Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice

寿命 养生 PI3K/AKT/mTOR通路 药品 药理学 雷帕霉素的作用靶点 长寿 免疫系统 医学 加药 生物 生理学 免疫学 内科学 信号转导 老年学 细胞生物学
作者
Sebastian I. Arriola Apelo,Cassidy P Pumper,Emma L. Baar,Nicole E. Cummings,Dudley W. Lamming
出处
期刊:The Journals of Gerontology [Oxford University Press]
卷期号:71 (7): 876-881 被引量:136
标识
DOI:10.1093/gerona/glw064
摘要

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.
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