Hormesis does not make sense except in the light of TOR-driven aging

被引:61
作者
Blagosklonny, Mikhail V. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, Buffalo, NY 14263 USA
来源
AGING-US | 2011年 / 3卷 / 11期
关键词
Hormesis; aging; senescence; rapamycin; mTOR; damage; diseases; LIFE-SPAN EXTENSION; MESSENGER-RNA TRANSLATION; ACTIVATED PROTEIN-KINASE; SMALL-MOLECULE ACTIVATORS; HYPOXIA-INDUCIBLE FACTOR; OXIDATIVE DAMAGE THEORY; MAMMALIAN TARGET; CALORIE RESTRICTION; DIETARY RESTRICTION; CAENORHABDITIS-ELEGANS;
D O I
10.18632/aging.100411
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Weak stresses (including weak oxidative stress, cytostatic agents, heat shock, hypoxia, calorie restriction) may extend lifespan. Known as hormesis, this is the most controversial notion in gerontology. For one, it is believed that aging is caused by accumulation of molecular damage. If so, hormetic stresses (by causing damage) must shorten lifespan. To solve the paradox, it was suggested that, by activating repair, hormetic stresses eventually decrease damage. Similarly, Baron Munchausen escaped from a swamp by pulling himself up by his own hair. Instead, I discuss that aging is not caused by accumulation of molecular damage. Although molecular damage accumulates, organisms do not live long enough to age from this accumulation. Instead, aging is driven by overactivated signal-transduction pathways including the TOR (Target of Rapamycin) pathway. A diverse group of hormetic conditions can be divided into two groups. "Hormesis A" inhibits the TOR pathway. "Hormesis B" increases aging-tolerance, defined as the ability to survive catastrophic complications of aging. Hormesis A includes calorie restriction, resveratrol, rapamycin, p53-inducing agents and, in part, physical exercise, heat shock and hypoxia. Hormesis B includes ischemic preconditioning and, in part, physical exercise, heat shock, hypoxia and medical interventions.
引用
收藏
页码:1051 / 1062
页数:12
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