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Cellular Senescence and Pathways in Aging

Aging is a natural aspect of life. Understanding the various mechanisms that cause the progressive decline of cellular and tissue function may aid in developing therapies to delay or treat age-related conditions and diseases. 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.