Cellular Ageing and Cellular Senescence. ppt

Cellular Ageing and Cellular Senescence

1. DR. P. SHINY LATHA CELLULAR AGEING CELLULAR AGEING DR. P. SHINY LATHA M.B.B.S., M.D.,

2. CELLULAR AGEING Cellular Ageing is the result of Progressive decline of cellular function & viability caused by  Genetic Abnormalities  Accumulation of Cellular & Molecular damage Due to the effects of exposure to exogenous influences

3. DNA DAMAGE Threaten the integrity of nuclear & mitochondrial DNA

4. Werner Syndrome – DNA helicase (replication & repair) Bloom Syndrome ageing at Ataxia telangiectasia increased rate

5. CELLULAR SENESCENCE All normal cells have a limited capacity for replication After a fixed number of divisions, cells become arrested In a terminally nondividing state = REPLICATIVE SENESCENCE Ageing is ass. with progressive replicative senescence of cells Cells of children > adults= replicates

6. CELLULAR SENESCENCE

7. TELOMERE Short repeated sequences of DNA The ends of linear chromosomes Important for ensuring the complete replication of chromosomal ends and for protecting the ends from fusion and degradation

8. TELOMERASE Telomere length is maintained by nucleotide addition mediated by an enzyme= TELOMERASE Specialized RNA- protein complex that uses its own RNA as a template for adding nucleotides to the ends of chromosomes

9. Cells of the body

10. Germ cells- gives rise to the gametes of an organism that reproduces sexually

11. Stem cells are undifferentiated cells that have the capacity to both differentiate and multiply into 200 cell types that form human being

12. Telomerase absent Telomerase reactivated Telomerase – low levels Telomerase – sufficient levels

13. ACTIVATION OF TUMOR SUPPRESSOR GENES CDKN2A locus – encodes tumor suppressor proteins (p16or INK4a) By controlling G1 to S phase of cell cycle  p16 protects the cell from uncontrolled mitogenic signals & pushes cells along the senescence pathway

14. DEFECTIVE PROTEIN SYNTHESIS Normal protein folding conformation & degradation of misfolded proteins  impaired with ageing

15. DYSREGULATED NUTRIENT SENSING Caloric restriction

16. SIRTUINS A family of NAD- dependent protein deacetylases Promote expression of genes whose products increase longevity - proteins that inhibit metabolic pathway - reduce apoptosis - stimulate protein folding - counteract the harmful effects of oxygen free radicals Increase insulin sensitivity & glucose metabolism  may be targets for the Rx of diabetes

17. SIRTUINS- anti ageing effects