Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice
复制标题
DOI：
10.1093/gerona/glw064
复制
发表时间：
2016-07-01
影响因子：
5.1
通讯作者：
Lamming, Dudley W.
中科院分区：
文献类型：
--
作者：
Apelo, Sebastian I. Arriola;Pumper, Cassidy P.;Lamming, Dudley W.
通过FDA批准的药物雷帕霉素抑制mTOR（雷帕霉素的机械靶点）信号传导途径，可以延长许多模型生物的寿命，并延缓小鼠的年龄相关疾病。然而，由于雷帕霉素在人类中的严重代谢和免疫副作用，利用雷帕霉素作为年龄相关疾病的治疗可能会证明具有挑战性。我们最近确定了一种间歇性雷帕霉素治疗方案-每5天给予2 mg/kg-与长期治疗相比，对葡萄糖稳态和免疫系统的影响减少;然而，这种方案延长寿命的能力尚未确定。在这里，我们首次报告了迟至20月龄开始的间歇性雷帕霉素治疗方案可以延长雌性C57 BL/6 J小鼠的寿命。我们的工作表明，雷帕霉素的抗衰老潜力与其许多负面副作用是分离的，并表明精心设计的给药方案可能允许更安全地使用雷帕霉素及其类似物治疗人类与年龄相关的疾病。
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-2 mg/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.