Revisiting the antagonistic pleiotropy theory of aging TOR-driven program and quasi-program

被引:128
作者
Blagosklonny, Mikhail V. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA
关键词
mTOR; rapamycin; target of rapamycin; aging; cancer; diseases; menopause p53; senescence; cell cycle; EXTENDS LIFE-SPAN; DNA-DAMAGE RESPONSE; REGULATES LONGEVITY; CALORIE RESTRICTION; CELLULAR SENESCENCE; TUMOR SUPPRESSION; MAMMALIAN TARGET; DAUER FORMATION; P53; PATHWAY; MTOR;
D O I
10.4161/cc.9.16.13120
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
A half century ago, the antagonistic pleiotropy (AP) theory had solved a mystery of aging, by postulating genes beneficial early in life at the cost of aging. Recently it was argued however that there are very few clear-cut examples of antagonistically pleiotropic (AP) genes other than p53. In contrast, here I discuss that p53 is not a clear-cut example of AP genes but is rather an aging-suppressor (gerosuppressor). In contrast, clear-cut examples of AP genes are genes that encode the TO R (target of rapamycin) pathway. TO R itself is the ultimate example of AP gene because its deletion is lethal in embryogenesis. Early in life the TO R pathway drives developmental program, which persists later in life as an aimless quasi-program of aging and age-related diseases.
引用
收藏
页码:3151 / 3156
页数:6
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