Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK.
Cell. 2011 Sep 2;146(5):682-95. doi: 10.1016/j.cell.2011.07.030.
Genetic inhibition of autophagy induces degenerative changes in mammalian tissues that resemble those associated with aging, and normal and pathological aging are often associated with a reduced autophagic potential. Pharmacological or genetic manipulations that increase life span in model organisms often stimulate autophagy, and its inhibition compromises the longevity-promoting effects of caloric restriction, Sirtuin 1 activation, inhibition of insulin/insulin growth factor signaling, or the administration of rapamycin, resveratrol, or spermidine. Here, we discuss the probable cause and effect relationship between perturbed autophagy and aging, as well as possible molecular mechanisms that may mediate the anti-aging effects of autophagy.
遗传抑制自噬会导致哺乳动物组织发生退行性变化，这些变化类似于与衰老相关的变化，而正常和病理性衰老通常与自噬潜能降低有关。在模型生物中，增加寿命的药理学或遗传学操作通常会刺激自噬，而其抑制会损害热量限制、Sirtuin 1 激活、抑制胰岛素/胰岛素生长因子信号传导或雷帕霉素、白藜芦醇或亚精胺给药的延长寿命作用。在这里，我们讨论了自噬失调与衰老之间可能的因果关系，以及可能介导自噬抗衰老作用的可能分子机制。
