Targeting the biology of aging with mTOR inhibitors.

Targeting the biology of aging with mTOR inhibitors.
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DOI:
10.1038/s43587-023-00416-y
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发表时间:
2023-06
期刊:
NATURE AGING
影响因子:
--
通讯作者:
Lamming, Dudley W.
Lamming, Dudley W.
中科院分区:
其他
文献类型:
--
作者:
Mannick, Joan B.;Lamming, Dudley W.

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FDA批准的雷帕霉素治疗药物抑制蛋白激酶mTOR可促进不同模式生物的健康和寿命。最近,特异性抑制mTORC1治疗衰老相关疾病已成为基础和转化型科学家、临床医生和生物技术公司的目标。在这里,我们回顾了雷帕霉素对野生型小鼠和人类疾病小鼠模型的寿命和存活率的影响。我们讨论了最近的临床试验,这些试验探索了现有的mTOR抑制剂是否可以安全地预防、延迟或治疗多种衰老疾病。最后,我们讨论了新分子如何在未来十年提供更安全和更具选择性的mTORC1抑制途径。最后,我们讨论了为了使mTOR抑制剂成为老年疾病护理标准的一部分,仍有哪些工作要做,以及需要解决的问题。
Inhibition of the protein kinase mTOR with the 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 if 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 mTORC1 in the decade ahead. We conclude by discussing what work remains to be done and the questions that will need to be addressed in order to make mTOR inhibitors part of the standard of care for diseases of aging.
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