Cellular aging is characterized by a decline in function due to genetic issues and accumulated damage from external factors. Key mechanisms include DNA damage that sometimes evades repair, replicative senescence marked by limited cell division, and impaired protein homeostasis. Dysregulated nutrient sensing, particularly through caloric restriction, can influence aging and longevity by modulating specific signaling pathways.

1. CELLULAR AGEING
• Cellular aging is the result of a progressive decline in cellular function and
viability caused by genetic abnormalities and the accumulation of cellular and
molecular damage due to the effects of exposure to exogenous influences
General features
DNA Damage
• Exogenous (physical, chemical, and biologic) agents and endogenous factors
such as ROS cause DNA damage.
• Although most DNA damage is repaired by DNA repair enzymes, some persists
and accumulates as cells age
• Mutations in DNA repair genes – Pre mature ageing
Cellular Senescence
• All normal cells have a limited capacity for replication, and after a fixed number
of divisions cells become arrested in a terminally nondividing state, known as
replicative senescence
• Telomere attrition
• Activation of tumor suppressor genes
Defective Protein Homeostasis
• Two mechanisms involved in protein homeostasis:
• Maintenance of proteins in their correctly folded conformations (mediated by
chaperones) and degradation of misfolded, damaged, or unneeded proteins by
the autophagy-lysosome system and ubiquitinproteasome system
• Both of which is impaired in ageing
Dysregulated Nutrient Sensing
• Caloric restriction increases life span by reducing the signaling intensity of the
IGF-1 pathway and by increasing sirtuins.
• Sirtuins: Designed to adapt bodily functions to various environmental stresses,
including food deprivation and DNA damage. increase longevity. may be targets
for the treatment of diabetes.