The science of longevity: here’s what we know

Active ageing, Longevity science

Article by Alberto Beretta Presidente e Direttore Scientifico di SoLongevity
The science of longevity
How and how long we live depends not only on our genes. Several studies have
shown that there are epigenetic  mechanisms that can repair DNA damage,
increase longevity and reduce the risk of disease. Here is what we know today In
the last century the average lifespan has almost doubled from 46 to 75 years, and
is expected to exceed 85 years in 2050. This change is due to a number of
concomitant factors: over 50 years of absence of major conflicts, economic
progress that has allowed access to uncomparable levels of nutrition and hygiene,
and unprecedented medical and scientific progress. Yet there is still room for
improvement: it is estimated that our organism has the intrinsic capacity to live
115-120 years. The improvement in lifespan has raised the issue of quality of
life in a larger segment of the population, from the increased incidence of chronic
and degenerative diseases to the loss of functional capacities coincident with a
growing demand for maintaining professional capabilities and social fulfilment.
Can we reach an advanced age without getting old? Recent studies suggest we
can.
Epigenetic aging
The big question today is: can we reach an advanced age without getting old?
Without losing our physical and cognitive abilities, maintaining our current level
of performance and, perhaps, recovering what we have lost? Studies conducted
in recent years in the field of the biology of aging suggest that we can. 
 A fundamental step in aging well is linked to epigenetics (which literally means
“above genetics”). What is written in our genetic code does not inevitably dictates
how we live: genes, the functional units of our DNA, can be more or less
expressed.
Epigenetics is the set of all those processes that, without modifying the DNA
sequence, regulate gene expression. The implementation of this genetic potential
therefore depends on epigenetics which in some cases confers advantages but in
others increases the risks. Just think of the conditions for which familiarity exists,
such as hypertension or type 2 diabetes: there is a genetic predisposition, but in
many cases it is our lifestyle that determines whether we will become
hypertensive or diabetic.
Epigenetics is easily influenceable and research has already discovered how to do
it.
How does the relationship between epigenetics and DNA work? Each cell is like a
small factory that works continuously to produce everything our body needs, and
to govern the biochemical reactions and processes that take place in it. All of this
thanks to the proteins, which are the structural “bricks” of the cells and regulate
the functioning of the entire organism. Proteins are made up of a long chain
of amino acids Amino acids are the basic substances that make up proteins. Each
protein is characterized by a precise sequence of amino acid "bricks". Some are
produced by the body by processing food, others, which the body cannot
synthesize, must be taken directly with food., the sequence of which is dictated
by the genes (the DNA units we inherit from our parents) that determine their
form and function. How does the relationship between epigenetics and DNA
work? DNA, however, is not immune to stimuli and attacks from the
environment: pollution, ionizing radiation, viruses, and bacteria, can cause
alterations that lead to defective biochemical reactions: micro-damages that
accumulate over the years, giving rise to degenerative processes typical of
aging. Epigenetic aging is now considered to be the common mechanism of all the
imbalances that lead to the gradual loss of our longevity reserve 
 Our organism possesses remarkable capacities of DNA self-repair and adaptation,
thanks mainly to the epigenetic mechanisms. It is when these mechanisms stop
working that we speak of epigenetic aging, which is considered the basis of the
gradual loss of the physiological reserve (which we call “longevity reserve“) with
which we are born and which represents our potential to live in good health for a
long time. Many aging mechanisms So far 9 key mechanisms (hallmarks) of aging
have been identified and epigenetics plays a major role. Epigenetic aging is closely
related to all the other hallmarks of aging, such as metabolic, immune and
cognitive aging, depending on the system we consider. It is also beleived that
improvement of only one of these 9 hallamrks, can impinge in all the others
leading to a rebalance of the whole system. DNA vs Epigenetics What matters the
most? Gene variants (or polymorphisms, i.e. genes that differ by a single letter in
the DNA sequence within a population) have been identified that can accelerate
or slow down aging. Carrying a gene variant that accelerates aging is not
necessarily bad news. The understanding of epigenetic mechanisms has made it
clear, however, that being a carrier of an unfavorable variant is not necessarily
bad news, because epigenetics can “limit the damage”. And even when the
variant is favourable, epigenetics continues to be important.  Blue Zones are well
defined geographical areas with high percentages of centenarians. The key pillar
is certainly the genetic continuity of the population, but the role of specific habits,
which concern diet and physical activity, and the environment appears to be
predominant.  
Some genes have been identified, called longevity genes, whose activity is
measurable and modifiable.
The longevity genes
The longevity genes Let’s take the case of Blue Zones, well defined geographical
areas with high percentages of centerians. Their key pillar is certainly the genetic
continuity of the population, but the role of specific habits, which concern diet
and physical activity, and the environment appears to be predominant. This is
because, as is now clear, our genome has the ability to “dialogue” and “adapt” to
the environmental context in which it operates. If this dialogue is properly
governed, the 9 hallmarks of ageing will be triggered much more gradually or will
not occur at all, leading to good health and good quality of life. And giving the
possibility to live the maximum of the individual own longevity reserve. Sirtuins
  activate under stressful conditions – such as nutrient shortages and cold
temperatures – or in the presence of threats, to reduce cellular reproduction
activity and concentrate all resources on survival. ‍ All organisms have sirtuin
genes. Among their most important functions is to self-activate in conditions of
metabolic stress – such as nutrient shortages and cold temperatures – or in the
presence of threats, to reduce cellular reproduction activity and concentrate all
resources on survival.
 Sirtuins are proteins expressed by SIRT genes that perform an enzymatic activity,
which means they stimulate chemical reactions essential for the body. Their
function has been ascertained by several studies, although there still seems to be
a lot to know about them. SIRTs in short:
• are proteins with enzymatic properties
• regulate the metabolic processes related to insulin resistance
• have a control over immunity
• have a fundamental role in epigenetics
• are involved in defences against cancer
 It has been known since the 1930’s that a moderate calorie restriction prolongs
life, and it has been later demonstrated that this is due to the action of sirtuins
. ‍ Today we know that lifestyle can influence the expression (i.e. “production”)
and activity of sirtuinsSirtuins are proteins expressed by SIRT genes that perform
an enzymatic activity, which means they stimulate chemical reactions essential for
the body. Their function has been ascertained by several studies, although there
still seems to be a lot to know about them. SIRTs in short:
• are proteins with enzymatic properties
• regulate the metabolic processes related to insulin resistance
• have a control over immunity
• have a fundamental role in epigenetics
• are involved in defences against cancer
, such as moderate fasting and calorie restriction. It has been known since the
1930’s that moderate calorie restriction prolongs life. In the early 2.000. it was
found that calory restriction acts via the induction of sirtuin activation. Another
moderate stress capable of modulating the expression of these proteins is non-
competitive physical activity. Not only that. Both what we eat and the time of the
day we eat (e.g. avoid certain foods before sleep) affect their activity. We have
also identified some active ingredients (molecules naturally present in the plant
world) that can stimulate   and increase their effectiveness. Monitoring
epigenetic aging, chrono-nutrition programs, nutritional supplementation with
active ingredients of natural origin, moderate physical activity
programs and neurocognitive training are the cornerstones of an effective
strategy to stimulate sirtuin activity and preserve our “longevity reserve”. And
they are the fundamental axes of SoLongevity’s research. SoLongevity
Research SoLongevity’s research leverages on the intervention on 5 of the 9
hallmarks of aging, through a medical program based on the principle of
“measuring and acting“, and the use of cutting-edge instruments of Precision
Medicine.
1. Precise measurement of epigenetic aging and biological age different from
chronological age. It is a measure of the body's ageing, based on the
effectiveness of the mechanisms that keep cells young and on markers of
the functionality of organs and apparatus.
2. Measurement of physiological parameters, focused on three dimensions:
 The immuno-metabolic dimension, i.e. the evaluation of metabolic
and inflammatory parameters.
 The neurocognitive dimension, i.e. the evaluation of cognitive
abilities to develop a path for their enhancement and/or recovery.
 The cardio-respiratory and muscle-skeletal dimensions, i.e. the
evaluation of the physical state to establish the optimal level of
motor activity.
3. Targeted and personalized intervention on the sirtuin system through three
strategies: nutrition, dietary supplementation based on active ingredients
of natural origin and physical activity.
If acting on only one of the 9 causes of aging can bring the whole system back into
balance, improving 5 of them can be even more effective in slowing down the
aging process. Our measurement systems enable us to monitor the impact of our
programs over time