Physiology of

Ageing
Ageing is a natural process

• Ageing can be defined as time-related deterioration of

physiological functions necessary for survival and fertility

• Science of ageing is often referred to as gerontology

• Scientists studying science of ageing are known as gerontologists

• Branch of medicine dealing with the problems of ageing is called

geriatric medicine
 Age-related Changes in Different Organ Systems

I. CARDIOVASCULAR CHANGES
Changes in heart:
A. Myocardium may show following changes:
1. Deposition of yellow brown lipofuscin pigment
2. Degenerative changes in the myofibrils and mitochondria
3. Fibrotic lesions and sometimes amyloid deposits
4. Capillary density may be decreased
B. Valves show thickening and structural changes:
1. Aortic valve somewhat stenotic
2. Mitral valve slightly incompetent
C. Functional changes in heart of elderly include:
3. Heart rate in resting conditions is unchanged. But maximum
heart rate during exercise ↓
4. Maximum cardiac output in response to exercise is ↓ at rate of
1% per year after age of 40 years
D. Sinoatrial (SA) node automaticity and baroreceptor sensitivity
↓ with age
E. ECG does not show any significant change with age
Changes in blood vessels and blood pressure:
1. Blood vessels :
Show a gradual decrease in number of elastic fibres
Progressive change in characteristics of elastic tissue
↓ in distensibility of blood vessels due to deposition of calcium
salts in elastic and muscular type of arteries & deposition of
more collagen fibres
2. Blood pressure:
• Systolic blood pressure is raised because of loss of elasticity in
aorta and its major branches
• Little change in diastolic blood pressure
• Widening of pulse pressure

3. Blood flow:
• ↓ in blood flow to various organs, such as heart, brain and
especially kidney
II. CHANGES IN RESPIRATORY SYSTEM
A. Structural changes in lungs:
• Alveoli become flatter and shallow
• Alveolar ducts enlarge
• Number of alveoli declines gradually due to progressive loss of
interalveolar septa
B. Pulmonary compliance:
• ↑ due to decrease in elasticity of the lungs
C. Compliance of thoracic cage and mobility of the ribs:
• ↓due to calcification of costal cartilages
D. Pulmonary blood vessels: show age-related increase in wall
thickness
E. Functional changes :
• Functional residual capacity of the lungs is ↑ by 50%
• Residual volume is ↑ by 100%
• Vital capacity, FEV1, MVV and diffusion capacity for O2 -
significantly ↓
• Respiratory response to hypoxia and hypercapnia becomes
sluggish
• Airways become more susceptible to collapse
• Arterial pCO2 and pO2: Arterial pCO2 is not changed, but
arterial pO2 is ↓ by 10–15%
• Impairment of bronchiolar escalator function
III. GASTROINTESTINAL TRACT CHANGES
1. Diminution of masticatory efficiency occurs due to teeth problems
2. Difficulty in swallowing (dysphagia) may occur
3. Reduction in gastric secretion leading to achlorhydria is seen in 25%
of individuals above 60 years of age
4. Age-related changes in small intestine include ↓ in villus height & ↓
in lactase activity in brush border  ↓ absorptive capacity
5. Colon motility may be ↓ constipation
6. Changes in liver:
• ↓ in number but ↑ in size of hepatocytes
• ↑ in fibrous tissue
• Synthetic functions of liver are ↓
IV. RENAL AND GENITOURINARY CHANGES
A. Kidneys :
• Show progressive reduction in weight
• Functional renal changes :
1. ↓ glomerular filtration rate because of 30–40% ↓ in number of renal glomeruli
2. ↓ in tubular function, both secretory and absorptive activity, leads to ↓ urinary
concentration and dilution abilities
3. Renal function becomes borderline
B. Prostate :
• Enlargement in elderly males is a quite frequent cause of ↑ residual urine volume
C. Vaginal/urethral mucosal atrophy occurring in elderly females leads to
dyspareunia and bacteriuria
V. CHANGES IN ENDOCRINAL SYSTEM
1. Thyroid hormone secretion is decreased
2. Impaired glucose homeostasis is frequently seen in old age.
due to diminished sensitivity of tissues to insulin
3. Reproductive hormones show most consistent age related changes
In females- plasma levels of oestrogen and progesterone are ↓ after
menopause
In males, testosterone levels are decreased around the age of 70
years
4. Anterior pituitary hormones secretion is not decreased
FSH and LH levels in females are rather ↑ due to negative
feedback effect
Gonadotropin levels in males are ↑ because of negative
feedback effect of lowered testosterone levels
5. ADH, renin and aldosterone levels are decreased in old age
6. Vitamin D absorption and activation is decreased with age and
contribute to osteoporosis
VI. CHANGES IN BLOOD AND IMMUNE MECHANISMS
1. Blood volume and blood cells: are not significantly affected
2. Haemopoietic marrow reserve is gradually ↓
3. Anaemia in elderly usually occurs due to ↓ of Iron and Vitamin
B12
4. Senile purpura occurs due to defect in capillary endothelium
5. Raised ESR is related to ↑ plasma fibrinogen levels
6. Immunological function is markedly depressed: Both cell
mediated immunity and humoral immunity are declined
VII. CHANGES IN MUSCULOSKELETAL SYSTEM

1. Muscular power  progressively ↓ with ageing due to loss of

muscle fibres (↓lean body mass)

2. Muscle twitch reveals a prolongation of latency, contraction

period and relaxation period

3. Osteoarthritis – age related degenerative changes in joints

4. Osteoporosis - age related ↓ in bone density is a
characteristic feature of ageing
5. Changes in stature and posture
• occur mainly due to changes in vertebral column
• Initially, there occurs thinning of intervertebral disc
• Osteoporotic changes cause a decrease in height of individual
vertebra
• Kyphosis and slight flexion at hip and knee
VIII. CHANGES IN SKIN AND HAIR
1. Wrinkling of skin: due to ↓ elasticity, ↑ thinning of
epidermis and dermis and ↓ subcutaneous fat
2. Greying of hair: due to loss of melanin pigment
3. Baldness in males
4. Loss of axillary and pubic hair in females occurs due to ↓
levels of adrenal androgens
5. ↑ in facial hair growth may occur in females: due to
unopposed action of residual adrenal androgens
6. Sweat glands ↓ in size and number
IX. CHANGES IN CENTRAL NERVOUS SYSTEM
1. Brain atrophy and neuronal loss
2. Degenerative changes may occur in substantia nigra and
lentiform nucleus
3. Other histological changes include accumulation of
lipofuscin granules, loss of synapses and gradual loss of
dendrites
4. Cerebral blood flow is decreased and ↓ in oxygen
utilization
5. Reflexes tend to sluggish or even absent
6. Functions of neurotransmitters are impaired:
• cholinergic deficit has been in Alzheimer’s disease
• dopaminergic deficit in Parkinson’s disease
• ↓ in catecholamine synthesis may be responsible for
depression
7. Sleep changes occur in the form of decrease in stage 3 & 4
of non-REM sleep
X. CHANGES IN AUTONOMIC NERVOUS SYSTEM
1. Impaired temperature regulation
2. Postural hypotension: due to partial failure of baroreceptor mechanism

XI. CHANGES IN SPECIAL SENSES

(i) Age-related ocular changes:
• Presbyopia
• Age-related cataract or senile cataract
• Age-related corneal degeneration: manifests as ring-shaped whitish opacity
near limbus - called Arcus Senilis
• Age-related macular degeneration (ARMD)
• Dry eye – due to decrease in tear secretion
(ii) Age-related changes in ears:
• Presbyacusia – age related impairment of hearing especially for
higher frequencies
- occurring due to degenerative changes in the organ of Corti,
ganglion cells as well as of temporal cortex
• Otosclerosis - characterized by age-related ↓ in motility of middle
ear ossicles
• Impairment of postural reflexes:
- due to age related degenerative changes in hair cells of crista
ampullaris & ↓ endolymph production
(iii) Age-related changes in taste and smell:
1. Impairment in taste sensation - attributed to ↓ in number of
taste buds
2. Impairment in smell sensation - attributed to ↓ smell receptors
and partly to loss of neurons in cerebral cortical centres
 Theories of Ageing
2 main groups of theories:
Genetic theories of ageing
Random damage theories

Genetic theories of ageing : most accepted 2 theories in this

group-
1. Programmed senescence theory
2. Mutation theory
1. Programmed senescence theory:

States: Ageing is the result of segmental switching on and off

of certain genes; with senescence being defined as time when
age-associated deficits are manifested
2. Mutation theory:

• Suggests that since animals usually succumb to natural forces

long before reaching their maximal life span, ageing might
reflect mutations that impair long-term survival

• These mutations would accumulate in genome because there

is no selection pressure to delete them
The ‘random damage’ theories of ageing
Includes :
1. Free radical theory
2. Cell replication theory
3. Cross-linking theory
1. Free radical theory:

• Oxidation reactions in cells are associated with formation of free

radicals such as superoxide and hydroxyl radicals

• For free radical scavenging antioxidant mechanisms exist in

body in form of glutathione, vitamin E, vitamin A and vitamin C
• Free radicals induced damages:

- damage vital macromolecules, such as DNA and proteins

- cause peroxidation of lipids in membranes around cells and

organelles

• Though effects of antioxidants are highly recommended but

no proof is available to verify its effect
2. Cell replication theory:
• Suggests that ageing may represent a stage of life when replication
of cell ceases .i.e. when repair is not capable to cope up with
damage
• Cell replication has also been linked to length of telomeric DNA
• With each cell division, roughly 50 of the total 2000 base pairs of
telomere are lost
• Telomeric shortening might thus result in loss of gene
accessibility, which is caused by metabolism

• Together with cytoplasmic factors telomeric shortening could

also limit cell’s ability to divide and thereby replace cells loss
to apoptosis
3. Cross-linking theory:
States - accumulation of cross-linked proteins damages cells
and tissues
Slowing down bodily processes and results in ageing
Crosslinks, termed advanced glycosylation end products
(AGEs) seem to toughen tissues and may cause some of
deterioration associated with ageing
AGEs have been linked to stiffening connective tissue
(collagen), hardened arteries, clouded eyes, loss of nerve
function and less efficient kidneys
 Modulating the Process Of Ageing
Measures that have shown some progress in modulating ageing are:
Calorie restriction & Exercise
Calorie restriction:
• To date - only intervention known to delay ageing and prolong life
span  calorie restriction (which has been proved in experimental
animals)
• Exact mechanism not known
Exercise:
• Improves work capacity as assessed from maximum oxygen
uptake
• Also improves cardiac performance and ↓ musculoskeletal
disability
• Prevent age-related decline in resting metabolic rate
Thank
You