The document discusses the physiology of aging, outlining concepts, theories, and the impact of aging on human physiological systems. It emphasizes the role of genetics, environmental factors, and free radicals in aging, along with various aging theories such as genetic and random damage theories. Additionally, it highlights the physiological changes that occur with aging, the importance of diet and exercise in influencing aging processes, and the challenges associated with age-related diseases.

1. Physiology of ageing – GERIATRIC PHYSIOLOGY
Dr. Sanjeev Shrivastava
Associate Professor
Dept. of Physiology

2. Learning objectives
• Introduction.
• Concepts in aging
• Theories of aging
• Aging of human physiological systems
• Aging slowly

3. • AGE : length of time the individual has existed
• AGING / SENESENCE : it’s a natural process.
• Time related deterioration of the physiological
functions necessary for survival and fertility.
• Aging is influenced by diet, environment
genetics as well as by personal habits.

4. Physiological Point….BASIC CAUSE ????
• It is a progressive constriction of the
homeostatic reserve of every organ system
• Decline of homeostatic reserve –
homeostenosis – gradual and progressive

7. • Science of aging : Gerontology
• Scientist - Gerontologists
• Branch : Geriatric medicine

8. Age - associated diseases
• Diseases that do not cause morbidity or mortality
until advanced ages
• Primary ageing : intrinsic changes occuring with age,
unrelated to disease or environmental influences
• Secondary ageing : changes caused by interaction of
primary ageing with environmental influences or
disease processes

9. Theories of aging
• A- Genetic theories-
1- Mutation Theory
2- Pleotropic Antagonigm
3- Ecological theory
• B- Random damage
theories-
1- Free radical theory
2- Cell replication theory
3- Cross linking theory

10. AGING IS AN EVOLVED TRAIT
• 1. Mutation – accumulation mechanism
Deleterious mutations in gametes – defective
progeny – natural selection will remove such
genes from population
Few mutations which do not have deleterious
effect till advanced age – will not be
eliminated by natural selection

11. 2.Antagonistic pleiotropy
• Genes that have deleterious effect in late
ages , increases evolutionary fitness in adult
age so natural selection favors such alleles
because they have negative impact only after
reproduction……………..

12. 3. Ecological theory
• The ecological theory applies to the ecological
conditions where external hazards are less.
•
• In such favorable environments, the mutation is such
that the aging process is retarded to allow the animal
to reproduce and protect the off springs.

13. •Random Damage Theories
•The random damage theories explain that the aging is due to
the loss of balance between ongoing damage and repair.
•The continuous tissue damage in the body occurs due to
constant production of free radicals.
•Especially after the age of 40 years, capacity to repair cells,
tissues, and organs decline.
• Due to the arrest of the cell cycles at the G1/S phase. This
is the phase in cell cycle at which synthesis of DNA starts. Thus,
DNA synthesis is impaired.

15. REACTIVE OXYGEN SPECIES
• Hydrogen peroxide
• Hydroxyl radical – most reactive
• Superoxide anion radical
Imbalance between production and removal of
reactive oxygen species is the major cause of
ageing

16. Role of Free Radicals and Oxidative Stress
Due to metabolism, free radicals like peroxide and hydroxyl radicals
are continuously produced in the body.
These radicals damage the cells and tissues by the process of
oxidation.
The free radicals damage DNA and proteins and cause peroxidation of
lipids in the membranes. This is called oxidative stress.
Simultaneously a scavenging system of antioxidants also exists in the
body that neutralizes the toxic effects of free radicals.
Antioxidants include vitamin E, vitamin A, and vitamin C.
Enzymatic defense : SODs, catalase and glutathione, peroxidase
Oxidative stress becomes more when production of oxidants is more
than the generation of antioxidants.
 Oxidative stress promotes aging.

18. 1. Limitations in cell division
 Hayflick limit : fibroblast can divide only for
limited number of times
Concept of telomeres

20. • Role of Cell Replication
• In recent times, the length of telomeric DNA has also
been associated to cell replication. Telomeric DNA is
present at the ends of chromosomes. Telomeric DNA
has following important functions:
1. Prevents chromosomal instability.
2. Slows chromosomal fragmentation and
rearrangement
3. Anchors chromosomes to nuclear matrix.
4. Acts as a buffer between coding regions of DNA
and the ends of the chromosomes.
5. It is also necessary for cell divisions

23. GLYCATION HYPOTHESIS OF AGEING

24. Schiff base – Melanoidins – pentosidine and
carboxymethyllysine
AGE associated long term complications of
diabetes, lens proteins in eyes – opacification,
stiffness of collagen in connective tissue, DNA
repair damage – aging

25. Mitochondrial theory of ageing
• Damage to mtDNA reduces ability of
mitochondria to generate ATP, LOSS OF CELL
FUNCTION & hence ageing

26. DNA damage theory of ageing
• DNA damage due to radiations, oxidative
damage
• Accumulated damaged DNA interferes with
normal DNA replication and transcription –
impairs cells ability to function – ageing

27. 2. Protein turn-over
• Changes in primary and secondary structure of
protein – causes aggregation and
fragmentation of protein molecule – interferes
with protein function
• Protecting the organism from this degradation
is called protein turn over
• This decreases with age – causes ageing

28. 3. MEMBRANE DETERIORATION
• In phospholipid bilayer – high amount of PUFA
is present – oxidative process generates lipid
peroxides from it and damage membrane
• Cell rapidly replaces it with membrane lipids
which alter its structure and interferes with
barrier function, signaling and transport
processes ……….

29. Ageing of human physiological systems

31. • Ageing people loose height and lean body
mass but gain and redistribute fat……
• Loose height ??? – compression of
cartilagenous disc - 2.5 to 5 %
• Fat free mass = body mass – adipose tissue fat
mass
• Lean body mass = fat free – bone & non
adipose tissue mass

33. • Decreased arterial compliance : atherosclerosis
• Mismatched V/P ratio : COPD
• Increased SBP
• Decreased DBP
• Wide PP
• Postural hypotension
• Atelactasis
• VO2 max : decreases with age
• Exercise capacity reduces
• GFR declines with age
• Frequency of micturition : increased , reduces bladder
compliance

35. • Liver mass and hepatic blood flow decreases ,
difficulty in regeneration if damage occurs
• Insulin resistance
• Increased LDL
• Peak concentrations of hormones decreases
• DHEA activity decreases , cortisol and
aldosterone well preserved
• Parathyroid level increases
• Menopause and andropause

36. SKELETAL MUSCLES

37. • Sarcopenia
• Muscle fibres
• Innervation ratio – recruitment

38. BONE & JOINTS

39. • Disbalance between osteoblastic and clastic
activity
• Bone mineral density index
• Osteoporosis
• More in women
• Ageing of articular cartilage – stiffening –
osteoarthritis

41. Sensory functions
• Deterioration with age
• Touch , vibrations, 2 point discrimination,
proprioception , pressure, thermoregulation :
decreases with age
• Hearing loss – high frequency
• Presbyobia – weaking of lens
• Reduced taste and olfaction

42. Motor functions
• Slowing of reaction time
• Delayed central processing

43. Cognitive functions
• Intelligence : does not decline
• Capacity to use knowledge does not decline in
healthy elderly
• Solve new problems, where r car keys ,
learning is slowed

46. AGEING SLOWLY ……………

47. Food restriction
• Restriction of specific component
( C,P,F ) ?????
• Reduces oxidative stress , reduce glycation
and glyco-oxidation, reductions in plasma level
of insulin and IGF-1
• Food restriction – Decrease oxidative stress &
stimulate maintenance and repair – retard
ageing

48. Role of Calorie Intake
•Increased calorie intake after 40 yrs has been proved to facilitate aging.
•The calorie restriction by about 20-30% of the total calorie intake has been
documented to have following effects:
1. Increase in average life expectancy and maximum life span.
2. Delay in onset of age-associated diseases.
3. Decrease in deterioration of physiologic processes like immune
responsiveness, glucose metabolism, muscle atrophy, etc.
4. Influence on gene expression, protein turnover, and crosslinking.
5. Calorie restriction must be supplemented with vitamins and antioxidants
to prevent aging.

49. EXERCISE
• There is still no conclusive evidence to document
that exercise prevents ageing or not.
• Exercise improves work capacity as assessed
from maximum oxygen uptake.
• Physical exercise improves cardiac performance
and reduces musculoskeletal disability.
• Physical exercise is reported to prevent age-
related decline in resting metabolic rate.

50. • Interventions to slow aging and extend human
life are controversial
• Exercise , diet , magic bullets ( anti-oxidants
and hormones )
• Recombinant GH ??????????????????????