Biochemistry of Hormones and Aging

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BIOCHEMISTRY OF HORMONES

Hormone
The word hormone is derived from a Greek word "Hormacin" which means to
"Excite". Hormones are strictly speaking stimulating substances and act as body
catalysts. The hormones catalyze and control diverse metabolic processes, despite
their verifying actions and different specificities depending on the target organ.
Hormone Secretion
Hormones in animals are often transported in the blood. Endocrine hormone
molecules are secreted (released) directly into the bloodstream. Exocrine
hormones (ecto hormones) are secreted directly into a duct, and from the duct,
they either flow into the bloodstream or they flow from cell to cell by diffusion.
Hormone secretion can be stimulated and inhibited by:
● Other hormones (stimulating or releasing hormones)
● Plasma concentrations of ions or nutrients
● Neurons and mental activity
● Environmental changes (eg. Change in light or temperature)
Effect of hormones
Hormones have the following effects on the body:
● Stimulation or inhibition of growth
● Mood swings
● Activation or inhibition of the immune system
● Regulation of metabolism
● Preparation of the body for fighting, fleeing, mating, and other activities
● Control of the reproductive cycle
● Preparation of the body for a new phase of life, such as puberty, parenting,
and menopause
● Hunger cravings
● Hormone may also regulate the production and release of other hormones.
● Hormone signals control the internal environment of the body through
homeostasis
Classification of Hormones
1. PEPTIDES AND PROTEINS
● Peptide and protein hormones are products of translation.
● Peptide hormones are synthesized in endoplasmic reticulum,
transferred to the Golgi and packaged into secretory vesicles for
export
● including hormones secreted by the anterior and posterior pituitary
gland, the pancreas (insulin and glucagon), the parathyroid gland
(parathyroid hormone)
2. AMINO ACID DERIVATIVES
There are two groups of hormones derived from the amino acid, tyrosine:
● hormones (ending in ‘-ine’) are derived from tyrosine and tryptophan and
include epinephrine and norepinephrine (produced by the adrenal medulla)
Two other amino acids are used for the synthesis of hormones:
● Tryptophan is the precursor to serotonin and the pineal hormone melatonin.
● Glutamic acid is converted to histamine
3. STEROIDS
● Steroids are lipids and, more specifically, derivatives of cholesterol.
● (ending in ‘-ol’ or ‘-one’) include estradiol, testosterone, aldosterone, and
cortisol.
● Steroids secreted by the adrenal cortex (cortisol and aldosterone), the
ovaries (estrogen and progesterone), the testes (testosterone), and the
placenta (estrogen and progesterone).
Final effects of hormones action
1. Change the permeability of cell membrane.
2. Accelerate the penetration of substrates, enzymes, and coenzymes into the
cell and out of cell.
3. Acting on the allosteric centers, affect the activity of enzymes (Hormones
penetrating membranes).
4. Affect the activity of enzymes through the messengers (cAMP). (Hormones
that cannot penetrate the membrane).
5. Act on the genetic apparatus of the cell(nucleus, DNA) and promote the
synthesis of enzymes (Steroid and thyroid hormones)
FACTORS REGULATING HORMONE ACTIONS
1. Action of a hormone at a target organ is regulated by four factors:
2. Rate of synthesis and secretion: The hormone is stored in the endocrine
glands.
3. In some cases, specific transport systems in plasma.
4. Hormone-specific receptors in target cell membranes which differ from
tissue to tissue.
5. Ultimate degradation of the hormones usually by the liver or kidneys
Endocrine and exocrine glands
● Unlike exocrine glands(sweat, salivary), endocrine glands secrete their
respective substances directly into the bloodstream rather than through a
duct.
● These endocrine glands belong to the body’s control system and they
produce hormones which help to regulate the functions of cells and tissues.
● Some glands are specific to either male (testes) or female (ovaries)
Endocrine Glands

Gland Hormones Effect of hormones


produced

Pineal gland Melatonin Affects reproductive development and daily


physiologic cycles

Pituitary Growth Controls growth of bones and muscles


gland hormone(GH)
Increases reabsorption of water in kidneys
Antidiuretic
hormone Controls development of ovaries and testes

Gonadotrophins

Thyroid gland Thyroxine Controls rate of metabolism and rate that glucose
is used up in respiration and promote growth

Adrenal gland Adrenaline Prepares the body for emergencies, increases


heart rate and depth of breathing, raises blood
sugar level so more glucose is available for
respiration, diverts blood from gut to limbs

Pancreas Insulin Converts excess glucose into glycogen in liver

Glucagon Converts glycogen back into glucose in liver

Ovaries Oestrogen Controls ovulation and secondary sexual


characteristics

Progesterone
Prepares the uterus lining for receiving an
embryo

Testes Testosterone Controls sperm production and secondary sexual


characteristics

thymus Thymoxine Promotes production and maturation of white


blood cells

Exocrine glands
1. GLUCAGON (PROTEIN HORMONE)
Glucagon is a hormone produced by
α-cells of islets of Langerhans of
pancreas and is an important hormone
involved in:
*Rapid mobilization of hepatic glycogen
to give glucose by
glucogenolysis/glycogenolysis
*To a lesser extent FA from adipose
tissue. Thus, it act as a hormone required
to mobilise metabolic substrates from
storage depots.
CHEMISTRY:
Glucagon has been purified and
crystallized from pancreatic extracts and
also the hormone has been synthesized.
It is a polypeptide containing 29 amino
acids
2.ESTROGEN (STEROID HORMONE)
Estrogen are hormones capable of
producing certain biological effects.
They include:
● Growth of female genetic organs
● The appearance of female secondary sex characteristics
● Growth of the mammary duct system and numerous other phenomena
which vary somewhat in different species.
CHEMISTRY:
The naturally occurring estrogens in humans are:
● β-Estradiol
● Estrone
● Estriol
3. EPINEPHRINE & NOREPINEPHRINE (AMINO ACID DERIVATIVE)
● They are the hormones secreted from adrenal gland from adrenal medulla.
● They help in fight and flight responses.
CHEMISTRY:
● The naturally occurring forms are levorotatory.
● They don’t have – COOH (CARBOXYLIC) group.
● They act as neurotransmitters.
● They are stored in the form of granules.

SIMILARITIES & DISSIMILARITIES OF HORMONES &


ENZYMES SIMILARITIES
SIMILARITIES:
● Both act as body catalysts.
● Both are required only in small quantities.
● Both are not used up during the reaction
DISSIMILARITIES:
● Hormones are produced in an organ other than that in which they ultimately
perform their action.
● They are secreted in blood prior to use.
● Structurally they are not only proteins. Few hormones are protein in nature,
few are small peptides. Some are derived from amino acids while some are
steroids in nature
IMPORTANCE OF HORMONES
● simulation of growth,
● control of cell’s life span, control of immune system,
● metabolism regulation,
● control of phases of life,
● self-preservation reactions, sexual functions, reproductive cycle.
● Hormones are chemical messengers in the body which control certain
processes in the body, such as reproduction and homeostasis

LINKS:
https://www.youtube.com/watch?v=MHOpVy8VcXk&t=111s
https://www.youtube.com/watch?v=MHOpVy8VcXk&t=111s
https://www.youtube.com/watch?v=MHOpVy

BIOCHEMISTRY OF AGING
Aging
Gradual change in an organism that leads to increased risk of weakness, disease,
and death over the entire adult life span of any living thing. There is a decline in
biological functions and in ability to adapt to metabolic stress.
Most definitions of aging indicate that it is a progressive process associated with
declines in structure and function, impaired maintenance and repair systems,
increased susceptibility to disease and death and reduced reproductive capacity
Changes in organs include:
● reduced immunity,
● loss of muscle strength,
● decline in memory and cognition,
● loss of color in the hair
● elasticity in the skin
Concepts of aging:
● Chronologic aging
● biological aging
● psychologic aging
● social aging
● cognitive aging
Chronologic aging
● Chronological age refers to the actual amount of time a person has been
alive
● In other words, the number of days, months or years a person has been alive
Biologic aging
● Senescence or biological aging is the gradual deterioration of function
characteristics
● Biological aging refers to the physical changes that "slow us down" as human
get into middle and older years
● For Example: arteries might clog up, or problems with lungs might make it
more difficult for us to breathe
● This aging is also known as physiologic aging
Physchologic aging
● phychological aging refer to the psychological changes, including those
involving mental functioning and personality, that occur as human age
● chronological age is not always the same thing as biological or psychological
age
● some people who are 65, can look and act much younger than some who are
50
● psychological aging may be seen as continous struggle for identity (eg. for a
sense of coherence and meaing in thoughts, feeling and action)
● success depends on a lucy synchronization of changes through kife in
different parts of the personal self
Social aging
● social aging refers to changes in a person's roles and relationships, both
within their networks of relatives and friends and in formal organizations
such as the workplace and houses of worship
● social aging differ from one individual to another
● it is also profoundly influenced by the perception of aging that is part of a
society's culture
● if a society views aging positvely, the social aging experienced by
individuals in that society will be more positoive and enjoyable than in
society that views aging negatively

Cognitive Aging
● Cognitive aging is the decline in cognitive processing that occurs as people
get older. Age-related impairments in reasoning, memory and processing
speed can arise during adulthood and progress into the elder years
● cognitive aging is concerned with the basic processes of learning and
memory as well as with the complex higher-order processes of language
intellectual competence or executive functioning
● the concept of cognitive aging, a term that describes a process of gradual,
longitudinal changes in cognitive functions that accompany the aging
process
Theories of aging
● Each theory of aging attempts to provide a framework in which to
understand aging from different perspectives
● Each theory is useful to the clinician because a framework and insight into
differences among elderly patients are provided
The theories of aging are classified into:
● Biological theories
● Psychosocial theories
● Developmental theories
Biologic Theories
● Biologic theories of aging attempt to explain why the physical changes of
aging occur
● Researcher try to identify which biologic factor have the greatest influence
on longevity
○ The programmed theory/ Biological clock theory
○ The run out of program theory
○ Gene theory
○ Molecular theory
○ cellular theories
The programmed theory/biological clock theory
● proposes that every person has a "biologic clock" that starts clicking at the
time of conception
● In this theory, each individual has a genetic program specificying an
unknown but predetermined number of cell divisions
● As the program plays out, the person experiences predictable changes such
as atrophy of the thymus, menopause, skin changes and graying of the hair
● Aging has a biological timetable or internal biological clock
The Run out of program theory
● Every person has a limited amount of genetic material that will run out over
time
● All events are specifically programmed into genome and are sequentially
activated
● After maturation of genes have been activated there are no more programs to
be played and as cels afe there may be chance of inactivation of genes that
cannot be turned on
Gene Theory
● The gene theory proposes the existence of one or more harmful genes that
activate overtime, resulting in the typical changes seen with aging and
limiting lifespan of the individual
● Organism failure occurs in later life because f the presence of imperfect
genes activated over lengthy periods of time
● Two genes, one supports growth and vigor, and the other supports
senescence and deterioration

Molecular theories
● The aging is controlled by genetic materials that are encoded to
predetermine both growth and decline
○ The error theory
○ The somatic mutation theory
The error theory
● The error theory proposes that errors in ribonucleic acid protein synthesis
cause errors to occur in cells in the body, resulting in a progressive decline
in biologic function
● Error theory aging is a result of internal or external assaults that damage
cells or organs so they can no longer function properly
The somatic mutation theory
● The somatic mutation theory proposes that aging result fom
deoxyribunucleic acid (DNA) damage caused by exposure to chemicals or
radiation and this damage causes chromosomal abnormalities that lead to
disease or loss of function later in life
● Exposure to x ray radiation and or chemicals induces chromosomal
abnormalities
Cellular theories
● The cellular theories propose that aging is a process that occurs because of
cell damage
● When enough cells are damaged, overall functioning of the body is
decreased
○ The free radical theory
○ The crosslink or connective tissue theory
○ Clinker theory
○ The wear and tear theory
The free radical theory
● Denham Harman 1956
● The term free radical describes any molecule that has a free electron, adn
this property maeks it react with healthy molecules in a destructive way
● Free radical molecule creates an extra negative charge
● This unbalanced energy makes the free radical binds itself to another
balanced molecule as it tries to steal electrons
● Balanced molecule becomes unbalanced and thus a free radical itself
● Diet, lifestyle, drugs (eg. tobacco and alcohol) and radiation
Theory crosslink or connective tissue theory/Glycosylation theory of aging
● Cell molecules from DNA and connective tissue interact with free radicals to
casue bonds that decrese the ability of tisue to replace itself
● The result in the skin changes typically attributed to aging such as drynes,
wrinkles, and loss of elasticity
● Fibrous tendons, loosening teeth, diminished elasticity of arterial walls and
decreased efficiency of lungs and GI tract
● It is binding of glucose (simple sugars) to protein, (a process that occurs
under the presence of oxygen) that causes various problems
● Senile cataract and the appearance of tough, leathery and yellow skin
The clinker theory
● The clinker theroy combines the somatic mutation, free radical and cross
link theories to suggests that chemicals produced by metabolism
accumulate in normal cells and cause damage to body organs such as the
muscles, heart, nerves and brain
The wear and tear theory
● Body is similar to a machine, which loses function when its pars wear out
● As people age, their cells, tissue and organs are damaged by internal or
external stressors
● Good health maintenance practices will reduce the rate of wear and tear,
resulting in longer and better body function

The Neuroendocrine theory


● Prof. Vladimir Diman and Ward Dean
● This theory elaborates on wear and tear by focusing on the neuroendocrine
system
● This system is a complicated network of biochemicals that govern the
release of hormones which are altered by by hypothalamus
● The hypothalamus controls various chain-reactions to instruct other organs
and glands to release their hormone etc. The hypothalamus also responds to
the body hormone levels as a guide to overall hormonal activity.
Accordingly, as ages, the secretion of many hormones declines and their
effectiveness is also reduced due to the receptors downgrading
Immunologic theory
● The immunologic theory proposes that aging is a function of changes in the
immune system
● The immune system weakens over time, making an aging person more
susceptible to disease, increase in autoimmune disease and allergies
● Over time, cells involved in immune function are less self regulatory,
resulting in cells being misidentified as foreign material adn being attacked
by the immune system's own defenses. Eg: rheumatoid arthritis (RA) and
lupus
The mitochondrial decline theory
● The power-producing organelles
● Their primary job is to create Adenosine Triphosphate (ATP) and they do so
in the various energy cycles that involve nutrients such as
Acetyl-L-CArnitine, CoQ10 (Idebenone), NADH and some B vitamins, etc.
● Enhancement and protection of the mitochondria is an essential part of
preventing and slowing aging
The membrane theory of aging
● Professor Imre Zs
● It is the age-related changes of the cells ability to transfer chemicals, heat
and electrical processes that impair it.
● As older the cell membrane becomes less lipid (less watery and more solid).
This impedes its efficiency to conduct normal function and in particular,
there is toxic accumulation
Gerontology and Geriatrics
● Gerontology is concerned with the changes that occur between maturity
and death along with factors that influence these changes.
● Geriatrics focuses on health care of elderly people and promote health by
preventing and treating diseases and disabilities in older adults.
Factors of Aging
● mitochondrial damage
● free radicals
● telomeres
● apoptosis and necrosis diseases
● other effects
Mitochondria: main unit of chemical power supply
● During the synthesis of macroergical biomolecules(high energy releasing
potentials e.g. ATP) free radicals are being produced as the by-product.
● Free radicals released in large quantities cause intercellular oxidative stress
(e.g. oxidative damage of mitochondria)
● Damaging mitochondria and cause early apoptosis
Free radical
A molecule that contains one or more unpaired electrons &is capable of
independent existence.
Eg: Superoxide H2O2, hydroperoxy radical (HOO+2 ), lipid peroxiradical (ROO),
Nitric oxide (NO)

Factors of aging
● Harmful effect of free radicals
○ Because of their reactive nature, free radicals can provoke
inflammation or altered cellular function through
■ Lipid peroxidation
■ Protein modification
■ DNA modification
Evidence for the free radical theory of aging includes proven damage to DNA,
lipids. and protein; noted increases in abnormal mitochondria with age; proven
acceleration of age with ionizing radiation; and superoxide dismutase in trisomy

Factors of Aging
Lipid peroxidation product:
● React with amino acid mainly CYS, HIS,LYS to modify protein structure &
function.
● Can crosslink lipid in cell membrane interrupting structure & fluidity
Protein modification
● Proteins are major targets of free radical attack because of their high
abundance & responsible for most of functional processes.
● – Free radical causes oxidation & modification of certain amino acids (met,
cys,His,try)
● – ROS may damage protein by fragmentation
● – net result is loss of biological activity of proteins
DNA modification :
● Free radical induced DNA damage includes
● strand break.
● DNA protein crosslink.
● large range of base & sugar modification
Telomeres
● Repetitive DNA sequences at the ends of all human chromosomes
● aging cells have shorter telomeres
● length differs between species
● in humans 8-14kb long
● Telomeres are thought to be the "clock" that regulates how many times an
individual cell can divide.
● Telomeric sequences shorten each time the DNA replicates.
● Once the telomere shrinks to a certain level, the cell can no longer divide. Its
metabolism slows down, it ages, and dies
Apoptosis and Necrosis
There are two ways that a cell can die:
● Necrosis occurs when a cell is damaged by an external force, such as poison,
a bodily injury, an infection or getting cut off from the blood supply (which
might occur during a heart attack or stroke).
● When cells die from necrosis, it's a rather messy affair. The death causes
inflammation that can cause further distress or injury within the body
Apoptosis or programmed cell death
● When a cell is compelled to commit suicide proteins called caspases go into
action.
● They break down the cellular components needed for survival,
● Production of enzymes known as DNases, which destroy the DNA in the
nucleus of the cell
Apoptosis Process
1. Cells damaged, stresses or triggered by body signals, begin apoptosis
2. The cell begins to shrink and forms blebs. Proteins are activated to break
down cellular components
3. Enzymes break down the nucleus and the cell emits signals to attract
macrophages
Diseases: progeria(Hutchinson-Gilford syndrome)
Werner Syndrome (adult progeria)
Hallermann-Streiff-François syndrome
Other effects:
● Stress effects
● Octopus suicide
○ The octopus suicide mechanism involves behaviors where females
stop eating and die of starvation
Anti-aging agents:
● Aspirin
● Diet-Caloric restriction
● Exercise
● Lauging out louder
● Drugs
○ Resveratrol, a constituent of red wine and grape skins has been found
to extend life span
○ Rapamycin, spermidine, metformin
Non-aging species:
● Rougheye Rockfish-205 years
● Lake sturgeon-152 years
● Aldabra Tortise-152 years
● Koi-226 years
● Bowhead whale-211 years

LINKS:
Biochemical aspects of Aging
https://www.youtube.com/watch?v=7dYw9T08VWM
Theories of Aging / Why do we Age / Aging / Classification of Theory of Aging
https://www.youtube.com/watch?v=KSR_eVubGdA

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