Dr. Priya Patil's seminar on biochemistry of aging covers several key topics: 1) Definitions of aging as a progressive decline in structure and function over time. 2) Theories of aging including evolutionary, wear and tear, free radical, and telomere shortening theories. 3) Molecular mechanisms of aging including reactive oxygen species, protein glycation, impaired autophagy and DNA repair. 4) Strategies to increase healthspan and delay aging effects through diet, exercise, and potential drugs.

1. Biochemistry of aging
Dr. Priya Patil

3. Objectives of the seminar
• Define Aging
• Components of Aging
• Theories and Cellular processes of Aging
• Aging changes in specific tissues
• Genetic influences on Aging
• Gene studies in long lived centenarians
• Molecular repair mechanisms to combat wear
and tear
• Strategies to increase health span and delay
Aging

4. Define Aging
• Aging is easy to recognise but difficult to define.
• Most definitions of aging indicate that it is a
progressive process associated with declines in
structure and function, impaired maintenance and
repair systems, increased susceptibility to disease
and death and reduced reproductive capacity.

5. • Components of Aging
Statistical component Phenotypic component

6. • Theories of Aging
Evolutionary theories -
Biological/physiological theories-

7. Evolutionary theories
• Programmed death
• Mutation accumulation
• Antagonistic pleiotrophy
• Life history theory
• Disposable soma theory

8. Biological/Physiological theories
• Wear and tear theory
-hydrolytic reactions can damage proteins and
nucleotides.
- Generation of reactive oxygen species.
• Free radical and mitochondrial theory of aging
• UV induced free radical generation
• Protein glycation- AGE’s

9. • Hydrolytic reactions

10. •Reactive oxygen species

12. Free radical and mitochondrial theory
of aging-
“Free radical theory of aging”- Denham Harmon
Life span α 1
metabolic rate
Mitochondria are key participitants in apoptosis

13. Telomere shortening and replicative
senescence
• Secondary to hayflick limit
• Cellular clock
• Neurons also age

14. Altered gene expression, Epigentics,
miRNA
• Eg: histone acetylation is regulated by many
enzymes including SIRT 1, a protein that has
marked effect on aging.
• Specific miRNA are linked to aging pathways
like miR-21 (asso with target of rapamycin
pathway) and miR-1 (asso with insulin/IGF
pathway)

15. Impaired autophagy
Lysosomal system,
Ubiquitin proteosomal system
Lipofuscin,
Aggregated proetins

16. UV rays can be extremely damaging
UV Rays

17. Protein glycation
• Protein glycation often links to the formation of covalent cross
links between two proteins or other biological
macromolecule.
• These cross linked aggregates are sometime called as AGE’s.
• Eg: the progressive crosslinking of collagen network in
vascular endothelial cells leads to the progressive loss of
elasticity and thickening of basement in blood vessels
promoting plague formation.

18. Aging changes in specific tissue that
predispose to disease
• Immune system- decreased T- cells and overproduction of
autoantibodies by B-cells
• Liver- impaired detoxification, decreased hepatic clearance
• Vascular changes- atherosclerosis, myocardial interstitial fibrosis
• Sensory- lacrimal gland atrophy, corneal degenerations, cataract etc
• Endocrine –hypogonadism and bone diseases.

19. Molecular repair mechanisms- combat
wear and tear
• Enzymatic and chemical mechanism intercept
damaging ROS.
• The integrity of DNA is maintained by proof
reading and repair mechanism
• Routine turnover
• Aggregated proteins

20. Genetic influences on Aging

21. Werner syndrome: defect in WRN gene coding
for RecQ helicase

22. Mutation in Lamin A gene producing an
abnormal protein called progerin

24. Cockayne syndrome: mutation in DNA excision
repair proteins ERCC-6 and ERCC-8

25. Gene studies in long lived centenarians
• APO E
• FOXO 3A
• Certain SNP’s

26. Strategies to increase health span and
delay Aging
Diet restriction
Exercise
Drugs –
revereratol,
rapamycin,
spermidine,
metformin

29. Metformin the first anti-aging drug

35. Biomarkers of aging

39. Everolimus

40. Trade off between cells

41. GDF 11- promotes fast healing

42. Nanog: stem cell gene