Researchers: Joan B Mannick, Dudley W Lamming
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.
References
- Lysosome: The metabolic signaling hub.
- FoxO.
- Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice.
- Rapamycin treatment early in life reprograms aging: hyperfunction theory and clinical practice.
- Hypothalamic mTORC2 is essential for metabolic health and longevity.
- Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice.
Topic: healthspan (Graph Available)