This document discusses aging and theories of aging. It defines key terms like gerontology and geriatrics. The major theories of aging discussed include the genetic/DNA theory involving telomere shortening, the neuroendocrine theory involving hormonal changes with age, the free radical theory of cellular damage from oxidative stress, and the mitochondrial decline theory of reduced energy production in cells. The document also outlines common age-related changes that occur in major organ systems like the cardiovascular, respiratory and nervous systems. Diet, exercise and minimizing oxidative damage are presented as potential ways to modulate the aging process.

1. Aging
Dr. Aamir Magzoub
MBBS, MSc, PhD

2. Objectives:
 Definitions: aging, gerontology,
geriatrics.
 Aging Theories.
 Age-related changes.
 Modulating the process of aging.

3. Definitions
 The process of growing old, following
physical maturity, accompanied by
deterioration in the vitality or the biological
efficiency (appearance, behavior,
experience, etc.),
 The biological age of the person is not
identical with his chronological age.

4. Definitions
 Gerontology is the scientific study of
the aging process.
 Geriatric medicine or Geriatrics is the
branch of medicine concerned with the
medical problems of aged (elderly)
people (increased % of elderly).
 Knowledge of changes due to aging
process is essential for treating
abnormalities.

5. Theories of Aging

6. Theories of Aging
(most important)
1. Genetic (DNA) Theory.
2. The Neuroendocrine Theory.
3. The Free Radical Theory.
4. The Membrane Theory (cell wastes accumulation).
5. The Hayflick Limit Theory.
6. The Mitochondrial Decline Theory.
7. The Cross-Linking Theory (Glycosylation Theory).

7. 1. Genetic (DNA) Theory
 It focuses on the encoded program
within our DNA, i.e. programmed aging.
 All body functions are preplanned to
function and decline at a certain age
(genetic code).
 DNA is easily oxidized and damaged:
– Diet, lifestyle, toxins, pollution and radiation
(i.e. accelerate or slow DNA damage).

8. 1. Genetic (DNA) Theory
Telomere and aging:
 Telomere: A region of repetitive
DNA sequences at each end of
the chromosomes.
 They shorten every time as cells
divide.
 This shortening of telomeres is
believed to lead to cellular
dysfunction due to the inability
of the cell to duplicate itself
correctly. (dysfunction aging
and cell death). – Hayflick limit.

9. 1. Genetic (DNA) Theory
Telomere and aging:
 Telomeres can be
repaired by the
introduction of the
relevant substance
(genetic repair).
 Telomerase enzyme
appears to repair and
replace telomeres
(help re-regulate the
clock).

10.  The hypothalamus is the neural controller of
various endocrine glands and responds to the
body hormone levels as a guide to the overall
hormonal activity.
 As we grow older:
– Decrements in brain neurons & the hypothalamus loses
its precise regulatory ability.
– Less sensitivity of the individual hormones’ receptors.
 Therefore, the secretion and effectiveness of
many hormones become disturbed (e.g.
hormones controlling cell metabolism).
2. The Neuroendocrine Theory

11.  The hormone cortisol may alter the
hypothalamic regulatory function.
 High cortisol causes hypothalamic
damage (becomes less sensitive).
 Cortisol is produced from the adrenal
glands in response to stress.
 Impact of stress on aging?
2. The Neuroendocrine Theory

13.  The term free radical describes any
molecule that has a free electron (extra
negative charge), e.g. hydroxyl radical
(OH-) & superoxide radical (O2
-).
 This property makes it to react with
healthy molecules in a destructive way.
 Free radicals attack the structure of cell
membranes, disturb DNA, RNA and
impede vital chemical reactions.
3. The Free Radical Theory

14.  Diet, lifestyle, drugs, tobacco, alcohol,
radiation, etc., are all accelerators of free
radical production within the body.
 There is also natural production of free radicals
from the mitochondria by the simple process of
eating, drinking and breathing (oxidation).
 Anti-oxidants (free radical scavengers) bind to
particular free radicals and stabilize them.
 Example of antioxidants: beta carotene,
vitamins C & E (fresh fruits & vegetables)
3. The Free Radical Theory

15.  As we grow older, the cell membrane will
have less lipid (less soluble and more solid).
 This decreases membrane exchange and
hence accumulation of waste (toxic) products
which impede normal cell function.
 Lipofuscin is an example of cell accumulated
products and deposits are seen in the brain,
heart, and skin of elderly people.
– Skin age-pigments are composed of lipofuscin.
– Alzheimer patients have higher lipofuscin deposits.
4. Membrane Theory
(cell wastes accumulation).

16.  This Theory suggests that the human cell is
limited in the number of times it can divide,
after which it simply stops dividing (and
hence die – diminished telomere DNA
damage).
 Nutrition has an impact on cell division:
– Overfed cells divide much faster than
underfed cells.
– Calorie restriction in animals significantly
increases their life-span.
5. The Hayflick Limit Theory

17. 5. The Hayflick Limit Theory:
Telomere Effect

18.  Mitochondria are the power (ATP) producing
organelles found in every cell of every organ.
 Under normal conditions, the mitochondria
continuously subject themselves to a lot of free
radical damage. They also lack most of the
defenses found in other parts of the body.
 So, as we age, the mitochondria become less
efficient and fewer in number; accordingly,
ATP production declines.
 Organs fail to form energy needed for repair,
secretion, absorption, etc. Antioxidants?
6. The Mitochondrial Decline
Theory

19.  Binding of glucose to protein (in the presence of
oxygen) is the cause of various problems –
(non-enzymatic glycosylation).
 Once Glucose binding occurs, the proteins form
cross-linking & become unable to perform their
functions . Example of cross-linking disorders:
– Senile cataract and senile skin (tough, leathery)
– Cardiac enlargement and hardening of collagen
(increased susceptibility of cardiac arrest)
– Renal disorders (glycosylation of filtration memb.)
– Sugars binding to DNA ( malformed cells & cancer)
7. The Cross-Linking Theory
(Glycosylation Theory).

20. Age-related changes in
different organ systems

21. Age-related changes in
different organ systems
 The decline of each organ system
appears to occur independently of
changes in other organ systems and is
influenced by:
– Diet.
– Environment and personal habits (lifestyle)
– Genetic factors.
 What are these changes?

22.  Decreased No of functioning cells.
 Decreased lean tissue mass.
 High fat content decreased total
body water and more susceptibility to
dehydration.
 Exercise stabilizes the lean tissue and
consumes fat.
1- General Cell number &
body built

23. 2- Cardiovascular system
 Atrophy or slight enlargement of left
ventricle.
 Calcification of the heart valves.
 Loss of elasticity in artery walls
(arteriosclerosis) – increased Bp & IHD.
 Decreased cardiac output & HRMax
 Less sensitivity to baroreceptors (postural
hypotension) – must sit before standing.
 Atrial fibrillation (ECG changes)

24.  Atrophy of the rib cage muscles, which
reduces the ability to breathe deeply.
 The airways and lung tissue become
less elastic with reduced activity of cilia.
 Reduced No of functioning alveoli.
 Increased residual volume.
 Decreased elasticity & lung capacity.
 Higher risk of respiratory infections.
3- Respiratory system

25.  Generalized atrophy of all muscles.
accompanied by a replacement of some
muscle tissue by fat deposits loss of muscle
tone and strength.
 Calcium is lost and bones become less dense:
– Osteoporosis and a reduction of weight
bearing capacity ( pathological fractures)
– Thinning of the vertebrae also results in a
reduction in height and postural changes.
 Joints also undergo changes (chronic arthritis)
4- Musculoskeletal system

26.  Diminished mastication efficiency (teeth problems)
 Difficulty in swallowing (dysphagia) – elderly age
 Reduction in the production of hydrochloric acid,
digestive enzymes and saliva.
– Impaired digestion and absorption of foods.
– Vitamin deficiencies (B12) and anemia
 Decreased liver weight with normal LFT, but
precaution with slowly metabolized drugs, e.g.
diazepam.
 Decreased colonic motility (constipation –
extremely old persons)
5- Gastrointestinal (GIT)

27.  1. Brain atrophy and neuronal loss
– By the age of 70 years, there may be
45% cell loss in cerebral cortex, and
25% loss in cerebellum.
 2. Degenerative changes:
 Senile parkinsonism (substantia nigra).
 Dementia (hippocampus & memory
retaining circuits)
 3. Sleep changes.
6- The central nervous
system

28.  I. Changes in vision:
 1. There is loss of accommodation which
makes reading and close work difficult
(presbyopia – 40+ years).
 2. Senile cataract (elderly).
 3. Decreased perception of colors.
 II. Changes in hearing:
 Presbycusis: gradual hearing loss specially
high frequency sounds (decreased
sensitivity) – 1/3rd of 75+ years.
7- The special senses

29.  II. Changes in taste & smell:
 Impaired sensations of taste and smell.
 Reduction in the total number of taste
buds (80+ years).
7- The special senses cont

30.  A gradual decrease in the volume and weight of
the kidneys.
 Renal size is about 70% in 90+ years.
 A decline in the total number of glomeruli per
kidney from about 1,000,000 below the age of
40 to about 700,000 by age 65 yrs.
 Age-related decrease in the creatinine clearance
& drug excretion – precaution with some drugs.
 Decreased bladder capacity (>65); incontinence
8- The Renal system

31.  Sexual desire and performance may
continue well although frequency &
excitements may diminish (80+ years).
 In women include atrophy of the ovarian,
vaginal and uterine tissues with
decreased production of vaginal fluids
(dyspareunia).
 In men, sperm production is decreased
and prostate enlarges (BPH 90% - 80+).
9- The Reproductive
system

32.  A progressive deterioration in the
number and the function of insulin-
producing beta cells (senile DM).
 Decreased thyroid hormones ( BMR).
 Estrogen and progesterone are
decreased after menopause (females)
and testosterone (70+ males) with high
FSH & LH ( -ve feedback)
10- Endocrine system &
metabolism

33.  After age 25, there is approximately
1% decrease per year in the
metabolic rate.
 There is a decrease in the overall
metabolism of drugs.
10- Endocrine system &
metabolism cont.

34.  Skin loses underlying fat layers, causing
wrinkles and reduced elasticity.
– Increased susceptibility to cold, bruising
and bedsores (managing bedridden pts)
 Skin develops “age spots” – lipofuscin.
 The skin becomes less sensitive to
sensations including heat, cold and injury.
 The hair gradually loses its pigmentation
and turns gray - white.
11- Skin & hair

35. Modulating the process of
aging
 Aging process has proved to be an
inevitable process.
 The only measures that have shown
some progress in modulating this
process are: caloric restriction and
exercise.