MEDICAL COUNCIL OF INDIA, COMPETENCY BASED UNDERGRADUATE CURRICULUM FOR THE INDIAN MEDICAL GRADUATE, 2018

1. PA2.7, K, KH, N
DESCRIBE & DISCUSS
MECHANISM OF AGING
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512

2. TEXTBOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• OTHER STANDARD REFRENCES

3. CELLULAR AGING
DEFINITION
Cellular aging is characterized by progressive
decline in
• functional capacity &
• life span of cell

4. CELLULAR AGING
FACTORS INCREASING AGING
• DNA DAMAGE
• DECREASED CELL REPLICATION – telomers &
telomerase
• DEFECTIVE PROTEIN HOMEOSTASIS

6. DNA DAMAGE
GENETIC
• BLOOM SYNDROME & ATAXIA-
TELANGIECTASIA- defective DNA repair genes-
increased rate of aging
ACQUIRED
• Exogenous agents & ROS damage DNA

7. CELLULAR SENESCENCE
( termination of cellular replication )
• TELOMERE ATTRITION – progressive
shortening of telomeres leading to cell cycle
arrest, telomere length is maintained by
enzyme telomerase.
• ACTIVATION OF TUMOR ( CELL
PROLIFERATION ) SUPPRESSOR GENES
prevents proliferation of cells by preventing
cell from going from G1 to S phase.

8. DEFECTIVE PROTEIN HOMEOSTASIS
Due to decreased synthesis of proteins &
accumulation of misfolded proteins
LEADS TO
• Malfunction of proteins
• Apoptosis

9. CELLULAR AGING
FACTORS DECREASING AGING
• INCREASED SIRUTIN
• DECREASED CALORIE INTAKE
• DECREASE INSULIN LIKE GF
• REDUCED KINASE ACTIVATION

10. DECREASE CELLULAR AGING
• DECREASE INSULIN LIKE GROWTH FACTOR-1 &
KINASE ACTIVITY – improve DNA repair,
protein homeostasis & immunity
• INCREASED SIRUTINS – proteins ( 7 types ) –
activate DNA repair
• CALORIE RESTRICTION – decreases IGF-1 &
increases SIRUTINS