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
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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