Senescence

• Hayflick & Moorehead (1961, in vitro): normal human cultured fibroblasts have a finite capacity for cell divisions before theyenter an irreversible growth arrest

• cause: telomere shortening

stable and terminal state of growth arrest, in which cells are unableto proliferate despite optimal growth conditions and mitogenic stimuli

• DNA damage response (DDR)

• Telomere shortening

• Oncogene activation

Telomeres are very successible to DNA damage due to their chromatin structure and sequence

Fate depends on modulation and status of p53

• p21 & p16

• SA-β-gal

• morphology

• lack of DNA replication

• heterochromatin

• SASP

Input: NFκB activity

Output: secretion of inflammatory factors & factors that impact ECM

• senescence is a driver of aging

  • accumulation of senescent cells causes aging phenotype

  • elimination of senescent cells rejuvinates, but does not reverse aging

  • elimination of senescent cells impairs wound healing