Selvarani Ramasamy, Mohammed Sabira, Richardson Arlan
Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Oklahoma City VA Medical Center, Oklahoma City, OK, USA.
Geroscience. 2021 Jun;43(3):1135-1158. doi: 10.1007/s11357-020-00274-1. Epub 2020 Oct 10.
In 2009, rapamycin was reported to increase the lifespan of mice when implemented later in life. This observation resulted in a sea-change in how researchers viewed aging. This was the first evidence that a pharmacological agent could have an impact on aging when administered later in life, i.e., an intervention that did not have to be implemented early in life before the negative impact of aging. Over the past decade, there has been an explosion in the number of reports studying the effect of rapamycin on various diseases, physiological functions, and biochemical processes in mice. In this review, we focus on those areas in which there is strong evidence for rapamycin's effect on aging and age-related diseases in mice, e.g., lifespan, cardiac disease/function, central nervous system, immune system, and cell senescence. We conclude that it is time that pre-clinical studies be focused on taking rapamycin to the clinic, e.g., as a potential treatment for Alzheimer's disease.
2009年,有报道称雷帕霉素在小鼠生命后期使用时可延长其寿命。这一观察结果使研究人员对衰老的看法发生了翻天覆地的变化。这是首个表明一种药物制剂在生命后期给药时可对衰老产生影响的证据,即一种不必在衰老产生负面影响之前于生命早期实施的干预措施。在过去十年中,研究雷帕霉素对小鼠各种疾病、生理功能和生化过程影响的报告数量激增。在本综述中,我们重点关注那些有确凿证据表明雷帕霉素对小鼠衰老及与年龄相关疾病有影响的领域,例如寿命、心脏病/心脏功能、中枢神经系统、免疫系统和细胞衰老。我们得出结论,现在是时候将临床前研究重点放在将雷帕霉素推向临床了,例如作为治疗阿尔茨海默病的一种潜在药物。