用 mTOR 抑制剂靶向衰老的生物学。
Targeting the biology of aging with mTOR inhibitors.
机构信息
Tornado Therapeutics, New York, NY, USA.
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
出版信息
Nat Aging. 2023 Jun;3(6):642-660. doi: 10.1038/s43587-023-00416-y. Epub 2023 May 4.
Inhibition of the protein kinase mechanistic target of rapamycin (mTOR) with the Food and Drug Administration (FDA)-approved therapeutic rapamycin promotes health and longevity in diverse model organisms. More recently, specific inhibition of mTORC1 to treat aging-related conditions has become the goal of basic and translational scientists, clinicians and biotechnology companies. Here, we review the effects of rapamycin on the longevity and survival of both wild-type mice and mouse models of human diseases. We discuss recent clinical trials that have explored whether existing mTOR inhibitors can safely prevent, delay or treat multiple diseases of aging. Finally, we discuss how new molecules may provide routes to the safer and more selective inhibition of mTOR complex 1 (mTORC1) in the decade ahead. We conclude by discussing what work remains to be done and the questions that will need to be addressed to make mTOR inhibitors part of the standard of care for diseases of aging.
蛋白激酶雷帕霉素靶蛋白（mTOR）的抑制剂雷帕霉素已获美国食品药品监督管理局（FDA）批准，用于治疗多种疾病。最近，人们的目标是特异性抑制 mTORC1 以治疗与衰老相关的疾病，这一目标吸引了基础和转化科学家、临床医生以及生物技术公司的关注。在此，我们综述了雷帕霉素对野生型小鼠和人类疾病小鼠模型的寿命和生存的影响。我们讨论了最近的临床试验，这些试验探讨了现有的 mTOR 抑制剂是否可以安全地预防、延缓或治疗多种衰老相关疾病。最后，我们讨论了新分子如何为未来十年更安全、更有选择性地抑制 mTOR 复合物 1（mTORC1）提供途径。我们在讨论中总结了仍需完成的工作以及需要解决的问题，以使 mTOR 抑制剂成为衰老相关疾病治疗标准的一部分。
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