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Abstract
Many cellular stresses activate senescence, a persistent hyporeplicative state characterized
in part by expression of the p16(INK4a) cell-cycle inhibitor. Senescent cell production
occurs throughout life and plays beneficial roles in a variety of physiological and
pathological processes including embryogenesis, wound healing, host immunity, and
tumor suppression. Meanwhile, the steady accumulation of senescent cells with age
also has adverse consequences. These non-proliferating cells occupy key cellular niches
and elaborate pro-inflammatory cytokines, contributing to aging-related diseases and
morbidity. This model suggests that the abundance of senescent cells in vivo predicts
"molecular," as opposed to chronologic, age and that senescent cell clearance may
mitigate aging-associated pathology.