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Geroconversion: irreversible step to cellular senescence.

Research paper by Mikhail V MV Blagosklonny

Indexed on: 09 Dec '14Published on: 09 Dec '14Published in: Cell cycle (Georgetown, Tex.)



Abstract

Cellular senescence happens in 2 steps: cell cycle arrest followed, or sometimes preceded, by gerogenic conversion (geroconversion). Geroconvesrion is a form of growth, a futile growth during cell cycle arrest. It converts reversible arrest to irreversible senescence. Geroconversion is driven by growth-promoting, mitogen-/nutrient-sensing pathways such as mTOR. Geroconversion leads to hyper-secretory, hypertrophic and pro-inflammatory cellular phenotypes, hyperfunctions and malfunctions. On organismal level, geroconversion leads to age-related diseases and death. Rapamycin, a gerosuppressant, extends life span in diverse species from yeast to mammals. Stress-and oncogene-induced accelerated senescence, replicative senescence in vitro and life-long cellular aging in vivo all can be described by 2-step model.