Cellular Senescence and Pathways in Aging

Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease. A variety of stressors, including strong mitogenic signals, DNA damage, and non-genotoxic chromatin perturbations cause cellular senescence - a state of permanent cell cycle arrest. Cellular senescence, although useful in young organisms to prevent cancer, is thought to promote aging. The most consistent determinant of life-span in eukaryotes is the mitogenic growth hormone/IGF-I pathway. However, premature aging syndromes caused by defects in the cellular response/repair to DNA damage indicate the role of accumulated damage. The complex biology of aging is impacted by both environmental and genetic factors: stochastic DNA damage causes decline of function, and genetics determines the rates of damage accumulation and functional decline.