of practice sessions before mized mice432. Transdermal SARMs could emerge in
initiating strength testing could have contributed to the the future433. A review of SARMs has been conducted
negative findings. Areas of future research should iden- elsewhere434, but they could be of benefit to patients with
tify responders to androgen supplementation in those sarcopenic obesity who require muscle mass improve-
with low lean mass or strength. ments rather than strength. However, conclusive
Testosterone potentially augments diet-induced loss evidence is still needed.
of fat mass in individuals with BMI ≥30 kg/m2 and low
testosterone levels. Over 56 weeks, testosterone-treated
Anamorelin. Anamorelin, an oral ghrelin analogue, is
participants (mean age 53 years) had greater reductions effective for improving appetite in patients with cancer
in fat mass (mean between-group difference 2.9 kg; cachexia and might hold promise in patients with
P = 0.04) and visceral fat (−2,678 mm2; P = 0.04) than sarcopenic obesity. Its anti-inflammatory and anabolic
controls. Testosterone-treated participants also had properties might counter the negative nitrogen balance
greater lean mass regain during weight maintenance observed in sarcopenia. Anamorelin is safe, well toler-
(mean between-group difference 3.4 kg; P = 0.002) fol- ated and stimulates appetite by promoting expression of
lowing the very-low-energy diet, suggesting that weightGH, IGF1 and IGF-binding protein 3 (refs435,436), which
loss was exclusively fat mass419. As multicomponent reverses muscle atrophy in mice437. A meta-analysis of
interventions can attenuate lean mass losses, studies 1,641 patients with cancer demonstrated improved total
should evaluate whether testosterone replacement helps body weight, lean mass and quality of life (1.78, 95% CI
preserve muscle and bone mass during weight loss in 1.28–2.28, P < 0.001; 1.10, 95% CI 0.35–1.85, P = 0.004;
patients with sarcopenic obesity. 0.19, 95% CI 0.08–0.30, P = 0.0006, respectively)438.
Adverse events associated with testosterone supple- A review of four studies demonstrated high hetero-
mentation include polycythemia420, possible cardio geneity with improved symptom scores, and in three
vascular events421, venous thromboembolism422 and studies, improved lean mass was shown439. Anamorelin
prostatism423. Those who favour supplementation cite improved lean mass in patients with cancer cachexia
a lack of credible evidence related to cardiovascular compared with placebo (2.09 kg, 95% CI 0.94–3.25;
risk424. Future cost–benefit analyses should compare theP = 0.0006)440 but failed to improve muscle power or
relative benefits regarding body and bone composition handgrip strength in patients with inoperable non-
with disability risk. To date, the American Association small-cell lung cancer441. Lack of functional improve-
of Clinical Endocrinologists187, the Endocrine Society425
ments were also observed in patients with unresectable
and the Obesity Society186 have not recommended tes- non-small-cell lung cancer442. Adverse effects are no
tosterone supplementation as a treatment for sarcopenia different than with placebo. It is unclear whether the
or obesity. improved lean mass observed in patients treated with
anamorelin has differential effects on intramuscular fat
Selective androgen receptor modulators. Selective in patients with sarcopenic obesity. As no studies have
androgen receptor modulators (SARMs) target androgen established improved function or strength, further eval-
receptors on muscle and bone but do not activate andro- uation is needed, particularly in the subset of patients
genic effects elsewhere. SARMs indirectly affect non- with sarcopenic obesity who have low lean mass with
muscle androgen receptor pathways mediated by muscle intact muscle strength.
Reviews
Myostatin inhibitors. Individuals with sarcopenia have of the complex relationship between vitamin K and
elevated levels of myostatin443, a negative regulator of weight loss-induced effects on bone, muscle and fat in
skeletal muscle growth development444. Myostatin is sarcopenic obesity is currently in its infancy465.
also expressed in adipose tissue and is inversely related
to insulin resistance445. In vitro trials demonstrate Mesenchymal stem cells. Muscle, bone and cartilage
that myostatin inhibitors increase muscle mass and derived from mesenchymal cells share common precur-
strength446, suppress irisin, downregulate inflammatory sor mesenchymal stem cells. In mice, transplantation of
cytokines and improve insulin resistance447. Its expres- satellite cells into damaged muscle leads to self-renewal
sion drops following weight loss because it directly influ- and muscle regeneration466,467. An early human study
ences adipocyte metabolism448, and myostatin inhibitors suggests a role for mesenchymal stem cells in managing
can directly inhibit muscle loss. Myostatin inhibitors frailty468. The cost, regulatory constraints and potential
reduce expression of myostatin in both aerobic and ethical barriers of applying such technology into clinical
resistance exercise449 and might be beneficial in treating settings need to be addressed further.
sarcopenic obesity. Early data suggest improved physical
function in patients with non-small-cell lung cancer427. Conclusions
Interventions should directly measure changes in levels The growing challenges associated with sarcopenic obe-
of myostatin and corresponding changes in muscle mass, sity will probably worsen with the changing demographic
strength, function and insulin sensitivity. distribution of our ageing population. Effective evidence-
based therapies can be helpful for improving physical
Vitamin K. Vitamin K might have a role in mitigating function in older adults. We encourage further agree-
bone loss following intentional weight loss by inhibit- ment on defining sarcopenic obesity within both research
ing bone resorption450 and osteoclast formation451. Its and clinical settings. In our opinion, a lack of a consensus
deficiency has been associated with increased risk of definition is one of the greatest limitations to advancing
fragility fractures452–455, particularly in patients who the science. Without being able to accurately identify
are malnourished456,457. Vitamin K supplementation populations of patients, there will be continued difficul-
can restore serum levels of the vitamin458,459 and might ties in targeting further obesity subtypes. Clarifying the
increase bone resorption markers460. Conflicting data mechanisms that contribute to sarcopenic obesity might
exist; in some studies, vitamin K antagonists demon- elucidate novel therapies to improve function, quality of
strate no differences in BMD or fracture rates461, while life and prevent institutionalization. A number of novel
other data suggest lessening of steroid-induced BMD462 therapies independently hold promise or could be con-
and sex-specific improvements in insulin sensitivity463. sidered adjunctively for those who have struggled with a
One study464 reported that over 3 years vitamin K sup- lifetime of reduced motivation. These potential strategies
plementation was not implicated in the age-related should be key research questions in future work.
changes in skeletal muscle or adipose tissue mass in
older community-dwelling adults. Our understanding Published online xx xx xxxx
1. United Nations, Department of Economic and Social 10. Stewart, S. T., Cutler, D. M. & Rosen, A. B. Forecasting 20. Wilson, M. M. & Morley, J. E. Invited review: aging
Affairs, Population Division. World Population the effects of obesity and smoking on U.S. life and energy balance. J. Appl. Physiol. (1985) 95,
Prospects: The 2017 Revision, Key Findings and expectancy. N. Engl. J. Med. 361, 2252–2260 1728–1736 (2003).
Advance Tables. Working Paper No. ESA/P/WP/248 (2009). 21. Conley, K. E. et al. Ageing, muscle properties and
(United Nations, 2017). 11. Roubenoff, R. Sarcopenic obesity: the confluence of maximal O(2) uptake rate in humans. J. Physiol. 526,
2. Flegal, K. M., Kruszon-Moran, D., Carroll, M. D., two epidemics. Obes. Res. 12, 887–888 (2004). 211–217 (2000).
Fryar, C. D. & Ogden, C. L. Trends in obesity among 12. Patterson, R. E., Frank, L. L., Kristal, A. R. & White, E. 22. Conley, K. E., Jubrias, S. A. & Esselman, P. C.
adults in the United States, 2005 to 2014. JAMA A comprehensive examination of health conditions Oxidative capacity and ageing in human muscle.
315, 2284–2291 (2016). associated with obesity in older adults. Am. J. Prev. J. Physiol. 526, 203–210 (2000).
3. Johnson, N. B., Hayes, L. D., Brown, K., Hoo, E. C. & Med. 27, 385–390 (2004). 23. Cannon, B. & Nedergaard, J. Nonshivering
Ethier, K. A. CDC National Health Report: leading 13. Flegal, K. M. et al. Comparisons of percentage body thermogenesis and its adequate measurement in
causes of morbidity and mortality and associated fat, body mass index, waist circumference, and waist- metabolic studies. J. Exp. Biol. 214, 242–253 (2011).
behavioral risk and protective factors—United States, stature ratio in adults. Am. J. Clin. Nutr. 89, 500–508 24. Dulloo, A. G., Seydoux, J. & Jacquet, J. Adaptive
2005–2013. MMWR Suppl. 63, 3–27 (2014). (2009). thermogenesis and uncoupling proteins: a reappraisal
4. Hales, C. M., Carroll, M. D., Fryar, C. D. & Ogden, C. L. 14. Heo, M., Faith, M. S., Pietrobelli, A. & Heymsfield, S. B. of their roles in fat metabolism and energy balance.
Prevalence of obesity among adults and youth: United Percentage of body fat cutoffs by sex, age, and race- Physiol. Behav. 83, 587–602 (2004).
States, 2015–2016. Centers for Disease Control and ethnicity in the US adult population from NHANES 25. Doucet, E. et al. Appetite after weight loss by energy
Prevention https://www.cdc.gov/nchs/data/databriefs/ 1999–2004. Am. J. Clin. Nutr. 95, 594–602 (2012). restriction and a low-fat diet-exercise follow-up. Int. J.
db288.pdf (2017). 15. Xu, W. et al. Height loss, vertebral fractures, and the Obes. Relat. Metab. Disord. 24, 906–914 (2000).
These are the most updated prevalence rates misclassification of osteoporosis. Bone 48, 307–311 26. Doucet, E. et al. Changes in energy expenditure and
of the obesity epidemic in the United States. (2011). substrate oxidation resulting from weight loss in obese
5. Organisation for Economic Co-operation and 16. Sayer, A. A. et al. The developmental origins of men and women: is there an important contribution of
Development. Obesity Update 2017. OECD sarcopenia. J. Nutr. Health Aging 12, 427–432 (2008). leptin? J. Clin. Endocrinol. Metab. 85, 1550–1556
www.oecd.org/health/obesity-update.htm (2017). This is a review that evaluates the development of (2000).
6. Acciai, F. & Firebaugh, G. Why did life expectancy and life-course influences on muscle mass and 27. Bray, G. A. Effect of caloric restriction on energy
decline in the United States in 2015? A gender- strength. expenditure in obese patients. Lancet 2, 397–398
specific analysis. Soc. Sci. Med. 190, 174–180 17. Abizanda, P. et al. Energetics of aging and frailty: the (1969).
(2017). FRADEA Study. J. Gerontol. A Biol. Sci. Med. Sci. 71, This is an early article that highlights the metabolic
7. Ludwig, D. S. Lifespan weighed down by diet. JAMA 787–796 (2016). changes with energy restriction in patients with
315, 2269–2270 (2016). 18. Weinsier, R. L., Schutz, Y. & Bracco, D. Reexamination obesity.
8. Olshansky, S. J. et al. A potential decline in life of the relationship of resting metabolic rate to fat-free 28. Major, G. C., Doucet, E., Trayhurn, P., Astrup, A. &
expectancy in the United States in the 21st century. mass and to the metabolically active components of Tremblay, A. Clinical significance of adaptive
N. Engl. J. Med. 352, 1138–1145 (2005). fat-free mass in humans. Am. J. Clin. Nutr. 55, thermogenesis. Int. J. Obes. (Lond.) 31, 204–212
9. Preston, S. H., Stokes, A., Mehta, N. K. & Cao, B. 790–794 (1992). (2007).
Projecting the effect of changes in smoking and 19. Gallagher, D. et al. Organ-tissue mass measurement 29. Cohn, S. H. et al. Changes in body chemical
obesity on future life expectancy in the United States. allows modeling of REE and metabolically active tissue composition with age measured by total-body neutron
Demography 51, 27–49 (2014). mass. Am. J. Physiol. 275, E249–E258 (1998). activation. Metabolism 25, 85–95 (1976).

Reviews
30. Tremblay, A., Royer, M. M., Chaput, J. P. & Doucet, E. This is a randomized trial of testosterone therapy limitations in well-functioning older persons.
Adaptive thermogenesis can make a difference in the in symptomatic older men that demonstrates no J. Gerontol. A Biol. Sci. Med. Sci. 60, 324–333 (2005).
ability of obese individuals to lose body weight. benefit in vitality or walking distance following This study shows that in sarcopenic obesity
Int. J. Obes. (Lond.) 37, 759–764 (2013). supplementation. reflected by low cross-sectional thigh muscle area,
31. Astrup, A. et al. Meta-analysis of resting metabolic 54. Orentreich, N., Brind, J. L., Rizer, R. L. & Vogelman, J. H. greater fat infiltration into muscle is associated
rate in formerly obese subjects. Am. J. Clin. Nutr. 69, Age changes and sex differences in serum with mobility loss.
1117–1122 (1999). dehydroepiandrosterone sulfate concentrations 75. Sepe, A., Tchkonia, T., Thomou, T., Zamboni, M. &
32. Rosenbaum, M., Hirsch, J., Gallagher, D. A. & throughout adulthood. J. Clin. Endocrinol. Metab. 59, Kirkland, J. L. Aging and regional differences in fat cell
Leibel, R. L. Long-term persistence of adaptive 551–555 (1984). progenitors — a mini-review. Gerontology 57, 66–75
thermogenesis in subjects who have maintained a 55. Nafziger, A. N., Bowlin, S. J., Jenkins, P. L. & (2011).
reduced body weight. Am. J. Clin. Nutr. 88, 906–912 Pearson, T. A. Longitudinal changes in 76. Kalinkovich, A. & Livshits, G. Sarcopenic obesity or
(2008). dehydroepiandrosterone concentrations in men and obese sarcopenia: a cross talk between age-associated
33. Napier, J. R., Thomas, M. F., Sharma, M., women. J. Lab. Clin. Med. 131, 316–323 (1998). adipose tissue and skeletal muscle inflammation as a
Hodgkinson, S. C. & Bass, J. J. Insulin-like growth 56. Giannoulis, M. G., Martin, F. C., Nair, K. S., main mechanism of the pathogenesis. Ageing Res. Rev.
factor-I protects myoblasts from apoptosis but Umpleby, A. M. & Sonksen, P. Hormone replacement 35, 200–221 (2017).
requires other factors to stimulate proliferation. therapy and physical function in healthy older men. 77. Kob, R. et al. Sarcopenic obesity: molecular clues
J. Endocrinol. 163, 63–68 (1999). Time to talk hormones? Endocr. Rev. 33, 314–377 to a better understanding of its pathogenesis?
34. Roth, S. M. et al. Ultrastructural muscle damage in (2012). Biogerontology 16, 15–29 (2015).
young versus older men after high-volume, heavy- 57. Schrager, M. A. et al. Sarcopenic obesity and 78. Stinkens, R., Goossens, G. H., Jocken, J. W. &
resistance strength training. J. Appl. Physiol. (1985) inflammation in the InCHIANTI study. J. Appl. Physiol. Blaak, E. E. Targeting fatty acid metabolism to improve
86, 1833–1840 (1999). (1985) 102, 919–925 (2007). glucose metabolism. Obes. Rev. 16, 715–757 (2015).
35. Klem, M. L., Wing, R. R., Lang, W., McGuire, M. T. & This is an epidemiological study that shows that 79. Aon, M. A., Bhatt, N. & Cortassa, S. C. Mitochondrial
Hill, J. O. Does weight loss maintenance become obesity directly affects inflammation and negatively and cellular mechanisms for managing lipid excess.
easier over time? Obes. Res. 8, 438–444 (2000). affects muscle strength. Front. Physiol. 5, 282 (2014).
36. Wing, R. R. & Hill, J. O. Successful weight loss 58. Forsythe, L. K., Wallace, J. M. & Livingstone, M. B. 80. Bruce, C. R. et al. Muscle oxidative capacity is a better
maintenance. Annu. Rev. Nutr. 21, 323–341 (2001). Obesity and inflammation: the effects of weight loss. predictor of insulin sensitivity than lipid status. J. Clin.
37. Tremollieres, F. A., Pouilles, J. M. & Ribot, C. A. Nutr. Res. Rev. 21, 117–133 (2008). Endocrinol. Metab. 88, 5444–5451 (2003).
Relative influence of age and menopause on total 59. Park, H. S., Park, J. Y. & Yu, R. Relationship of obesity 81. Kohara, K. Sarcopenic obesity in aging population:
and regional body composition changes in and visceral adiposity with serum concentrations of current status and future directions for research.
postmenopausal women. Am. J. Obstet. Gynecol. CRP, TNF-alpha and IL-6. Diabetes Res. Clin. Pract. Endocrine 45, 15–25 (2014).
175, 1594–1600 (1996). 69, 29–35 (2005). 82. Carnio, S. et al. Autophagy impairment in muscle
38. Sowers, M. et al. Changes in body composition in 60. Zamboni, M., Mazzali, G., Fantin, F., Rossi, A. & induces neuromuscular junction degeneration and
women over six years at midlife: ovarian and Di Francesco, V. Sarcopenic obesity: a new category precocious aging. Cell Rep. 8, 1509–1521 (2014).
chronological aging. J. Clin. Endocrinol. Metab. 92, of obesity in the elderly. Nutr. Metab. Cardiovasc. Dis. 83. Marcell, T. J. Sarcopenia: causes, consequences, and
895–901 (2007). 18, 388–395 (2008). preventions. J. Gerontol. A Biol. Sci. Med. Sci. 58,
39. Milewicz, A., Tworowska, U. & Demissie, M. 61. Hamrick, M. W. Role of the cytokine-like hormone M911–M916 (2003).
Menopausal obesity — myth or fact? Climacteric 4, leptin in muscle-bone crosstalk with aging. J. Bone 84. Wohlgemuth, S. E., Seo, A. Y., Marzetti, E., Lees, H. A.
273–283 (2001). Metab. 24, 1–8 (2017). & Leeuwenburgh, C. Skeletal muscle autophagy and
40. Gambacciani, M. et al. Climacteric modifications in 62. Yeap, B. B. et al. Associations of insulin-like growth apoptosis during aging: effects of calorie restriction
body weight and fat tissue distribution. Climacteric 2, factor-I and its binding proteins and testosterone with and life-long exercise. Exp. Gerontol. 45, 138–148
37–44 (1999). frailty in older men. Clin. Endocrinol. (Oxf.) 78, (2010).
41. Guo, S. S., Zeller, C., Chumlea, W. C. & Siervogel, R. M. 752–759 (2013). 85. Manini, T. M. et al. Reduced physical activity increases
Aging, body composition, and lifestyle: the Fels 63. Wang, Y. et al. Adiponectin inhibits tumor necrosis intermuscular adipose tissue in healthy young adults.
Longitudinal Study. Am. J. Clin. Nutr. 70, 405–411 factor-alpha-induced vascular inflammatory response Am. J. Clin. Nutr. 85, 377–384 (2007).
(1999). via caveolin-mediated ceramidase recruitment and 86. Kusminski, C. M., Shetty, S., Orci, L., Unger, R. H. &
This study presents the natural patterns of change activation. Circ. Res. 114, 792–805 (2014). Scherer, P. E. Diabetes and apoptosis: lipotoxicity.
in body composition in older adults and the 64. Lang, C. H., Frost, R. A., Nairn, A. C., MacLean, D. A. Apoptosis 14, 1484–1495 (2009).
influence of physical activity. & Vary, T. C. TNF-alpha impairs heart and skeletal 87. Nilsson, M. I. et al. Abnormal protein turnover and
42. Enns, D. L. & Tiidus, P. M. Estrogen influences satellite muscle protein synthesis by altering translation anabolic resistance to exercise in sarcopenic obesity.
cell activation and proliferation following downhill initiation. Am. J. Physiol. Endocrinol. Metab. 282, FASEB J. 27, 3905–3916 (2013).
running in rats. J. Appl. Physiol. (1985) 104, E336–E347 (2002). 88. Shefer, G., Rauner, G., Stuelsatz, P., Benayahu, D. &
347–353 (2008). 65. Cartwright, M. J., Tchkonia, T. & Kirkland, J. L. Yablonka-Reuveni, Z. Moderate-intensity treadmill
43. Gambacciani, M. et al. Prospective evaluation of body Aging in adipocytes: potential impact of inherent, running promotes expansion of the satellite cell pool in
weight and body fat distribution in early depot-specific mechanisms. Exp. Gerontol. 42, young and old mice. FEBS J. 280, 4063–4073 (2013).
postmenopausal women with and without hormonal 463–471 (2007). 89. Zwetsloot, K. A., Childs, T. E., Gilpin, L. T. & Booth, F. W.
replacement therapy. Maturitas 39, 125–132 (2001). 66. Shulman, G. I. Ectopic fat in insulin resistance, Non-passaged muscle precursor cells from 32-month
44. Kadi, F. Cellular and molecular mechanisms responsible dyslipidemia, and cardiometabolic disease. N. Engl. old rat skeletal muscle have delayed proliferation and
for the action of testosterone on human skeletal J. Med. 371, 1131–1141 (2014). differentiation. Cell Prolif. 46, 45–57 (2013).
muscle. A basis for illegal performance enhancement. 67. Thomas, D. R. Loss of skeletal muscle mass in aging: 90. Sakuma, K. et al. The adaptive responses in several
Br. J. Pharmacol. 154, 522–528 (2008). examining the relationship of starvation, sarcopenia mediators linked with hypertrophy and atrophy of
45. Bondanelli, M. et al. Activation of the somatotropic and cachexia. Clin. Nutr. 26, 389–399 (2007). skeletal muscle after lower limb unloading in humans.
axis by testosterone in adult men: evidence for a role 68. Nilwik, R. et al. The decline in skeletal muscle mass Acta Physiol. (Oxf.) 197, 151–159 (2009).
of hypothalamic growth hormone-releasing hormone. with aging is mainly attributed to a reduction in type II 91. Srikanthan, P., Hevener, A. L. & Karlamangla, A. S.
Neuroendocrinology 77, 380–387 (2003). muscle fiber size. Exp. Gerontol. 48, 492–498 (2013). Sarcopenia exacerbates obesity-associated insulin
46. Yeap, B. B. Are declining testosterone levels a major 69. Delbono, O. Neural control of aging skeletal muscle. resistance and dysglycemia: findings from the National
risk factor for ill-health in aging men? Int. J. Impot. Res. Aging Cell 2, 21–29 (2003). Health and Nutrition Examination Survey III. PLoS
21, 24–36 (2009). 70. Stenholm, S. et al. Sarcopenic obesity: definition, ONE 5, e10805 (2010).
47. LeBlanc, E. S. et al. Higher testosterone levels are cause and consequences. Curr. Opin. Clin. Nutr. 92. Joseph, A. M., Adhihetty, P. J. & Leeuwenburgh, C.
associated with less loss of lean body mass in older men. Metab. Care 11, 693–700 (2008). Beneficial effects of exercise on age-related
J. Clin. Endocrinol. Metab. 96, 3855–3863 (2011). 71. Bauer, J. et al. Evidence-based recommendations for mitochondrial dysfunction and oxidative stress in
48. Miller, K. K. Androgen deficiency: effects on body optimal dietary protein intake in older people: skeletal muscle. J. Physiol. 594, 5105–5123
composition. Pituitary 12, 116–124 (2009). a position paper from the PROT-AGE Study Group. (2016).
49. Kaplan, S. A., Lee, J. Y., O’Neill, E. A., Meehan, A. G. & J. Am. Med. Dir. Assoc. 14, 542–559 (2013). 93. Schubert, M. M., Sabapathy, S., Leveritt, M. &
Kusek, J. W. Prevalence of low testosterone and its This is a position paper from the PROT-Age study Desbrow, B. Acute exercise and hormones related to
relationship to body mass index in older men with group that recommends an average daily intake of at appetite regulation: a meta-analysis. Sports Med. 44,
lower urinary tract symptoms associated with benign least 1.0–1.2 g protein per kg body weight per day. 387–403 (2014).
prostatic hyperplasia. Aging Male 16, 169–172 72. Gallagher, D. et al. Healthy percentage body fat 94. Roque, F. R. et al. Aerobic exercise reduces oxidative
(2013). ranges: an approach for developing guidelines based stress and improves vascular changes of small
50. Urban, R. J. et al. Testosterone administration to on body mass index. Am. J. Clin. Nutr. 72, 694–701 mesenteric and coronary arteries in hypertension.
elderly men increases skeletal muscle strength and (2000). Br. J. Pharmacol. 168, 686–703 (2013).
protein synthesis. Am. J. Physiol. 269, E820–E826 This study includes ethnically heterogeneous study 95. Kumaraguru, U., Nandakumar, S., Chi, D., Stone, M. &
(1995). populations, which allow the development of Krishnaswamy, G. Resistance training and aerobic
51. Snyder, P. J. et al. Effect of testosterone treatment prediction formulas for healthy percentage body fat. exercise alters immune function (87.25). J. Immunol.
on body composition and muscle strength in men over 73. Goodpaster, B. H. et al. The loss of skeletal muscle 184, 87.25 (2010).
65 years of age. J. Clin. Endocrinol. Metab. 84, strength, mass, and quality in older adults: the health, 96. Carraro, F., Stuart, C. A., Hartl, W. H., Rosenblatt, J. &
2647–2653 (1999). aging and body composition study. J. Gerontol. A Biol. Wolfe, R. R. Effect of exercise and recovery on muscle
52. Ferrando, A. A. et al. Testosterone administration to Sci. Med. Sci. 61, 1059–1064 (2006). protein synthesis in human subjects. Am. J. Physiol.
older men improves muscle function: molecular and This study shows that loss of strength with ageing is 259, E470–E476 (1990).
physiological mechanisms. Am. J. Physiol. Endocrinol. much more rapid than the concomitant loss of 97. Drummond, M. J. et al. Rapamycin administration in
Metab. 282, E601–E607 (2002). muscle mass, suggesting a decline in muscle quality. humans blocks the contraction-induced increase in
53. Snyder, P. J. et al. Effects of testosterone treatment in 74. Visser, M. et al. Muscle mass, muscle strength, and skeletal muscle protein synthesis. J. Physiol. 587,
older men. N. Engl. J. Med. 374, 611–624 (2016). muscle fat infiltration as predictors of incident mobility 1535–1546 (2009).
Reviews
98. Fujita, S. et al. Aerobic exercise overcomes the 118. Woods, J. A., Wilund, K. R., Martin, S. A. & Kistler, B. M. mechanical properties of older individuals. J. Physiol.
age-related insulin resistance of muscle protein Exercise, inflammation and aging. Aging Dis. 3, 548, 971–981 (2003).
metabolism by improving endothelial function and 130–140 (2012). 141. Kamen, G. & Knight, C. A. Training-related adaptations
Akt/mammalian target of rapamycin signaling. 119. Visser, M. et al. Relationship of interleukin-6 and tumor in motor unit discharge rate in young and older adults.
Diabetes 56, 1615–1622 (2007). necrosis factor-alpha with muscle mass and muscle J. Gerontol. A Biol. Sci. Med. Sci. 59, 1334–1338
99. Levenhagen, D. K. et al. Postexercise nutrient intake strength in elderly men and women: the Health (2004).
timing in humans is critical to recovery of leg glucose ABC Study. J. Gerontol. A Biol. Sci. Med. Sci. 57, 142. Prestes, J. et al. Effects of resistance training on
and protein homeostasis. Am. J. Physiol. Endocrinol. M326–M332 (2002). resistin, leptin, cytokines, and muscle force in
Metab. 280, E982–E993 (2001). 120. Cappola, A. R. et al. Insulin-like growth factor I and elderly post-menopausal women. J. Sports Sci. 27,
100. Sheffield-Moore, M. et al. Postexercise protein interleukin-6 contribute synergistically to disability 1607–1615 (2009).
metabolism in older and younger men following and mortality in older women. J. Clin. Endocrinol. 143. Nindl, B. C. et al. Leptin concentrations experience a
moderate-intensity aerobic exercise. Am. J. Physiol. Metab. 88, 2019–2025 (2003). delayed reduction after resistance exercise in men.
Endocrinol. Metab. 287, E513–E522 (2004). 121. Suetta, C. et al. Training-induced changes in muscle Med. Sci. Sports Exerc. 34, 608–613 (2002).
101. Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N. CSA, muscle strength, EMG, and rate of force 144. Bouassida, A. et al. Leptin, its implication in physical
& Nair, K. S. Age and aerobic exercise training effects development in elderly subjects after long-term exercise and training: a short review. J. Sports Sci. Med.
on whole body and muscle protein metabolism. Am. J. unilateral disuse. J. Appl. Physiol. (1985) 97, 5, 172–181 (2006).
Physiol. Endocrinol. Metab. 286, E92–E101 (2004). 1954–1961 (2004). 145. Fatouros, I. G. et al. Leptin and adiponectin responses
102. Yarasheski, K. E., Zachwieja, J. J. & Bier, D. M. Acute 122. Marzetti, E. et al. Modulation of age-induced in overweight inactive elderly following resistance
effects of resistance exercise on muscle protein apoptotic signaling and cellular remodeling by training and detraining are intensity related. J. Clin.
synthesis rate in young and elderly men and women. exercise and calorie restriction in skeletal muscle. Endocrinol. Metab. 90, 5970–5977 (2005).
Am. J. Physiol. 265, E210–E214 (1993). Free Radic. Biol. Med. 44, 160–168 (2008). 146. Rostas, I. et al. In middle-aged and old obese patients,
103. Yarasheski, K. E. et al. Resistance exercise training 123. Canto, C. et al. AMPK regulates energy expenditure training intervention reduces leptin level: a meta-
increases mixed muscle protein synthesis rate in frail by modulating NAD+ metabolism and SIRT1 activity. analysis. PLoS ONE 12, e0182801 (2017).
women and men >/=76 yr old. Am. J. Physiol. 277, Nature 458, 1056–1060 (2009). 147. Nikseresht, M., Sadeghifard, N., Agha-Alinejad, H. &
E118–E125 (1999). 124. Marzetti, E. et al. Physical activity and exercise as Ebrahim, K. Inflammatory markers and adipocytokine
104. Hasten, D. L., Pak-Loduca, J., Obert, K. A. & countermeasures to physical frailty and sarcopenia. responses to exercise training and detraining in men
Yarasheski, K. E. Resistance exercise acutely increases Aging Clin. Exp. Res. 29, 35–42 (2017). who are obese. J. Strength Cond. Res. 28,
MHC and mixed muscle protein synthesis rates in This study provides an overview of the interplay 3399–3410 (2014).
78–84 and 23–32 yr olds. Am. J. Physiol. Endocrinol. between physical activity, exercise and sarcopenia. 148. Friedenreich, C. M. et al. Changes in insulin resistance
Metab. 278, E620–E626 (2000). 125. Hood, D. A. Mechanisms of exercise-induced indicators, IGFs, and adipokines in a year-long trial of
105. Villareal, D. T., Smith, G. I., Sinacore, D. R., Shah, K. & mitochondrial biogenesis in skeletal muscle. Appl. aerobic exercise in postmenopausal women. Endocr.
Mittendorfer, B. Regular multicomponent exercise Physiol. Nutr. Metab. 34, 465–472 (2009). Relat. Cancer 18, 357–369 (2011).
increases physical fitness and muscle protein 126. Mooren, F. C. & Kruger, K. Exercise, autophagy, and 149. Haider, S. et al. Change in inflammatory parameters in
anabolism in frail, obese, older adults. Obesity apoptosis. Prog. Mol. Biol. Transl Sci. 135, 407–422 prefrail and frail persons obtaining physical training
(Silver Spring) 19, 312–318 (2011). (2015). and nutritional support provided by lay volunteers:
This study demonstrates that a multicomponent 127. Wohlgemuth, S. E. et al. An exploratory analysis of the a randomized controlled trial. PLoS ONE 12,
exercise programme consisting of strength, effects of a weight loss plus exercise program on e0185879 (2017).
endurance, flexibility and balance increases the cellular quality control mechanisms in older overweight 150. Woodrow, G. Body composition analysis techniques in
basal rate of muscle protein synthesis without women. Rejuvenation Res. 14, 315–324 (2011). the aged adult: indications and limitations. Curr. Opin.
affecting the magnitude of the muscle protein 128. Lambert, C. P. & Evans, W. J. Adaptations to aerobic Clin. Nutr. Metab. Care 12, 8–14 (2009).
anabolic response to feeding. and resistance exercise in the elderly. Rev. Endocr. 151. Heymsfield, S. B., Gonzalez, M. C., Lu, J., Jia, G. &
106. Cuthbertson, D. et al. Anabolic signaling deficits Metab. Disord. 6, 137–143 (2005). Zheng, J. Skeletal muscle mass and quality: evolution
underlie amino acid resistance of wasting, aging 129. Moayedi, Y. et al. The prognostic significance of frailty of modern measurement concepts in the context of
muscle. FASEB J. 19, 422–424 (2005). compared to peak oxygen consumption and B-type sarcopenia. Proc. Nutr. Soc. 74, 355–366 (2015).
107. Volpi, E., Mittendorfer, B., Rasmussen, B. B. & natriuretic peptide in patients with advanced heart This is a crucial review that elicits important
Wolfe, R. R. The response of muscle protein failure. Clin. Transplant. https://doi.org/10.1111/ questions related to loss of lean tissues with
anabolism to combined hyperaminoacidemia and ctr.13158 (2018). dieting.
glucose-induced hyperinsulinemia is impaired in the 130. Jones, S. et al. Assessment of exercise capacity and 152. Baracos, V. et al. Advances in the science and
elderly. J. Clin. Endocrinol. Metab. 85, 4481–4490 oxygen consumption using a 6 min stepper test in application of body composition measurement.
(2000). older adults. Front. Physiol. 8, 408 (2017). JPEN J. Parenter. Enteral Nutr. 36, 96–107 (2012).
This study highlights the anabolic response to 131. Binder, E. F. et al. Effects of exercise training on frailty 153. Earthman, C. P. Body composition tools for
feeding in elderly individuals that underscores in community-dwelling older adults: results of a assessment of adult malnutrition at the bedside:
sarcopenia of ageing. randomized, controlled trial. J. Am. Geriatr. Soc. 50, a tutorial on research considerations and clinical
108. Volpi, E., Sheffield-Moore, M., Rasmussen, B. B. & 1921–1928 (2002). applications. JPEN J. Parenter. Enteral Nutr. 39,
Wolfe, R. R. Basal muscle amino acid kinetics and This is a randomized controlled trial demonstrating 787–822 (2015).
protein synthesis in healthy young and older men. that intensive exercise training can improve 154. Heymsfield, S. B., Gonzalez, M. C., Shen, W.,
JAMA 286, 1206–1212 (2001). measures of physical function. Redman, L. & Thomas, D. Weight loss composition is
109. Peterson, C. M., Johannsen, D. L. & Ravussin, E. 132. Villareal, D. T., Banks, M., Siener, C., Sinacore, D. R. & one-fourth fat-free mass: a critical review and critique of
Skeletal muscle mitochondria and aging: a review. Klein, S. Physical frailty and body composition in this widely cited rule. Obes. Rev. 15, 310–321 (2014).
J. Aging Res. 2012, 194821 (2012). obese elderly men and women. Obes. Res. 12, 155. Teigen, L. M., Kuchnia, A. J., Mourtzakis, M. &
110. Dreyer, H. C., Blanco, C. E., Sattler, F. R., Schroeder, E. T. 913–920 (2004). Earthman, C. P. The use of technology for estimating
& Wiswell, R. A. Satellite cell numbers in young and 133. Lambert, C. P., Wright, N. R., Finck, B. N. & body composition strengths and weaknesses of
older men 24 hours after eccentric exercise. Muscle Villareal, D. T. Exercise but not diet-induced weight common modalities in a clinical setting [formula:
Nerve 33, 242–253 (2006). loss decreases skeletal muscle inflammatory gene see text]. Nutr. Clin. Pract. 32, 20–29 (2017).
111. Petrella, J. K., Kim, J. S., Mayhew, D. L., Cross, J. M. & expression in frail obese elderly persons. J. Appl. 156. Cruz-Jentoft, A. J. et al. Sarcopenia: European
Bamman, M. M. Potent myofiber hypertrophy during Physiol. (1985) 105, 473–478 (2008). consensus on definition and diagnosis: Report of the
resistance training in humans is associated with satellite 134. Greiwe, J. S., Cheng, B., Rubin, D. C., Yarasheski, K. E. European Working Group on Sarcopenia in Older
cell-mediated myonuclear addition: a cluster analysis. & Semenkovich, C. F. Resistance exercise decreases People. Age Ageing 39, 412–423 (2010).
J. Appl. Physiol. (1985) 104, 1736–1742 (2008). skeletal muscle tumor necrosis factor alpha in frail 157. Kendler, D. L. et al. The Official Positions of the
112. Kang, J. S. & Krauss, R. S. Muscle stem cells in elderly humans. FASEB J. 15, 475–482 (2001). International Society for Clinical Densitometry:
developmental and regenerative myogenesis. Curr. 135. Gielen, S. et al. Anti-inflammatory effects of exercise indications of use and reporting of DXA for body
Opin. Clin. Nutr. Metab. Care 13, 243–248 (2010). training in the skeletal muscle of patients with chronic composition. J. Clin. Densitom. 16, 496–507 (2013).
113. Thornell, L. E. Sarcopenic obesity: satellite cells in the heart failure. J. Am. Coll. Cardiol. 42, 861–868 (2003). 158. Fakhrawi, D. H. et al. Comparison of body composition
aging muscle. Curr. Opin. Clin. Nutr. Metab. Care 14, 136. Markofski, M. M. et al. Exercise training modifies by bioelectrical impedance and dual-energy x-ray
22–27 (2011). ghrelin and adiponectin concentrations and is related absorptiometry in overweight/obese postmenopausal
114. Bruunsgaard, H., Bjerregaard, E., Schroll, M. & to inflammation in older adults. J. Gerontol. A Biol. women. J. Clin. Densitom. 12, 238–244 (2009).
Pedersen, B. K. Muscle strength after resistance Sci. Med. Sci. 69, 675–681 (2014). 159. Bridge, P. et al. Validation of longitudinal DXA changes
training is inversely correlated with baseline levels of 137. Andersen, L. L. et al. Changes in the human muscle in body composition from pre- to mid-adolescence
soluble tumor necrosis factor receptors in the oldest force-velocity relationship in response to resistance using MRI as reference. J. Clin. Densitom. 14,
old. J. Am. Geriatr. Soc. 52, 237–241 (2004). training and subsequent detraining. J. Appl. Physiol. 340–347 (2011).
115. Kohut, M. L. et al. Aerobic exercise, but not flexibility/ (1985) 99, 87–94 (2005). 160. Xu, L. et al. Comparisons of body-composition
resistance exercise, reduces serum IL-18, CRP, and 138. Englund, D. A., Sharp, R. L., Selsby, J. T., Ganesan, S. S. prediction accuracy: a study of 2 bioelectric impedance
IL-6 independent of beta-blockers, BMI, and & Franke, W. D. Resistance training performed at consumer devices in healthy chinese persons using
psychosocial factors in older adults. Brain Behav. distinct angular velocities elicits velocity-specific DXA and MRI as criteria methods. J. Clin. Densitom.
Immun. 20, 201–209 (2006). alterations in muscle strength and mobility status in 14, 458–464 (2011).
116. Forti, L. N. et al. Strength training reduces circulating older adults. Exp. Gerontol. 91, 51–56 (2017). 161. Park, Y. W., Heymsfield, S. B. & Gallagher, D. Are
interleukin-6 but not brain-derived neurotrophic factor 139. Fatouros, I. G. et al. Intensity of resistance exercise dual-energy X-ray absorptiometry regional estimates
in community-dwelling elderly individuals. Age (Dordr.) determines adipokine and resting energy expenditure associated with visceral adipose tissue mass? Int. J.
36, 9704 (2014). responses in overweight elderly individuals. Diabetes Obes. Relat. Metab. Disord. 26, 978–983 (2002).
117. Beyer, I., Mets, T. & Bautmans, I. Chronic low-grade Care 32, 2161–2167 (2009). 162. Kaul, S. et al. Dual-energy X-ray absorptiometry for
inflammation and age-related sarcopenia. Curr. Opin. 140. Reeves, N. D., Maganaris, C. N. & Narici, M. V. Effect quantification of visceral fat. Obesity 20, 1313–1318
Clin. Nutr. Metab. Care 15, 12–22 (2012). of strength training on human patella tendon (2012).

Reviews
163. Micklesfield, L. K., Goedecke, J. H., Punyanitya, M., presents evidence and a definition for the and without obesity, and mortality: results from
Wilson, K. E. & Kelly, T. L. Dual-energy X-ray performs identification of sarcopenia. the 1999–2004 National Health and Nutrition
as well as clinical computed tomography for the 181. Janssen, I., Baumgartner, R. N., Ross, R., Examination Survey. J. Gerontol. A Biol. Sci. Med. Sci.
measurement of visceral fat. Obesity 20, 1109–1114 Rosenberg, I. H. & Roubenoff, R. Skeletal muscle 72, 1445–1451 (2017).
(2012). cutpoints associated with elevated physical disability This report details the definition of low lean mass
164. Das, S. K. et al. Body composition assessment in risk in older men and women. Am. J. Epidemiol. 159, determined by the Foundation of the National
extreme obesity and after massive weight loss induced 413–421 (2004). Institutes of Health, as well as the adverse
by gastric bypass surgery. Am. J. Physiol. Endocrinol. 182. Studenski, S. A. et al. The FNIH sarcopenia project: association between low lean mass and mortality.
Metab. 284, E1080–E1088 (2003). rationale, study description, conference 199. Kim, T. N. et al. Prevalence of sarcopenia and
165. Schautz, B., Later, W., Heller, M., Muller, M. J. & recommendations, and final estimates. J. Gerontol. A sarcopenic obesity in Korean adults: the Korean
Bosy-Westphal, A. Total and regional relationship Biol. Sci. Med. Sci. 69, 547–558 (2014). sarcopenic obesity study. Int. J. Obes. (Lond.) 33,
between lean and fat mass with increasing This report details recommendations from the 885–892 (2009).
adiposity — impact for the diagnosis of sarcopenic Foundation of the National Institutes on Health 200. Stenholm, S. et al. The effect of obesity combined
obesity. Eur. J. Clin. Nutr. 66, 1356–1361 (2012). Sarcopenia Project, which aggregated multiple with low muscle strength on decline in mobility in
166. Bosy-Westphal, A. & Muller, M. J. Identification of cohorts of older adults and created cut-off points older persons: results from the InCHIANTI study.
skeletal muscle mass depletion across age and BMI to permit identification of low muscle mass and low Int. J. Obes. (Lond.) 33, 635–644 (2009).
groups in health and disease—there is need for a unified muscle strength. This study details data from the InCHIANTI study
definition. Int. J. Obes. (Lond.) 39, 379–386 (2015). 183. Kemmler, W. et al. Prevalence of sarcopenia and that prove that obesity combined with low muscle
This review argues for the importance of sarcopenic obesity in older German men using strength increases the risk of mobility disability
standardized definitions in skeletal muscle mass. recognized definitions: high accordance but low with age.
167. Bosy-Westphal, A. et al. Quantification of whole-body overlap! Osteoporos. Int. 28, 1881–1891 (2017). 201. Stephen, W. C. & Janssen, I. Sarcopenic-obesity and
and segmental skeletal muscle mass using phase- 184. Cruz-Jentoft, A. J. et al. Prevalence of and cardiovascular disease risk in the elderly. J. Nutr.
sensitive 8-electrode medical bioelectrical impedance interventions for sarcopenia in ageing adults: Health Aging 13, 460–466 (2009).
devices. Eur. J. Clin. Nutr. 71, 1061–1067 (2017). a systematic review. Report of the International 202. Alley, D. E. et al. Grip strength cutpoints for the
168. Houtkooper, L. B., Lohman, T. G., Going, S. B. & Sarcopenia Initiative (EWGSOP and IWGS). identification of clinically relevant weakness. J. Gerontol.
Howell, W. H. Why bioelectrical impedance analysis Age Ageing 43, 748–759 (2014). A Biol. Sci. Med. Sci. 69, 559–566 (2014).
should be used for estimating adiposity. Am. J. Clin. 185. Chen, L. K. et al. Sarcopenia in Asia: consensus report 203. Rolland, Y. et al. Difficulties with physical function
Nutr. 64, 436S–448S (1996). of the Asian Working Group for Sarcopenia. J. Am. associated with obesity, sarcopenia, and sarcopenic-
169. Kyle, U. G. et al. Bioelectrical impedance analysis-part II: Med. Dir. Assoc. 15, 95–101 (2014). obesity in community-dwelling elderly women: the
utilization in clinical practice. Clin. Nutr. 23, 1430–1453 186. Villareal, D. T. et al. Obesity in older adults: technical EPIDOS (EPIDemiologie de l’OSteoporose) Study.
(2004). review and position statement of the American Society Am. J. Clin. Nutr. 89, 1895–1900 (2009).
This study demonstrates the application of for Nutrition and NAASO, The Obesity Society. Am. J. 204. Hirani, V. et al. Longitudinal associations between
bioelectrical impedance equations in clinical Clin. Nutr. 82, 923–934 (2005). body composition, sarcopenic obesity and outcomes
practice, as advocated by ESPEN. This study highlights current guidelines for the of frailty, disability, institutionalisation and mortality in
170. Chumlea, W. C. et al. Body composition estimates management of older adults with obesity. community-dwelling older men: The Concord Health
from NHANES III bioelectrical impedance data. Int. J. 187. Garvey, W. T. et al. American Association of Clinical and Ageing in Men Project. Age Ageing 46, 413–420
Obes. Relat. Metab. Disord. 26, 1596–1609 (2002). Endocrinologists and American College of (2017).
This study presents normative bioelectrical Endocrinology comprehensive clinical practice 205. Zoico, E. et al. Physical disability and muscular
impedance analysis equations validated using a guidelines for medical care of patients with obesity. strength in relation to obesity and different body
population-based cohort of American adults. Endocr. Pract. 22 (Suppl. 3), 1–203 (2016). composition indexes in a sample of healthy elderly
171. Janssen, I., Heymsfield, S. B., Baumgartner, R. N. & Guidelines for the management of obesity by the women. Int. J. Obes. Relat. Metab. Disord. 28,
Ross, R. Estimation of skeletal muscle mass by AACE/ACE. 234–241 (2004).
bioelectrical impedance analysis. J. Appl. Physiol. 188. Bouchard, D. R., Dionne, I. J. & Brochu, M. Sarcopenic/ 206. Schaap, L. A., Koster, A. & Visser, M. Adiposity, muscle
(1985) 89, 465–471 (2000). obesity and physical capacity in older men and women: mass, and muscle strength in relation to functional
172. Mally, K., Trentmann, J., Heller, M. & Dittmar, M. data from the Nutrition as a Determinant of Successful decline in older persons. Epidemiol. Rev. 35, 51–65
Reliability and accuracy of segmental bioelectrical Aging (NuAge)-the Quebec longitudinal Study. Obesity (2013).
impedance analysis for assessing muscle and fat mass (Silver Spring) 17, 2082–2088 (2009). This is a meta-analysis that proves the longitudinal
in older Europeans: a comparison with dual-energy 189. Durstine, J. in ACSM’s Exercise Management for impact of BMI on incident loss of muscle mass and
X-ray absorptiometry. Eur. J. Appl. Physiol. (1985) Persons with Chronic Diseases and Disabilities 4th muscle strength.
111, 1879–1887 (2011). edn (eds Moore, G. E., Durstine, J. L. & Painter, P. L.) 207. Batsis, J. A., Zbehlik, A. J., Pidgeon, D. & Bartels, S. J.
173. Yu, S. C., Powell, A., Khow, K. S. & Visvanathan, R. The (Human Kinetics, 2016). Dynapenic obesity and the effect on long-term
performance of five bioelectrical impedance analysis 190. Baumgartner, R. N. et al. Epidemiology of sarcopenia physical function and quality of life: data from the
prediction equations against dual x-ray among the elderly in New Mexico. Am. J. Epidemiol. osteoarthritis initiative. BMC Geriatr. 15, 118 (2015).
absorptiometry in estimating appendicular skeletal 147, 755–763 (1998). 208. Sayers, S. P. et al. Validation of the late-life function
muscle mass in an adult Australian population. This is a landmark study that demonstrates the and disability instrument. J. Am. Geriatr. Soc. 52,
Nutrients 8, 189 (2016). prevalence of sarcopenia in a cohort of older adults 1554–1559 (2004).
174. Chien, M. Y., Huang, T. Y. & Wu, Y. T. Prevalence of in the New Mexico Elder Health Survey. 209. Ware, J. Jr, Kosinski, M. & Keller, S. D. A. 12-item
sarcopenia estimated using a bioelectrical impedance 191. Baumgartner, R. N. et al. Sarcopenic obesity predicts short-form health survey: construction of scales and
analysis prediction equation in community-dwelling instrumental activities of daily living disability in the preliminary tests of reliability and validity. Med. Care
elderly people in Taiwan. J. Am. Geriatr. Soc. 56, elderly. Obes. Res. 12, 1995–2004 (2004). 34, 220–233 (1996).
1710–1715 (2008). This study highlights the synergistic problems of 210. Yang, M., Jiang, J., Hao, Q., Luo, L. & Dong, B.
175. Roubenoff, R. Applications of bioelectrical impedance sarcopenia and obesity that lead to impairments in Dynapenic obesity and lower extremity function in
analysis for body composition to epidemiologic instrumental activities of daily living. elderly adults. J. Am. Med. Dir. Assoc. 16, 31–36
studies. Am J. Clin. Nutr. 64, 459S–462S (1996). 192. Fox, C. S. et al. Abdominal visceral and subcutaneous (2015).
176. Kyle, U. G. et al. Bioelectrical impedance analysis — adipose tissue compartments: association with 211. Kim, Y. et al. Adiposity and grip strength as long-term
part I: review of principles and methods. Clin. Nutr. metabolic risk factors in the Framingham Heart Study. predictors of objectively measured physical activity in
23, 1226–1243 (2004). Circulation 116, 39–48 (2007). 93 015 adults: the UK Biobank study. Int. J. Obes.
177. Batsis, J. A., Mackenzie, T. A., Lopez-Jimenez, F. & 193. Despres, J. P. Body fat distribution and risk of (Lond.) 41, 1361–1368 (2017).
Bartels, S. J. Sarcopenia, sarcopenic obesity, and cardiovascular disease: an update. Circulation 126, This study analyses data from the UK Biobank
functional impairments in older adults: National 1301–1313 (2012). study and shows that advanced obesity and poor
Health and Nutrition Examination Surveys 194. Batsis, J. A. et al. Diagnostic accuracy of body mass strength at baseline independently predict lower
1999–2004. Nutr. Res. 35, 1031–1039 (2015). index to identify obesity in older adults: NHANES activities at follow-up.
178. Batsis, J. A. et al. Variation in the prevalence of 1999–2004. Int. J. Obes. (Lond.) 40, 761–767 (2016). 212. Jung, S. et al. Obesity and muscle weakness as risk
sarcopenia and sarcopenic obesity in older adults This study emphasizes the challenges of using BMI factors for mobility limitation in community-dwelling
associated with different research definitions: as a marker for obesity. BMI has a poor sensitivity older Japanese women: a two-year follow-up
dual-energy X-ray absorptiometry data from the in ascertaining body fat-defined obesity that investigation. J. Nutr. Health Aging 20, 28–34 (2016).
National Health and Nutrition Examination Survey worsens with age. 213. Ochi, M. et al. Quadriceps sarcopenia and visceral
1999–2004. J. Am. Geriatr. Soc. 61, 974–980 195. Schrauwen-Hinderling, V. B., Hesselink, M. K., obesity are risk factors for postural instability in the
(2013). Schrauwen, P. & Kooi, M. E. Intramyocellular lipid middle-aged to elderly population. Geriatr. Gerontol.
This study applies multiple definitions of sarcopenic content in human skeletal muscle. Obesity (Silver Int. 10, 233–243 (2010).
obesity on a cohort of American adults and Spring) 14, 357–367 (2006). 214. Baek, S. J. et al. Sarcopenia and sarcopenic obesity
emphasizes the varied prevalences of this disorder. 196. Kemmler, W., von Stengel, S., Engelke, K., Sieber, C. & and their association with dyslipidemia in Korean
179. Dehghan, M. & Merchant, A. T. Is bioelectrical Freiberger, E. Prevalence of sarcopenic obesity in elderly men: the 2008–2010 Korea National Health
impedance accurate for use in large epidemiological Germany using established definitions: baseline and Nutrition Examination Survey. J. Endocrinol.
studies? Nutr. J. 7, 26 (2008). data of the FORMOsA study. Osteoporos. Int. 27, Invest. 37, 247–260 (2014).
180. Fielding, R. A. et al. Sarcopenia: an undiagnosed 275–281 (2016). 215. Chung, J. Y., Kang, H. T., Lee, D. C., Lee, H. R. & Lee, Y. J.
condition in older adults. Current consensus definition: 197. Johnson Stoklossa, C. A. et al. Prevalence of Body composition and its association with
prevalence, etiology, and consequences. International sarcopenic obesity in adults with class II/III obesity cardiometabolic risk factors in the elderly: a focus
working group on sarcopenia. J. Am. Med. Dir. Assoc. using different diagnostic criteria. J. Nutr. Metab. on sarcopenic obesity. Arch. Gerontol. Geriatr. 56,
12, 249–256 (2011). 2017, 7307618 (2017). 270–278 (2013).
This is a consensus statement from the 198. Batsis, J. A., Mackenzie, T. A., Emeny, R. T., 216. Batsis, J. A., Mackenzie, T. A., Jones, J. D.,
International Working Group on Sarcopenia that Lopez-Jimenez, F. & Bartels, S. J. Low lean mass with Lopez-Jimenez, F. & Bartels, S. J. Sarcopenia,
Reviews
sarcopenic obesity and inflammation: results from the sarcopenic obesity and better perceived health among 257. Schoenfeld, B. J., Aragon, A. A. & Krieger, J. W.
1999–2004 National Health and Nutrition Examination the elderly: the EXERNET multi-center study. J. Nutr. The effect of protein timing on muscle strength and
Survey. Clin. Nutr. 35, 1472–1483 (2016). Health Aging 19, 211–217 (2015). hypertrophy: a meta-analysis. J. Int. Soc. Sports Nutr.
217. Aubertin-Leheudre, M., Lord, C., Goulet, E. D., Khalil, A. 238. Cawthon, P. M. et al. Sarcopenia and health care 10, 53 (2013).
& Dionne, I. J. Effect of sarcopenia on cardiovascular utilization in older women. J. Gerontol. A Biol. Sci. 258. Smith, G. I. et al. High-protein intake during weight loss
disease risk factors in obese postmenopausal women. Med. Sci. 72, 95–101 (2017). therapy eliminates the weight-loss-induced
Obesity (Silver Spring) 14, 2277–2283 (2006). 239. Akune, T. et al. Incidence of certified need of care in improvement in insulin action in obese postmenopausal
218. Lee, S., Kim, T. N. & Kim, S. H. Sarcopenic obesity is the long-term care insurance system and its risk women. Cell Rep. 17, 849–861 (2016).
more closely associated with knee osteoarthritis than factors in the elderly of Japanese population-based 259. Deutz, N. E. et al. Protein intake and exercise for
is nonsarcopenic obesity: a cross-sectional study. cohorts: the ROAD study. Geriatr. Gerontol. Int. 14, optimal muscle function with aging: recommendations
Arthritis Rheum. 64, 3947–3954 (2012). 695–701 (2014). from the ESPEN Expert Group. Clin. Nutr. 33, 929–936
219. Scott, D. et al. Sarcopenic obesity and dynapenic 240. Zizza, C. A., Herring, A., Stevens, J. & Popkin, B. M. (2014).
obesity: 5-year associations with falls risk in middle- Obesity affects nursing-care facility admission among These are the European Society for Clinical
aged and older adults. Obesity (Silver Spring) 22, whites but not blacks. Obes. Res. 10, 816–823 (2002). Nutrition and Metabolism workshop
1568–1574 (2014). 241. Elkins, J. S. et al. Midlife obesity and long-term risk of recommendations on protein requirements in
220. Scott, D. et al. Associations of sarcopenic obesity and nursing home admission. Obesity (Silver Spring) 14, elderly individuals.
dynapenic obesity with bone mineral density and 1472–1478 (2006). 260. Bouillanne, O. et al. Impact of protein pulse feeding on
incident fractures over 5–10 years in community- 242. Valiyeva, E., Russell, L. B., Miller, J. E. & Safford, M. M. lean mass in malnourished and at-risk hospitalized
dwelling older adults. Calcif. Tissue Int. 99, 30–42 Lifestyle-related risk factors and risk of future nursing elderly patients: a randomized controlled trial.
(2016). home admission. Arch. Intern. Med. 166, 985–990 Clin. Nutr. 32, 186–192 (2013).
221. Atkins, J. L. et al. Sarcopenic obesity and risk of (2006). 261. Beasley, J. M. et al. Protein intake and incident frailty
cardiovascular disease and mortality: a population- 243. Kritchevsky, S. B. et al. Intentional weight loss and all- in the Women’s Health Initiative observational study.
based cohort study of older men. J. Am. Geriatr. Soc. cause mortality: a meta-analysis of randomized clinical J. Am. Geriatr. Soc. 58, 1063–1071 (2010).
62, 253–260 (2014). trials. PLoS ONE 10, e0121993 (2015). 262. Tieland, M. et al. Protein supplementation improves
222. Hamer, M., Batty, G. D. & Kivimaki, M. Sarcopenic This is an important meta-analysis that evaluates physical performance in frail elderly people:
obesity and risk of new onset depressive symptoms in randomized controlled trials of weight loss a randomized, double-blind, placebo-controlled trial.
older adults: English Longitudinal Study of Ageing. interventions in older adults and their impact on J. Am. Med. Dir. Assoc. 13, 720–726 (2012).
Int. J. Obes. (Lond.) 39, 1717–1720 (2015). mortality. 263. Porter Starr, K. N. et al. Improved function with
This study includes longitudinal data that suggest 244. Batsis, J. A., Huyck, K. L. & Bartels, S. J. Challenges enhanced protein intake per meal: a pilot study of
an association between sarcopenic obesity and with the Medicare obesity benefit: practical concerns weight reduction in frail, obese older adults. J. Gerontol.
depression. & proposed solutions. J. Gen. Intern. Med. 30, A Biol. Sci. Med. Sci. 71, 1369–1375 (2016).
223. Ishii, S. et al. The association between sarcopenic 118–122 (2015). 264. Verreijen, A. M. et al. Effect of a high protein diet and/
obesity and depressive symptoms in older Japanese 245. Jensen, M. D. et al. 2013 AHA/ACC/TOS guideline for or resistance exercise on the preservation of fat free
adults. PLoS ONE 11, e0162898 (2016). the management of overweight and obesity in adults. mass during weight loss in overweight and obese older
224. Mei, K. L., Batsis, J. A., Mills, J. B. & Holubar, S. D. Circulation 129, S102–S138 (2014). adults: a randomized controlled trial. Nutr. J. 16, 10
Sarcopenia and sarcopenic obesity: do they predict This report provides clinical obesity guidelines (2017).
inferior oncologic outcomes after gastrointestinal endorsed by multiple national societies. 265. Sammarco, R. et al. Evaluation of hypocaloric diet with
cancer surgery? Perioper. Med. (Lond.) 5, 30 (2016). 246. Villareal, D. T. et al. Weight loss, exercise, or both and protein supplementation in middle-aged sarcopenic
225. Androga, L., Sharma, D., Amodu, A. & Abramowitz, M. K. physical function in obese older adults. N. Engl. J. obese women: a pilot study. Obes. Facts 10, 160–167
Sarcopenia, obesity, and mortality in US adults with and Med. 364, 1218–1229 (2011). (2017).
without chronic kidney disease. Kidney Int. Rep. 2, This is a randomized trial of older adults with 266. Avenell, A. & Handoll, H. H. Nutritional supplementation
201–211 (2017). frailty and obesity that compares diet, exercise for hip fracture aftercare in older people. Cochrane
226. Malhotra, R. et al. Sarcopenic obesity definitions by type and controls and demonstrates that physical Database Syst. Rev. 1, CD001880 (2010).
body composition and mortality in the hemodialysis function improves and muscle and bone loss is 267. Cawood, A. L., Elia, M. & Stratton, R. J. Systematic
patients. J. Ren. Nutr. 27, 84–90 (2017). mitigated with concomitant exercise therapy. review and meta-analysis of the effects of high protein
227. Rossi, A. P. et al. Dynapenic abdominal obesity as a 247. Villareal, D. T. et al. Aerobic or resistance exercise, oral nutritional supplements. Ageing Res. Rev. 11,
predictor of worsening disability, hospitalization, or both in dieting obese older adults. N. Engl. J. Med. 278–296 (2012).
and mortality in older adults: results from the 376, 1943–1955 (2017). 268. Milne, A. C., Potter, J., Vivanti, A. & Avenell, A. Protein
InCHIANTI Study. J. Gerontol. A Biol. Sci. Med. Sci. This is a randomized trial of older adults with and energy supplementation in elderly people at risk
72, 1098–1104 (2017). obesity and frailty demonstrating that weight loss from malnutrition. Cochrane Database Syst. Rev. 2,
228. Stenholm, S. et al. Obesity and muscle strength as coupled with both aerobic and resistance activities CD003288 (2009).
long-term determinants of all-cause mortality — a is associated with improved physical function. This is a systematic Cochrane review of randomized
33-year follow-up of the Mini-Finland Health 248. Chen, H. T., Chung, Y. C., Chen, Y. J., Ho, S. Y. & Wu, H. J. and quasi-randomized controlled trials of oral
Examination Survey. Int. J. Obes. (Lond.) 38, Effects of different types of exercise on body protein and energy supplementation in older
1126–1132 (2014). composition, muscle strength, and IGF-1 in the elderly people, which shows a small but consistent weight
229. Hamer, M. & O’Donovan, G. Sarcopenic obesity, with sarcopenic obesity. J. Am. Geriatr. Soc. 65, gain in older people.
weight loss, and mortality: the English Longitudinal 827–832 (2017). 269. Brenner, B. M., Meyer, T. W. & Hostetter, T. H. Dietary
Study of Ageing. Am. J. Clin. Nutr. 106, 125–129 249. McTigue, K. M. et al. Screening and interventions for protein intake and the progressive nature of kidney
(2017). obesity in adults: summary of the evidence for the U.S. disease: the role of hemodynamically mediated
230. Tian, S. & Xu, Y. Association of sarcopenic obesity Preventive Services Task Force. Ann. Intern. Med. 139, glomerular injury in the pathogenesis of progressive
with the risk of all-cause mortality: a meta-analysis of 933–949 (2003). glomerular sclerosis in aging, renal ablation, and
prospective cohort studies. Geriatr. Gerontol. Int. 16, 250. Batsis, J. A. et al. Weight loss interventions in older intrinsic renal disease. N. Engl. J. Med. 307,
155–166 (2016). adults with obesity: a systematic review of randomized 652–659 (1982).
231. Newman, A. B. et al. Strength, but not muscle mass, is controlled trials since 2005. J. Am. Geriatr. Soc. 65, 270. Klahr, S. The modification of diet in renal disease
associated with mortality in the health, aging and 257–268 (2017). study. N. Engl. J. Med. 320, 864–866 (1989).
body composition study cohort. J. Gerontol. A Biol. This is a comprehensive systematic review of 271. Lentine, K. & Wrone, E. M. New insights into protein
Sci. Med. Sci. 61, 72–77 (2006). randomized trials in older adults with obesity intake and progression of renal disease. Curr. Opin.
This study demonstrates the importance of muscle highlighting the importance of the improvement in Nephrol. Hypertens. 13, 333–336 (2004).
strength as opposed to muscle mass as a key physical function through diet and exercise. 272. Pedrini, M. T., Levey, A. S., Lau, J., Chalmers, T. C. &
determinant of mortality. 251. Johnston, B. C. et al. Comparison of weight loss Wang, P. H. The effect of dietary protein restriction on
232. Rossi, A. P. et al. Dynapenic abdominal obesity as among named diet programs in overweight and obese the progression of diabetic and nondiabetic renal
predictor of mortality and disability worsening in older adults: a meta-analysis. JAMA 312, 923–933 (2014). diseases: a meta-analysis. Ann. Intern. Med. 124,
adults: a 10-year prospective study. Clin. Nutr. 35, 252. Dansinger, M. L., Gleason, J. A., Griffith, J. L., 627–632 (1996).
199–204 (2016). Selker, H. P. & Schaefer, E. J. Comparison of the 273. Bhasin, S. et al. Effect of protein intake on lean body
233. Moon, J. H. et al. Predictive values of the new Atkins, Ornish, Weight Watchers, and Zone diets for mass in functionally limited older men: a randomized
sarcopenia index by the Foundation for the National weight loss and heart disease risk reduction: a clinical trial. JAMA Intern. Med. 178, 530–541
Institutes of Health sarcopenia project for mortality randomized trial. JAMA 293, 43–53 (2005). (2018).
among older Korean adults. PLoS ONE 11, e0166344 253. Areta, J. L. et al. Reduced resting skeletal muscle protein 274. Garber, C. E. et al. American College of Sports
(2016). synthesis is rescued by resistance exercise and protein Medicine position stand. Quantity and quality of
234. Messier, V. et al. Metabolic profile and quality of ingestion following short-term energy deficit. Am. J. exercise for developing and maintaining
life in class I sarcopenic overweight and obese Physiol. Endocrinol. Metab. 306, E989–E997 (2014). cardiorespiratory, musculoskeletal, and neuromotor
postmenopausal women: a MONET study. Appl. 254. Pasiakos, S. M. et al. Effects of high-protein diets on fitness in apparently healthy adults: guidance for
Physiol. Nutr. Metab. 34, 18–24 (2009). fat-free mass and muscle protein synthesis following prescribing exercise. Med. Sci. Sports Exerc. 43,
235. Ware, J. et al. User’s Manual for the SF-36v2 Health weight loss: a randomized controlled trial. FASEB J. 1334–1359 (2011).
Survey (QualityMetric Incorporated, 2007). 27, 3837–3847 (2013). 275. Gillespie, L. D. et al. Interventions for preventing falls
236. Silva Neto, L. S., Karnikowiski, M. G., Tavares, A. B. & 255. Campbell, W. W. et al. Resistance training preserves in older people living in the community. Cochrane
Lima, R. M. Association between sarcopenia, fat-free mass without impacting changes in protein Database Syst. Rev. 9, CD007146 (2012).
sarcopenic obesity, muscle strength and quality of life metabolism after weight loss in older women. 276. Lin, X. et al. Effects of exercise training on
variables in elderly women. Rev. Bras. Fisioter. 16, Obesity (Silver Spring) 17, 1332–1339 (2009). cardiorespiratory fitness and biomarkers of
360–367 (2012). 256. Wolfe, R. R., Miller, S. L. & Miller, K. B. Optimal cardiometabolic health: a systematic review and
237. Pedrero-Chamizo, R. et al. Higher levels of physical protein intake in the elderly. Clin. Nutr. 27, 675–684 meta-analysis of randomized controlled trials. J. Am.
fitness are associated with a reduced risk of suffering (2008). Heart Assoc. 4, e002014 (2015).

Reviews
277. Hwang, C. L., Wu, Y. T. & Chou, C. H. Effect of aerobic 297. Liao, C. D. et al. Effects of elastic resistance exercise 318. Zibellini, J. et al. Does diet-induced weight loss lead to
interval training on exercise capacity and metabolic on body composition and physical capacity in older bone loss in overweight or obese adults? A systematic
risk factors in people with cardiometabolic disorders: women with sarcopenic obesity: a CONSORT- review and meta-analysis of clinical trials. J. Bone
a meta-analysis. J. Cardiopulm. Rehabil. Prev. 31, compliant prospective randomized controlled trial. Miner. Res. 30, 2168–2178 (2015).
378–385 (2011). Medicine (Baltimore) 96, e7115 (2017). 319. Soltani, S., Hunter, G. R., Kazemi, A. & Shab-Bidar, S.
278. Sui, X. M. et al. Cardiorespiratory fitness and adiposity 298. Weinheimer, E. M., Sands, L. P. & Campbell, W. W. A The effects of weight loss approaches on bone mineral
as mortality predictors in older adults. JAMA 298, systematic review of the separate and combined density in adults: a systematic review and meta-analysis
2507–2516 (2007). effects of energy restriction and exercise on fat-free of randomized controlled trials. Osteoporos. Int.
279. Taaffe, D. R., Duret, C., Wheeler, S. & Marcus, R. mass in middle-aged and older adults: implications for 27, 2655–2671 (2016).
Once-weekly resistance exercise improves muscle sarcopenic obesity. Nutr. Rev. 68, 375–388 (2010). 320. Colleluori, G., Napoli, N., Phadnis, U., Armamento-
strength and neuromuscular performance in older This is a systematic review assessing the effects of Villareal, R. & Villareal, D. T. Effect of weight loss,
adults. J. Am. Geriatr. Soc. 47, 1208–1214 (1999). energy restriction and exercise on fat-free mass exercise, or both on undercarboxylated osteocalcin
280. Brown, A. B., McCartney, N. & Sale, D. G. Positive and suggests that exercise is an effective tool in and insulin secretion in frail, obese older adults.
adaptations to weight-lifting training in the elderly. combating sarcopenia-induced weight loss. Oxid. Med. Cell. Longev. 2017, 4807046 (2017).
J. Appl. Physiol. (1985) 69, 1725–1733 (1990). 299. Armamento-Villareal, R., Aguirre, L. E., Qualls, C. & 321. Waters, D. L. et al. Long-term maintenance of weight
281. Liu, C. J. & Latham, N. K. Progressive resistance Villareal, D. T. Effect of lifestyle intervention on the loss after lifestyle intervention in frail, obese older
strength training for improving physical function in hormonal profile of frail, obese older men. J. Nutr. adults. J. Nutr. Health Aging 17, 3–7 (2013).
older adults. Cochrane Database Syst. Rev. 3, Health Aging 20, 334–340 (2016). 322. Villareal, D. T. et al. Effect of two-year caloric
CD002759 (2009). 300. Villareal, D. T. et al. Effect of lifestyle intervention on restriction on bone metabolism and bone mineral
This is a systematic Cochrane review of randomized metabolic coronary heart disease risk factors in obese density in non-obese younger adults: a randomized
controlled trials reporting physical outcomes of older adults. Am. J. Clin. Nutr. 84, 1317–1323 clinical trial. J. Bone Miner. Res. 31, 40–51 (2016).
progressive resistance therapy that demonstrates (2006). This is a 2-year randomized trial of caloric
improved strength and performance. 301. Bouchonville, M. et al. Weight loss, exercise or both restriction, which had been previously shown to
282. Pahor, M. et al. Effect of structured physical activity on and cardiometabolic risk factors in obese older adults: lead to bone loss at important sites of osteoporotic
prevention of major mobility disability in older adults: results of a randomized controlled trial. Int. J. Obes. fractures as represented by reductions in BMD.
the LIFE study randomized clinical trial. JAMA 311, (Lond.) 38, 423–431 (2014). 323. Villareal, D. T. et al. Reduced bone mineral density is
2387–2396 (2014). 302. Abbenhardt, C. et al. Effects of individual and combined not associated with significantly reduced bone quality
This study reports on a gold standard, structured, dietary weight loss and exercise interventions in in men and women practicing long-term calorie
long-term physical activity intervention, consisting postmenopausal women on adiponectin and leptin restriction with adequate nutrition. Aging Cell 10,
of 3–4 times of aerobic, resistance and flexibility levels. J. Intern. Med. 274, 163–175 (2013). 96–102 (2011).
training per week, that demonstrates improvements 303. Beavers, K. M. et al. Long-term physical activity and 324. Pop, L. C. et al. Moderate weight loss in obese and
in mobility disability over a 2.6-year follow-up. inflammatory biomarkers in older adults. Med. Sci. overweight men preserves bone quality. Am. J. Clin.
283. Stec, M. J. et al. Randomized, four-arm, dose-response Sports Exerc. 42, 2189–2196 (2010). Nutr. 101, 659–667 (2015).
clinical trial to optimize resistance exercise training 304. Kelly, K. R. et al. Lifestyle-induced decrease in fat mass 325. Johnson, K. C. et al. The effect of intentional weight
for older adults with age-related muscle atrophy. improves adiponectin secretion in obese adults. Med. loss on fracture risk in persons with diabetes: results
Exp. Gerontol. 99, 98–109 (2017). Sci. Sports Exerc. 46, 920–926 (2014). from the Look AHEAD randomized clinical trial.
284. Guralnik, J. M., Ferrucci, L., Simonsick, E. M., Salive, M. E. 305. Wang, X., You, T., Murphy, K., Lyles, M. F. & Nicklas, B. J. J. Bone Miner. Res. 32, 2278–2287 (2017).
& Wallace, R. B. Lower-extremity function in persons Addition of exercise increases plasma adiponectin and 326. Haywood, C. J. et al. Very low calorie diets for weight
over the age of 70 years as a predictor of subsequent release from adipose tissue. Med. Sci. Sports Exerc. 47, loss in obese older adults—a randomized trial.
disability. N. Engl. J. Med. 332, 556–561 (1995). 2450–2455 (2015). J. Gerontol. A Biol. Sci. Med. Sci. 73, 59–65 (2017).
285. Liu, C. K. et al. The impact of sarcopenia on a physical 306. O’Leary, V. B. et al. Enhanced adiponectin multimer 327. Shah, K. et al. Exercise training in obese older adults
activity intervention: the Lifestyle Interventions and ratio and skeletal muscle adiponectin receptor prevents increase in bone turnover and attenuates
Independence for Elders Pilot Study (LIFE-P). J. Nutr. expression following exercise training and diet in older decrease in hip bone mineral density induced by
Health Aging 18, 59–64 (2014). insulin-resistant adults. Am. J. Physiol. Endocrinol. weight loss despite decline in bone-active hormones.
286. Villanueva, M. G., Lane, C. J. & Schroeder, E. T. Short Metab. 293, E421–E427 (2007). J. Bone Miner. Res. 26, 2851–2859 (2011).
rest interval lengths between sets optimally enhance 307. Nicklas, B. J. et al. Diet-induced weight loss, exercise, 328. Armamento-Villareal, R. et al. Weight loss in obese
body composition and performance with 8 weeks of and chronic inflammation in older, obese adults: older adults increases serum sclerostin and impairs
strength resistance training in older men. Eur. J. Appl. a randomized controlled clinical trial. Am. J. Clin. Nutr. hip geometry but both are prevented by exercise
Physiol. 115, 295–308 (2015). 79, 544–551 (2004). training. J. Bone Miner. Res. 27, 1215–1221 (2012).
287. Ramirez-Campillo, R. et al. High-speed resistance This is an early trial suggesting that resistance 329. Moyer, V. A. Vitamin D and calcium supplementation to
training is more effective than low-speed resistance training is important for improving body prevent fractures in adults: U.S. Preventive Services Task
training to increase functional capacity and muscle composition and muscle strength in elderly Force recommendation statement. Ann. Intern. Med.
performance in older women. Exp. Gerontol. 58, individuals who are obese, an effect which is 158, 691–696 (2013).
51–57 (2014). improved with caloric restriction. 330. Anderson, J. J. et al. Calcium intake from diet and
288. Ramirez-Campillo, R. et al. Effects of different doses 308. Beavers, K. M., Ambrosius, W. T., Nicklas, B. J. & supplements and the risk of coronary artery
of high-speed resistance training on physical Rejeski, W. J. Independent and combined effects of calcification and its progression among older adults:
performance and quality of life in older women: a physical activity and weight loss on inflammatory 10-year follow-up of the multi-ethnic study of
randomized controlled trial. Clin. Interv. Aging 11, biomarkers in overweight and obese older adults. atherosclerosis (MESA). J. Am. Heart Assoc. 5,
1797–1804 (2016). J. Am. Geriatr. Soc. 61, 1089–1094 (2013). e003815 (2016).
289. Balachandran, A., Krawczyk, S. N., Potiaumpai, M. & 309. Zibellini, J. et al. Effect of diet-induced weight loss 331. Hassan-Smith, Z. K. et al. 25-hydroxyvitamin D3 and
Signorile, J. F. High-speed circuit training versus on muscle strength in adults with overweight or 1,25-dihydroxyvitamin D3 exert distinct effects on
hypertrophy training to improve physical function in obesity — a systematic review and meta-analysis of human skeletal muscle function and gene expression.
sarcopenic obese adults: a randomized controlled clinical trials. Obes. Rev. 17, 647–663 (2016). PLoS ONE 12, e0170665 (2017).
trial. Exp. Gerontol. 60, 64–71 (2014). 310. Gallagher, D. et al. Changes in skeletal muscle and 332. Beaudart, C. et al. The effects of vitamin D on skeletal
290. Vasconcelos, K. S. et al. Effects of a progressive organ size after a weight-loss intervention in muscle strength, muscle mass, and muscle power:
resistance exercise program with high-speed overweight and obese type 2 diabetic patients. Am. J. a systematic review and meta-analysis of randomized
component on the physical function of older women Clin. Nutr. 105, 78–84 (2017). controlled trials. J. Clin. Endocrinol. Metab. 99,
with sarcopenic obesity: a randomized controlled trial. 311. Weiss, E. P., Jordan, R. C., Frese, E. M., Albert, S. G. & 4336–4345 (2014).
Braz. J. Phys. Ther. 20, 432–440 (2016). Villareal, D. T. Effects of weight loss on lean mass, 333. Malafarina, V., Uriz-Otano, F., Malafarina, C.,
291. Son, N. K., Ryu, Y. U., Jeong, H. W., Jang, Y. H. & strength, bone, and aerobic capacity. Med. Sci. Sports Martinez, J. A. & Zulet, M. A. Effectiveness of
Kim, H. D. Comparison of 2 different exercise Exerc. 49, 206–217 (2017). nutritional supplementation on sarcopenia and
approaches: Tai Chi versus Otago, in community-dwelling 312. Wood, R. J. et al. Preservation of fat-free mass after recovery in hip fracture patients. A multi-centre
older women. J. Geriatr. Phys. Ther. 39, 51–57 (2016). two distinct weight loss diets with and without randomized trial. Maturitas 101, 42–50 (2017).
292. Huang, Z. G., Feng, Y. H., Li, Y. H. & Lv, C. S. progressive resistance exercise. Metab. Syndr. Relat. 334. American Geriatrics Society Workgroup on Vitamin D
Systematic review and meta-analysis: Tai Chi for Disord. 10, 167–174 (2012). Supplementation for Older Adults. Recommendations
preventing falls in older adults. BMJ Open 7, 313. Tang, X. et al. Obesity and risk of hip fracture in abstracted from the American Geriatrics Society
e013661 (2017). adults: a meta-analysis of prospective cohort studies. Consensus Statement on vitamin D for prevention of
293. Youkhana, S., Dean, C. M., Wolff, M., Sherrington, C. PLoS ONE 8, e55077 (2013). falls and their consequences. J. Am. Geriatr. Soc. 62,
& Tiedemann, A. Yoga-based exercise improves 314. Nielson, C. M. et al. BMI and fracture risk in older 147–152 (2014).
balance and mobility in people aged 60 and over: men: the osteoporotic fractures in men study (MrOS). 335. Bischoff-Ferrari, H. A. et al. Higher 25-hydroxyvitamin D
a systematic review and meta-analysis. Age Ageing 45, J. Bone Miner. Res. 26, 496–502 (2011). concentrations are associated with better lower-
21–29 (2016). 315. Compston, J. E. et al. Obesity is not protective against extremity function in both active and inactive persons
294. Waller, B. et al. The effect of aquatic exercise on fracture in postmenopausal women: GLOW. Am. J. Med. aged > or =60 y. Am. J. Clin. Nutr. 80, 752–758 (2004).
physical functioning in the older adult: a systematic 124, 1043–1050 (2011). 336. Scott, D. et al. A prospective study of the associations
review with meta-analysis. Age Ageing 45, 593–601 316. Ensrud, K. E. et al. A comparison of frailty indexes for between 25-hydroxy-vitamin D, sarcopenia
(2016). the prediction of falls, disability, fractures, and progression and physical activity in older adults. Clin.
295. Nobrega, S. R. & Libardi, C. A. Is resistance training to mortality in older men. J. Am. Geriatr. Soc. 57, Endocrinol. (Oxf.) 73, 581–587 (2010).
muscular failure necessary? Front. Physiol. 7, 10 492–498 (2009). 337. Wicherts, I. S. et al. Vitamin D status predicts physical
(2016). 317. Sundh, D. et al. A high amount of local adipose tissue performance and its decline in older persons. J. Clin.
296. Aguirre, L. E. & Villareal, D. T. Physical exercise as is associated with high cortical porosity and low bone Endocrinol. Metab. 92, 2058–2065 (2007).
therapy for frailty. Nestle Nutr. Inst. Workshop Ser. 83, material strength in older women. J. Bone Miner. Res. 338. Zittermann, A. et al. Vitamin D deficiency and
83–92 (2015). 31, 749–757 (2016). mortality risk in the general population:
Reviews
a meta-analysis of prospective cohort studies. Am. J. 362. Botero, J. P. et al. Effects of long-term periodized 382. Apovian, C., Palmer, K., Fain, R., Perdomo, C. &
Clin. Nutr. 95, 91–100 (2012). resistance training on body composition, leptin, Rubino, D. Effects of lorcaserin on fat and lean mass
339. Anker, S. D., Morley, J. E. & von Haehling, S. Welcome resistin and muscle strength in elderly post- loss in obese and overweight patients without
to the ICD-10 code for sarcopenia. J. Cachexia menopausal women. J. Sports Med. Phys. Fitness 53, and with type 2 diabetes mellitus: the BLOSSOM and
Sarcopenia Muscle 7, 512–514 (2016). 289–294 (2013). BLOOM-DM studies. Diabetes Obes. Metab. 18,
340. Cao, B. Future healthy life expectancy among older 363. Ebersbach, G., Edler, D., Kaufhold, O. & Wissel, J. 945–948 (2016).
adults in the US: a forecast based on cohort smoking Whole body vibration versus conventional 383. Simko, J. et al. The effect of topiramate
and obesity history. Popul. Health Metr. 14, 23 (2016). physiotherapy to improve balance and gait in and lamotrigine on rat bone mass, structure and
341. U.S. Preventive Services Task Force. Screening for Parkinson’s disease. Arch. Phys. Med. Rehabil. 89, metabolism. J. Neurol. Sci. 340, 80–85 (2014).
osteoporosis: U.S. preventive services task force 399–403 (2008). 384. Eliasson, B. et al. Weight loss and metabolic effects of
recommendation statement. Ann. Intern. Med. 154, 364. Zhang, L. et al. Effect of whole-body vibration exercise topiramate in overweight and obese type 2 diabetic
356–364 (2011). on mobility, balance ability and general health status patients: randomized double-blind placebo-controlled
342. Maddalo, M. et al. Validation of a free software for in frail elderly patients: a pilot randomized controlled trial. Int. J. Obes. (Lond.) 31, 1140–1147 (2007).
unsupervised assessment of abdominal fat in MRI. trial. Clin. Rehabil. 28, 59–68 (2014). 385. Yaman, M. et al. Effects of topiramate use on body
Phys. Med. 37, 24–31 (2017). 365. Rogan, S., Hilfiker, R., Herren, K., Radlinger, L. & composition and resting metabolic rate in migraine
343. van Vugt, J. L. A. et al. A comparative study of de Bruin, E. D. Effects of whole-body vibration on patients. Neurol. Sci. 34, 225–229 (2013).
software programmes for cross-sectional skeletal postural control in elderly: a systematic review and 386. Cordero-MacIntyre, Z. R. et al. Effect of a
muscle and adipose tissue measurements on meta-analysis. BMC Geriatr. 11, 72 (2011). weight-reduction program on total and regional body
abdominal computed tomography scans of rectal 366. Rogan, S. et al. Feasibility and effects of applying composition in obese postmenopausal women.
cancer patients. J. Cachexia Sarcopenia Muscle 8, stochastic resonance whole-body vibration on Ann. NY Acad. Sci. 904, 526–535 (2000).
285–297 (2017). untrained elderly: a randomized crossover pilot study. 387. Gadde, K. M., Zhang, W. & Foust, M. S. Bupropion
344. Curtis, J. R. et al. The geographic availability and BMC Geriatr. 15, 25 (2015). treatment of olanzapine-associated weight gain:
associated utilization of dual-energy X-ray 367. Verschueren, S. M. et al. The effects of whole-body an open-label, prospective trial. J. Clin.
absorptiometry (DXA) testing among older persons in vibration training and vitamin D supplementation on Psychopharmacol. 26, 409–413 (2006).
the United States. Osteoporos. Int. 20, 1553–1561 muscle strength, muscle mass, and bone density in 388. Smith, S. R. et al. Combination therapy with
(2009). institutionalized elderly women: a 6-month naltrexone and bupropion for obesity reduces total
345. Maggio, M. et al. Instrumental and non-instrumental randomized, controlled trial. J. Bone Miner. Res. 26, and visceral adiposity. Diabetes Obes. Metab. 15,
evaluation of 4-meter walking speed in older 42–49 (2011). 863–866 (2013).
individuals. PLoS ONE 11, e0153583 (2016). 368. Cardim, A. B. et al. Does whole-body vibration 389. Kujawska-Luczak, M. et al. The effect of orlistat versus
346. Nascimento, L. R. et al. Different instructions during the improve the functional exercise capacity of subjects metformin on body composition and insulin resistance
ten-meter walking test determined significant increases with COPD? A meta-analysis. Respir. Care 61, in obese premenopausal women: 3-month randomized
in maximum gait speed in individuals with chronic 1552–1559 (2016). prospective open-label study. Arch. Med. Sci. 13,
hemiparesis. Rev. Bras. Fisioter. 16, 122–127 (2012). 369. Burke, D. & Schiller, H. H. Discharge pattern of single 725–731 (2017).
347. Roberts, H. C. et al. A review of the measurement of motor units in the tonic vibration reflex of human 390. Smith, S. R. et al. Orlistat 60 mg reduces visceral
grip strength in clinical and epidemiological studies: triceps surae. J. Neurol. Neurosurg. Psychiatry 39, adipose tissue: a 24-week randomized, placebo-
towards a standardised approach. Age Ageing 40, 729–741 (1976). controlled, multicenter trial. Obesity (Silver Spring)
423–429 (2011). 370. Chen, H., Ma, J., Lu, B. & Ma, X. L. The effect of 19, 1796–1803 (2011).
348. Witard, O. C., McGlory, C., Hamilton, D. L. & whole-body vibration training on lean mass: 391. Smith, T. J. et al. Efficacy of orlistat 60 mg on weight
Phillips, S. M. Growing older with health and vitality: a PRISMA-compliant meta-analysis. Medicine loss and body fat mass in US Army soldiers. J. Acad.
a nexus of physical activity, exercise and nutrition. (Baltimore) 96, e8390 (2017). Nutr. Diet. 112, 533–540 (2012).
Biogerontology 17, 529–546 (2016). 371. Lau, R. W. et al. The effects of whole body vibration 392. Batsis, J. A. & Dolkart, K. M. Evaluation of older adults
349. Garatachea, N. et al. Exercise attenuates the major therapy on bone mineral density and leg muscle with obesity for bariatric surgery: geriatricians’
hallmarks of aging. Rejuvenation Res. 18, 57–89 (2015). strength in older adults: a systematic review and perspective. J. Clin. Gerontol. Geriatr. 6, 45–53 (2015).
350. Emmelot-Vonk, M. H. et al. Effect of testosterone meta-analysis. Clin. Rehabil. 25, 975–988 (2011). 393. Mastino, D. et al. Bariatric surgery outcomes in
supplementation on functional mobility, cognition, 372. Bogaerts, A. et al. Impact of whole-body vibration sarcopenic obesity. Obes. Surg. 26, 2355–2362 (2016).
and other parameters in older men: a randomized training versus fitness training on muscle strength and 394. Cole, A. J. et al. Long-term body composition changes
controlled trial. JAMA 299, 39–52 (2008). muscle mass in older men: a 1-year randomized in women following roux-en-Y gastric bypass surgery.
351. Travison, T. G. et al. Clinical meaningfulness of the controlled trial. J. Gerontol. A Biol. Sci. Med. Sci. 62, JPEN J. Parenter. Enteral Nutr. 41, 583–591 (2017).
changes in muscle performance and physical function 630–635 (2007). 395. Anderwald, C. H. et al. Alterations in gastrointestinal,
associated with testosterone administration in older 373. Chang, S. F., Lin, P. C., Yang, R. S. & Yang, R. J. The endocrine, and metabolic processes after bariatric
men with mobility limitation. J. Gerontol. A Biol. Sci. preliminary effect of whole-body vibration intervention Roux-en-Y gastric bypass surgery. Diabetes Care 35,
Med. Sci. 66, 1090–1099 (2011). on improving the skeletal muscle mass index, physical 2580–2587 (2012).
352. Nguyen, H. Q. et al. Health care use and costs fitness, and quality of life among older people with 396. Lyytinen, T., Liikavainio, T., Paakkonen, M., Gylling, H.
associated with use of a health club membership sarcopenia. BMC Geriatr. 18, 17 (2018). & Arokoski, J. P. Physical function and properties of
benefit in older adults with diabetes. Diabetes Care 374. Bemben, D. A., Palmer, I. J., Bemben, M. G. & quadriceps femoris muscle after bariatric surgery and
31, 1562–1567 (2008). Knehans, A. W. Effects of combined whole-body subsequent weight loss. J. Musculoskelet. Neuronal
353. Bergamin, M. et al. Water- versus land-based exercise vibration and resistance training on muscular strength Interact. 13, 329–338 (2013).
in elderly subjects: effects on physical performance and bone metabolism in postmenopausal women. 397. Thibault, R., Huber, O., Azagury, D. E. & Pichard, C.
and body composition. Clin. Interv. Aging 8, Bone 47, 650–656 (2010). Twelve key nutritional issues in bariatric surgery.
1109–1117 (2013). 375. Fjeldstad, C., Palmer, I. J., Bemben, M. G. & Clin. Nutr. 35, 12–17 (2016).
354. de Souza Vasconcelos, K. S. et al. Land-based versus Bemben, D. A. Whole-body vibration augments 398. Vaurs, C. et al. Determinants of changes in muscle
aquatic resistance therapeutic exercises for older resistance training effects on body composition in mass after bariatric surgery. Diabetes Metab. 41,
women with sarcopenic obesity: study protocol for a postmenopausal women. Maturitas 63, 79–83 (2009). 416–421 (2015).
randomised controlled trial. Trials 14, 296 (2013). 376. Machado, A., Garcia-Lopez, D., Gonzalez-Gallego, J. & 399. Coates, P. S., Fernstrom, J. D., Fernstrom, M. H.,
355. Simmons, V. & Hansen, P. D. Effectiveness of water Garatachea, N. Whole-body vibration training Schauer, P. R. & Greenspan, S. L. Gastric bypass
exercise on postural mobility in the well elderly: increases muscle strength and mass in older women: surgery for morbid obesity leads to an increase in
an experimental study on balance enhancement. a randomized-controlled trial. Scand. J. Med. Sci. bone turnover and a decrease in bone mass. J. Clin.
J. Gerontol. A Biol. Sci. Med. Sci. 51, M233–M238 Sports 20, 200–207 (2010). Endocrinol. Metab. 89, 1061–1065 (2004).
(1996). 377. von Stengel, S., Kemmler, W., Engelke, K. & 400. Ko, B. J. et al. Relationship between bariatric surgery
356. Li, F. et al. An evaluation of the effects of Tai Chi Kalender, W. A. Effect of whole-body vibration on and bone mineral density: a meta-analysis. Obes. Surg.
exercise on physical function among older persons: neuromuscular performance and body composition for 26, 1414–1421 (2016).
a randomized contolled trial. Ann. Behav. Med. 23, females 65 years and older: a randomized-controlled 401. Shanbhogue, V. V. et al. Bone structural changes
139–146 (2001). trial. Scand. J. Med. Sci. Sports 22, 119–127 (2012). after gastric bypass surgery evaluated by HR-pQCT:
357. Hildreth, K. L. et al. Effects of testosterone and 378. Cristi-Montero, C., Cuevas, M. J. & Collado, P. S. a two-year longitudinal study. Eur. J. Endocrinol. 176,
progressive resistance exercise in healthy, highly Whole-body vibration training as complement to 685–693 (2017).
functioning older men with low-normal testosterone programs aimed at weight loss. Nutr. Hosp. 28, 402. Yu, E. W., Lee, M. P., Landon, J. E., Lindeman, K. G. &
levels. J. Clin. Endocrinol. Metab. 98, 1891–1900 1365–1371 (2013). Kim, S. C. Fracture risk after bariatric surgery: roux-en-Y
(2013). 379. Lamont, H. S. et al. Effects of a 6-week periodized gastric bypass versus adjustable gastric banding.
358. Strohacker, K., Fazzino, D., Breslin, W. L. & Xu, X. squat training with or without whole-body vibration J. Bone Miner. Res. 32, 1229–1236 (2017).
The use of periodization in exercise prescriptions for upon short-term adaptations in squat strength and 403. Cohen, P. G. Obesity in men: the hypogonadal-
inactive adults: a systematic review. Prev. Med. Rep. body composition. J. Strength Cond. Res. 25, estrogen receptor relationship and its effect on
2, 385–396 (2015). 1839–1848 (2011). glucose homeostasis. Med. Hypotheses 70, 358–360
359. Steele, J. Intensity; in-ten-si-ty; noun. 1. Often used 380. Wei, N., Pang, M. Y., Ng, S. S. & Ng, G. Y. Optimal (2008).
ambiguously within resistance training. 2. Is it time to frequency/time combination of whole-body vibration 404. Freeman, E. W., Sammel, M. D., Lin, H. & Gracia, C. R.
drop the term altogether? Br. J. Sports Med. 48, training for improving muscle size and strength of Obesity and reproductive hormone levels in the
1586–1588 (2014). people with age-related muscle loss (sarcopenia): transition to menopause. Menopause 17, 718–726
360. Conlon, J. A. et al. Periodization strategies in older a randomized controlled trial. Geriatr. Gerontol. Int. (2010).
adults: impact on physical function and health. Med. 17, 1412–1420 (2017). 405. Nettleship, J. E., Pugh, P. J., Channer, K. S., Jones, T. &
Sci. Sports Exerc. 48, 2426–2436 (2016). 381. Perna, S. et al. Liraglutide and obesity in elderly: Jones, R. D. Inverse relationship between serum levels
361. Prestes, J. et al. Understanding the individual efficacy in fat loss and safety in order to prevent of interleukin-1beta and testosterone in men with
responsiveness to resistance training periodization. sarcopenia. A perspective case series study. stable coronary artery disease. Horm. Metab. Res. 39,
Age (Dordr.) 37, 9793 (2015). Aging Clin. Exp. Res. 28, 1251–1257 (2016). 366–371 (2007).

Reviews
406. Corrales, J. J. et al. Androgen-replacement therapy cellular and molecular action mechanisms underlying 446. Camporez, J. P. et al. Anti-myostatin antibody
depresses the ex vivo production of inflammatory the anabolic actions. Cell. Mol. Life Sci. 69, increases muscle mass and strength and improves
cytokines by circulating antigen-presenting cells in 1651–1667 (2012). insulin sensitivity in old mice. Proc. Natl Acad. Sci.
aging type-2 diabetic men with partial androgen 427. Crawford, J. et al. Study design and rationale for the USA 113, 2212–2217 (2016).
deficiency. J. Endocrinol. 189, 595–604 (2006). phase 3 clinical development program of enobosarm, This study evaluates a treatment consisting of anti-
407. Neto, W. K. et al. Effects of testosterone on lean a selective androgen receptor modulator, for the myostatin antibody administration for 4 weeks,
mass gain in elderly men: systematic review with prevention and treatment of muscle wasting in cancer showing improved muscle mass and strength in
meta-analysis of controlled and randomized studies. patients (POWER Trials). Curr. Oncol. Rep. 18, 37 young and old mice.
Age (Dordr.) 37, 9742 (2015). (2016). 447. Dong, J. et al. Inhibition of myostatin in mice improves
This is a meta-analysis demonstrating that 428. Dobs, A. S. et al. Effects of enobosarm on muscle insulin sensitivity via irisin-mediated cross talk
testosterone supplementation in elderly men leads wasting and physical function in patients with cancer: between muscle and adipose tissues. Int. J. Obes.
to increases in lean mass and potentially a double-blind, randomised controlled phase 2 trial. (Lond.) 40, 434–442 (2016).
reductions in fat mass. Lancet Oncol. 14, 335–345 (2013). 448. Buehring, B. & Binkley, N. Myostatin — the holy grail
408. Giannoulis, M. G. et al. The effects of growth 429. Dalton, J. T. et al. The selective androgen receptor for muscle, bone, and fat? Curr. Osteoporos. Rep. 11,
hormone and/or testosterone in healthy elderly men: modulator GTx-024 (enobosarm) improves lean body 407–414 (2013).
a randomized controlled trial. J. Clin. Endocrinol. mass and physical function in healthy elderly men and 449. Santos, A. R. et al. Different resistance-training
Metab. 91, 477–484 (2006). postmenopausal women: results of a double-blind, regimens evoked a similar increase in myostatin
409. Schroeder, E. T. et al. Value of measuring muscle placebo-controlled phase II trial. J. Cachexia inhibitors expression. Int. J. Sports Med. 36,
performance to assess changes in lean mass with Sarcopenia Muscle 2, 153–161 (2011). 761–768 (2015).
testosterone and growth hormone supplementation. 430. Papanicolaou, D. A. et al. A phase IIA randomized, 450. Sato, Y., Honda, Y., Kuno, H. & Oizumi, K.
Eur. J. Appl. Physiol. 112, 1123–1131 (2012). placebo-controlled clinical trial to study the efficacy Menatetrenone ameliorates osteopenia in disuse-
410. Hyde, Z. et al. Low free testosterone predicts frailty in and safety of the selective androgen receptor affected limbs of vitamin D− and K-deficient stroke
older men: the health in men study. J. Clin. Endocrinol. modulator (SARM), MK-0773 in female participants patients. Bone 23, 291–296 (1998).
Metab. 95, 3165–3172 (2010). with sarcopenia. J. Nutr. Health Aging 17, 533–543 451. Schurgers, L. J. & Vermeer, C. Determination of
411. Krasnoff, J. B. et al. Free testosterone levels are (2013). phylloquinone and menaquinones in food. Effect
associated with mobility limitation and physical 431. Bhattacharya, I. et al. Safety, pharmacokinetic, and of food matrix on circulating vitamin K concentrations.
performance in community-dwelling men: the pharmacodynamic evaluation after single and multiple Haemostasis 30, 298–307 (2000).
Framingham Offspring Study. J. Clin. Endocrinol. ascending doses of a novel selective androgen 452. Hart, J. P. et al. Electrochemical detection of depressed
Metab. 95, 2790–2799 (2010). receptor modulator in healthy subjects. Clin. Ther. 38, circulating levels of vitamin K1 in osteoporosis. J. Clin.
412. Storer, T. W. et al. Effects of testosterone 1401–1416 (2016). Endocrinol. Metab. 60, 1268–1269 (1985).
supplementation for 3 years on muscle performance 432. Watanabe, K. et al. BA321, a novel carborane analog 453. Bitensky, L. et al. Circulating vitamin K levels in
and physical function in older men. J. Clin. Endocrinol. that binds to androgen and estrogen receptors, acts patients with fractures. J. Bone Joint Surg. Br. 70,
Metab. 102, 583–593 (2017). as a new selective androgen receptor modulator of 663–664 (1988).
413. Saad, F., Rohrig, G., von Haehling, S. & Traish, A. bone in male mice. Biochem. Biophys. Res. Commun. 454. Hodges, S. J., Akesson, K., Vergnaud, P., Obrant, K. &
Testosterone deficiency and testosterone treatment in 478, 279–285 (2016). Delmas, P. D. Circulating levels of vitamins K1 and K2
older men. Gerontology 63, 144–156 (2017). 433. Saeed, A. et al. 2-Chloro-4-[[(1R,2R)-2-hydroxy- decreased in elderly women with hip fracture. J. Bone
414. Bhasin, S. et al. Older men are as responsive as young 2-methyl-cyclopentyl]amino]-3-methyl-benzonitrile: Miner. Res. 8, 1241–1245 (1993).
men to the anabolic effects of graded doses of a transdermal selective androgen receptor modulator 455. Hodges, S. J. et al. Depressed levels of circulating
testosterone on the skeletal muscle. J. Clin. (SARM) for muscle atrophy. J. Med. Chem. 59, menaquinones in patients with osteoporotic fractures
Endocrinol. Metab. 90, 678–688 (2005). 750–755 (2016). of the spine and femoral neck. Bone 12, 387–389
This is a randomized trial of dose-dependent 434. von Haehling, S. & Anker, S. D. Treatment of cachexia: (1991).
testosterone supplementation that demonstrates an overview of recent developments. Int. J. Cardiol. 456. Binkley, N. et al. Vitamin K treatment reduces
that older men are as responsive as young men to 184, 736–742 (2015). undercarboxylated osteocalcin but does not alter
the anabolic effects of testosterone; however, older 435. Garcia, J. M. & Polvino, W. J. Pharmacodynamic bone turnover, density, or geometry in healthy
men have lower testosterone clearance rates, hormonal effects of anamorelin, a novel oral ghrelin postmenopausal North American women. J. Bone
higher increments in haemoglobin and a higher mimetic and growth hormone secretagogue in healthy Miner. Res. 24, 983–991 (2009).
frequency of adverse effects. volunteers. Growth Horm. IGF Res. 19, 267–273 457. Binkley, N. C. & Suttie, J. W. Vitamin K nutrition and
415. Srinivas-Shankar, U. et al. Effects of testosterone on (2009). osteoporosis. J. Nutr. 125, 1812–1821 (1995).
muscle strength, physical function, body composition, 436. Garcia, J. M. & Polvino, W. J. Effect on body weight 458. Caillot-Augusseau, A. et al. Space flight is associated
and quality of life in intermediate-frail and frail elderly and safety of RC-1291, a novel, orally available ghrelin with rapid decreases of undercarboxylated osteocalcin
men: a randomized, double-blind, placebo-controlled mimetic and growth hormone secretagogue: results of and increases of markers of bone resorption without
study. J. Clin. Endocrinol. Metab. 95, 639–650 (2010). a phase I, randomized, placebo-controlled, multiple- changes in their circadian variation: observations in
416. Page, S. T. et al. Exogenous testosterone (T) alone or with dose study in healthy volunteers. Oncologist 12, two cosmonauts. Clin. Chem. 46, 1136–1143 (2000).
finasteride increases physical performance, grip strength, 594–600 (2007). 459. Douglas, A. S. et al. Carboxylation of osteocalcin in
and lean body mass in older men with low serum T. J. 437. Koshinaka, K. et al. Therapeutic potential of ghrelin post-menopausal osteoporotic women following
Clin. Endocrinol. Metab. 90, 1502–1510 (2005). treatment for unloading-induced muscle atrophy in vitamin K and D supplementation. Bone 17, 15–20
417. Ottenbacher, K. J., Ottenbacher, M. E., Ottenbacher, A. J., mice. Biochem. Biophys. Res. Commun. 412, (1995).
Acha, A. A. & Ostir, G. V. Androgen treatment and 296–301 (2011). 460. Macdonald, H. M. et al. Vitamin K1 intake is
muscle strength in elderly men: a meta-analysis. 438. Nishie, K., Yamamoto, S., Nagata, C., Koizumi, T. & associated with higher bone mineral density and
J. Am. Geriatr. Soc. 54, 1666–1673 (2006). Hanaoka, M. Anamorelin for advanced non-small-cell reduced bone resorption in early postmenopausal
418. O’Connell, M. D. et al. Do the effects of testosterone lung cancer with cachexia: systematic review and Scottish women: no evidence of gene-nutrient
on muscle strength, physical function, body meta-analysis. Lung Cancer 112, 25–34 (2017). interaction with apolipoprotein E polymorphisms.
composition, and quality of life persist six months after 439. Bai, Y. et al. Anamorelin for cancer anorexia-cachexia Am. J. Clin. Nutr. 87, 1513–1520 (2008).
treatment in intermediate-frail and frail elderly men? syndrome: a systematic review and meta-analysis. 461. Jamal, S. A., Browner, W. S., Bauer, D. C. &
J. Clin. Endocrinol. Metab. 96, 454–458 (2011). Support. Care Cancer 25, 1651–1659 (2017). Cummings, S. R. Warfarin use and risk for
419. Ng Tang Fui, M. et al. Effects of testosterone This is a meta-analysis of four randomized trials osteoporosis in elderly women. Study of Osteoporotic
treatment on body fat and lean mass in obese men demonstrating that lean body mass improved with Fractures Research Group. Ann. Intern. Med. 128,
on a hypocaloric diet: a randomised controlled trial. anamorelin, a novel ghrelin receptor agonist. 829–832 (1998).
BMC Med. 14, 153 (2016). 440. Garcia, J. M. et al. Anamorelin for patients with cancer 462. Yonemura, K., Kimura, M., Miyaji, T. & Hishida, A.
420. Ohlander, S. J., Varghese, B. & Pastuszak, A. W. cachexia: an integrated analysis of two phase 2, Short-term effect of vitamin K administration on
Erythrocytosis following testosterone therapy. randomised, placebo-controlled, double-blind trials. prednisolone-induced loss of bone mineral density in
Sex. Med. Rev. 6, 77–85 (2018). Lancet Oncol. 16, 108–116 (2015). patients with chronic glomerulonephritis. Calcif. Tissue
421. Albert, S. G. & Morley, J. E. Testosterone therapy, 441. Temel, J. S. et al. Anamorelin in patients with non-small- Int. 66, 123–128 (2000).
association with age, initiation and mode of therapy cell lung cancer and cachexia (ROMANA 1 and 463. Yoshida, M. et al. Effect of vitamin K supplementation
with cardiovascular events: a systematic review. ROMANA 2): results from two randomised, double-blind, on insulin resistance in older men and women.
Clin. Endocrinol. (Oxf.) 85, 436–443 (2016). phase 3 trials. Lancet Oncol. 17, 519–531 (2016). Diabetes Care 31, 2092–2096 (2008).
422. Martinez, C. et al. Testosterone treatment and risk 442. Katakami, N. et al. Anamorelin (ONO-7643) for the 464. Shea, M. K., Dawson-Hughes, B., Gundberg, C. M. &
of venous thromboembolism: population based treatment of patients with non-small cell lung cancer Booth, S. L. Reducing undercarboxylated osteocalcin
case-control study. BMJ 355, i5968 (2016). and cachexia: results from a randomized, double-blind, with vitamin k supplementation does not promote lean
423. Basaria, S. et al. Adverse events associated with placebo-controlled, multicenter study of Japanese tissue loss or fat gain over 3 years in older women and
testosterone administration. N. Engl. J. Med. 363, patients (ONO-7643-04). Cancer 124, 606–616 men: a randomized controlled trial. J. Bone Miner. Res.
109–122 (2010). (2018). 32, 243–249 (2017).
424. Morgentaler, A. et al. Fundamental concepts 443. Bergen, H. R. III et al. Myostatin as a mediator of 465. Shah, K., Gleason, L. & Villareal, D. T. Vitamin K and
regarding testosterone deficiency and treatment: sarcopenia versus homeostatic regulator of muscle bone health in older adults. J. Nutr. Gerontol. Geriatr.
international expert consensus resolutions. Mayo Clin. mass: insights using a new mass spectrometry-based 33, 10–22 (2014).
Proc. 91, 881–896 (2016). assay. Skelet. Muscle 5, 21 (2015). 466. Collins, C. A. et al. Stem cell function, self-renewal, and
425. Bhasin, S. et al. Testosterone therapy in men with 444. McPherron, A. C., Lawler, A. M. & Lee, S. J. Regulation behavioral heterogeneity of cells from the adult
androgen deficiency syndromes: an Endocrine Society of skeletal muscle mass in mice by a new TGF-beta muscle satellite cell niche. Cell 122, 289–301 (2005).
clinical practice guideline. J. Clin. Endocrinol. Metab. superfamily member. Nature 387, 83–90 (1997). 467. Sacco, A., Doyonnas, R., Kraft, P., Vitorovic, S. &
95, 2536–2559 (2010). 445. White, T. A. & LeBrasseur, N. K. Myostatin and Blau, H. M. Self-renewal and expansion of single
426. Dubois, V., Laurent, M., Boonen, S., Vanderschueren, D. sarcopenia: opportunities and challenges — a transplanted muscle stem cells. Nature 456,
& Claessens, F. Androgens and skeletal muscle: mini-review. Gerontology 60, 289–293 (2014). 502–506 (2008).
Reviews
468. Tompkins, B. A. et al. Allogeneic mesenchymal stem reported in this publication was supported in part by the US the official position of the Centers for Disease Control
cells ameliorate aging frailty: a phase ii randomized, National Institute on Aging of the US National Institutes of and Prevention.
double-blind, placebo-controlled clinical trial. Health under award number K23AG051681. Support was
J. Gerontol. A Biol. Sci. Med. Sci. 72, 1513–1522 (2017). also provided by the Dartmouth Health Promotion and Author contributions
469. Newman, A. B. et al. Sarcopenia: alternative Disease Prevention Research Center supported by cooper- J.A.B. and D.T.V. both researched the data for the article, pro-
definitions and associations with lower extremity ative agreement number U48DP005018 from the Centers vided substantial contributions to discussion of the content,
function. J. Am. Geriatr. Soc. 51, 1602–1609 (2003). for Disease Control and Prevention and the Dartmouth wrote the article and reviewed and/or edited the manuscript
This evaluates two sarcopenia definitions in the Clinical and Translational Science Institute under award before submission.
Health, Aging and Body Composition study and number UL1TR001086 from the US National Center for
Competing interests
suggests differential prevalence rates by obesity Advancing Translational Sciences. D.T.V.’s research was sup-
The authors declare no competing interests.
status, highlighting the importance of fat mass in ported in part by DK109950 from the US National Institute
the evaluation of sarcopenia. of Diabetes, Digestive and Kidney Diseases, AG031176 Publisher’s note
470. Baumgartner, R. N. Body composition in healthy from the US National Institutes on Aging, CX000906 from Springer Nature remains neutral with regard to jurisdictional
aging. Ann. NY Acad. Sci. 904, 437–448 (2000). the Veterans Affairs Office of Research and Development, claims in published maps and institutional affiliations.
1-14-LLY-38 from the American Diabetes Association and
Acknowledgements the Alkek Foundation. The content is solely the responsibil- Reviewer information
The authors would like to thank R. Masutani and R. Dokko ity of the authors and does not necessarily represent the Nature Reviews Endocrinology thanks W. Kemmler and the
for their help with preparing the manuscript and E. Weiss for official views of the US National Institutes of Health or other anonymous reviewer(s) for their contribution to
contributing to the images in figure 2. J.A.B.’s research of the Department of Veterans Affairs, nor represents the peer review of this work.


Sarcopenic Obesity in Older Adults

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REVIEWS

Sarcopenic obesity in older adults:

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Overeating Lack of exercise

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part a part b Sarcopenia (IWGS) provided a consensus definition for

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Table 1 | Selected definitions of sarcopenia with or without obesity

Table 1 (cont.) | Selected definitions of sarcopenia with or without obesity

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Quadriceps muscle area

Table 2 | Potential approved therapies in sarcopenic obesity

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Change from baseline (%)

Change from baseline (%)

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Skeletal muscle index

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