The document discusses the physiology of aging and oxidative stress, outlining theories of aging, physiological changes in the elderly, and the role of oxidative stress and free radicals in degenerative processes. It highlights various genetic and random damage theories of aging, the impact of calorie intake on longevity, and the significance of antioxidants in mitigating oxidative stress. Furthermore, it addresses factors contributing to accelerated aging, such as atherosclerosis and lifestyle choices.

1. PY 11.7
Physiology of Aging and Oxidative
Stress
SGIT

2. 1. Name the theories of aging to understand the basic principle
of each.
2. List physiological changes in geriatric age.
3. Outline the basic mechanisms of oxidative stress.
4. Explain the role of free radicals causing degeneration of the
body.
5. Appreciate the role of antioxidants in preventing
degeneration of the body.
6. Comprehend the role of free radicals in pathophysiology
of common diseases
LEARNING OBJECTIVES

3. AGING
 Gradual Deterioration of ability of carrying out
Physiological Functions.
 It is irreversible and inevitable.
 It is of 2 types
 1) Chronological
 2) Biological--- Stress, Environment, Food (nutritional
status), Lifestyle, Genes etc.

4. SIGNS OF AGING
 Loss of Hair Pigment
 Development of Pigmented area on skin
 Dryness and wrinkling of Skin
 Loss of Agility
 Increased body weight due to Fat
 Poor Vision
 Forgetfulness
 Weakness and decreased Immunity
 Degradation of Organs and Tissues

5. Theories of Aging
The biological changes of aging are clearer than the
mechanisms that mediate it. The common changes
include:
1. Chromosomal abnormalities
2. Increased DNA cross-linking
3. Increased frequency of single-strand breaks in
DNA
4. Decrease in DNA methylation
5. Loss of DNA telomeric sequences
AGING

6. 6. Increased post-translational changes in proteins
7. Deamination, oxidation, and nonenzymatic glycation of proteins
8. Deformation in mitochondrial structure.
Aging is multifactorial
There are many theories of aging that are not completely compatible in
their explanation. However, they can be broadly divided into two categories:
 Genetic theories and
 Random damage theories

7. Genetic Theories of Aging
Genetic theories of aging are based on programmed
senescence, which means that at the time of birth the
time of aging and death has been predetermined. That
means the aging is preprogrammed by a biological time
table.
Three genetic theories have been developed
recently:
1. Mutation Theory
The first one is the mutation theory. Usually animals die
much before completion of their expected life span due
to adverse effects of natural forces. Therefore, this
theory suggests the importance of mutations that
retards long survival. The mutations pile up in the genes
that are transferred from generations to generations.

8. 2. Theory of Pleiotropic Antagonism
The second one is the theory of pleiotropic antagonism, which proposes that
aging is caused by the harmful effects of genes. These unfavorable genetic
effects are preserved for the purpose of survival and these properties are
imparted prior to reproduction.
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.

9. 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, and by the processes of oxidation and
glycation. However, the damage is immediately
repaired by regenerating an anti-stress mechanism.
With advancement of age, especially after the age
of 40 years, capacity to repair cells, tissues, and
organs decline. Regenerative senescence was also
suggested to be 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

10. 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

11. Role of Calorie Intake
Strongly implicated in aging is excess calorie consumption.
Increased calorie intake after the age of 40 has been proved
to facilitate aging. It has been observed that calorie
restriction delays the onset of aging. The calorie restriction
by about 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.

12. Role of Calorie Intake
 4. Influence on gene expression,
protein turnover, and crosslinking.
The impact of general calorie
restriction is different from specific
dietary restriction like restriction
for fat, etc. However, calorie
restriction must be supplemented
with vitamins and antioxidants to
prevent aging.

13. 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.
However, simultaneously a scavenging system of
antioxidants also exists in the body that neutralizes
the toxic effects of free radicals. Antioxidants
include glutathione, vitamin E, vitamin A, and
vitamin C. Oxidative stress becomes more when
production of oxidants is more than the generation
of antioxidants. Oxidative stress promotes aging.

14. Atherosclerosis
Atherosclerosis is the process of narrowing of lumen of
blood vessels due to deposition of lipid materials on the
inner endothelial lining of blood vessels. Atherosclerosis is
the physiological process that starts almost at infancy. In
childhood, atherosclerosis starts in aorta and larger
arteries. As age advances, atherosclerosis starts in smaller
arteries and arterioles. Due to atherosclerosis, blood
supply to organs and tissues of the body decreases that
causes structural and functional degenerations. This is the
natural process of degeneration (aging) and death.
However, the process of degeneration is facilitated by
accelerated atherosclerosis in which fibrofatty plaques
are deposited in greater amount in the blood vessel lumen
and hyperplasia of smooth muscle of blood vessels occur.
This causes premature aging and death.

15. The predisposing factors for
accelerated atherosclerosis are:
1. Hyperlipidemia (hypercholesterolemia,
hypertriglyceridemia)
2. Obesity
3. Diabetes mellitus
4. Hypertension
5. Smoking
6. Excess eating (increased calorie intake) after 40 years
of age
7. Chronic stress
8. Lack of exercise

18. ANTIOXIDANTS
 Group of Chemical Compounds that deactivate free
Radicals and prevent their formation.
 Stimulate Immune System and protect against all
diseases.
 These are
 Vitamin C
 Vitamin E
 Betacarotene
 Bioflavaonoids
 Minerals such as Selenium, Zinc, Copper etc.

19. FACTORS THAT WILL DELAY
AGING
 Not Smoking Cigarettes
 Maintaining Normal Weight
 Regular Exercise
 Overall Good Nutrition