老年转化：细胞衰老的不可逆步骤。
Geroconversion: irreversible step to cellular senescence.
作者信息
Blagosklonny Mikhail V
机构信息
a Cell Stress Biology; Roswell Park Cancer Institute ; Buffalo , NY USA.
出版信息
Cell Cycle. 2014;13(23):3628-35. doi: 10.4161/15384101.2014.985507.
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.
细胞衰老分两个阶段发生
先是细胞周期停滞，随后（有时也先于）发生衰老性转化（geroconversion）。衰老性转化是一种生长形式，是细胞周期停滞期间的无效生长。它将可逆性停滞转变为不可逆的衰老。衰老性转化由促进生长、有丝分裂原/营养感应途径（如mTOR）驱动。衰老性转化导致高分泌、肥大和促炎细胞表型、功能亢进和功能失调。在机体水平上，衰老性转化导致与年龄相关的疾病和死亡。雷帕霉素是一种衰老抑制剂，可延长从酵母到哺乳动物等多种物种的寿命。应激和癌基因诱导的加速衰老、体外复制性衰老和体内终身细胞衰老都可以用两步模型来描述。
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