Ageing is caused by the progressive loss of structural and functional capacity in cells over time, leading to death. It is influenced 60% by genetic factors and 40% by environmental factors such as trauma, disease, diet, and stress. The main structural and biochemical changes that occur during ageing include the accumulation of oxidative damage in cells from reactive oxygen species, advanced glycation end products, and abnormally folded proteins. Telomerase plays a role in preventing shortening of telomeres during cell division. Restricting calorie intake and maintaining good health habits can help delay the cellular ageing process.

2. Ageing:
“Progressive time related loss of structural and functional
capacity of cells leading to death”
 Senescence, Senility, Senile changes.
 Ageing of a person is intimately related to cellular ageing.

3. Factors affecting Ageing:
 Genetic 60% & Environmental 40%
 Clock genes, (fibroblast culture)
 Werner’s syndrome.
 Age gene on Chromosome 1.
 “Age” is a character from female parent.
 Mammalian mitochondria come from ovum.

4. Factors affecting Ageing:
 Environmental factors (40%)
 Trauma
 Diseases – Atherosclerosis, diabetes
 Diet – malnutrition, obesity etc.
 Psychological & Social health – stress.

5. 1. FUNCTIONALLY:
Oxidative phosphorylation by mitochondria
Synthesis of Nucleic Acid and enzymatic protein
Capacity for uptake of nutrients
Capacity to repair DNA damage.
STRUCTURAL & BIOCHEMICAL CHANGES:

6.  Irregular and abnormally lobed nuclei.
 Pleomorphic, vacuolated mitochondria
 Decreased ER.
 Distorted Golgi apparatus.
2. MORPHOLOGICALLY:

7. Accumulation of :
1. Pigment Lipofuscin which is an evidence of oxidative
damage of the cell.
2. Advanced Glycation End products (AGE’s).
3. Abnormally folded proteins.
3. BIOCHEMICAL CHANGES:

8. LIPOFUSCIN:
 Also called as lipochrome (or)/ wear and tear pigment (or)
aging pigment.
 Derived through lipid peroxidation of polyunsaturated lipids of
sub cellular membranes.
 Reactive oxygen species cause covalent modification of Lipids;
thus producing lipofuscin.
 It is the tell tale sign of free radical injury and oxidative damage.

9.  ECM Components:
1. Abnormal matrix –matrix and matrix –cell interactions,
2. Cross-linking of polypeptides of same protein,
3. Trapping of non-glycated proteins,
4. AGE’s cross-linked proteins are resistant to Proteolytic
digestion.

10. ACCUMULATION OF ABNORMALLY FOLDED PROTIEN:
 In the process of folding, partially folded Intermediates arise,
and these may form intracellular aggregates among them
selves (or) by entangling other proteins.

11. CHAPERONES:
 Chaperones are part of Heat- Shock Proteins.
 Chaperones attach on nascent polypeptide chains & prevent
wrong folding; so that folding is allowed in correct direction. Aid
in proper folding.
 Transport across the ER, GC.
 If folding process is un successful the chaperones facilitate
degradation of damaged protein.
 This process involves ubiquitin (HSP) which is added to the
abnormal protein & marks it for degradation by proteasome
complex.

12. Telomerase:
 Normally, at each division there is gene loss, finally the stability of
chromosome is lost.
 Human telomere end contains (TTAGGG) at 3’ end.
 Shortening of telomere end is prevented by enzyme Telomere
terminal transferase (or) Telomerase.
 In normal somatic cells, telomerase activity is decreased by
regulatory proteins.
 Telomerase activity is expressed in germ cells and stem cells only.

13. ???? Cancer--Telomerase
 Conversely, in immortal cancer cells, telomerase is
reactivated and telomeres are not shortened.
 Therefore there is continuous division of cells in
carcinoma.

14. GENES THAT INFFUENCE AGEING:
 Genes controlling Insulin /IGF-1 pathway.
 Decreased signals from IGF-1 receptor result in prolonged
life span in experimental animals.
 Down stream of signals of IGF-1 receptor is due to:
1. Decreased calorie intake.
2. Kinases which lead to silencing of genes that promote
aging.

15. DISEASE DEFECT
WERNER Syndrome DNA helicase
(Protein involved in DNA
replication and repair and DNA
un winding)
Ataxia telangiectasia Mutated ATM gene codes a
protein involved in repair of
double strand breaks in DNA.
Xeroderma Pigmentosum Defect in Nucleotide Excision
Repair mechanism.
Fanconi’s Anemia Defect in DNA cross link repair.

16. Ageing – Morphologic changes:
 Skin – elastosis, hairloss, atrophy, bruising.
 Joints – osteoarthritis.
 Immunity – immunosuppression.
 Heart – Brown atrophy,
 CVS – arterio & atherosclerosis, MI, stroke.
 Neoplasms
 CNS – cerebral degeneration.

17. Conclusion:
The cellular aging process is influenced by genetic factors
and also environmental factors and personal habits.
Delay in aging occurs mostly because of restriction in
caloric intake.
Adaptation of good health habits such as increase intake
of antioxidants and avoiding excess usage of DNA repair
inhibitors E.g., most of Antibiotics.

18. Yesterday is “History”
Tomorrow is a “Mystery”
Today is the gift.
That is why it is called “Present”