title: Geroconversion: irreversible step to cellular senescence.
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.
authors.affiliation: a Cell Stress Biology; Roswell Park Cancer Institute ; Buffalo , NY USA.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D013312:Stress, Physiological / Q000502:physiology*
keywords: aging; cell cycle arrest; gerogenic conversion; mTOR; oncogenic trsnformation