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.

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.

Factors affecting Ageing:

Environmental factors (40%)

Trauma

Diseases – Atherosclerosis, diabetes

Diet – malnutrition, obesity etc.

Psychological & Social health – stress.

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:

Irregular and abnormally lobed nuclei.

Pleomorphic, vacuolated mitochondria

Decreased ER.

Distorted Golgi apparatus.

2. MORPHOLOGICALLY:

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:

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.

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.

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.

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 proteasomecomplex.

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.

???? Cancer--Telomerase

Conversely, in immortal cancer cells, telomerase is

reactivated and telomeres are not shortened.

Therefore there is continuous division of cells in

carcinoma.

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.

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.

Ageing – Morphologic changes:

Skin – elastosis, hairloss, atrophy, bruising.

Joints – osteoarthritis.

Immunity – immunosuppression.

Heart – Brown atrophy,

CVS – arterio & atherosclerosis, MI, stroke.

Neoplasms

CNS – cerebral degeneration.

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.

Yesterday is “History”

Tomorrow is a “Mystery”

Today is the gift.

That is why it is called “Present”