Targeting the biology of aging with mTOR inhibitors

• Published in: Nature aging Vol. 3; no. 6; pp. 642 - 660
• Main Authors: Mannick, Joan B, Lamming, Dudley W
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.06.2023
• Subjects: Aging; Animals; Biology; Clinical trials; Humans; Kinases; Mechanistic Target of Rapamycin Complex 1; Mice; MTOR Inhibitors; Sirolimus; TOR Serine-Threonine Kinases; United States; United States
• ISSN: 2662-8465; 2662-8465
• DOI: 10.1038/s43587-023-00416-y

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.