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. 2023 Oct 6;45(5):2769–2783. doi: 10.1007/s11357-023-00935-x

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© The Author(s), under exclusive licence to American Aging Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Fig. 2 — Rapamycin acutely and potently inhibits mTORC1 while prolonged exposure to high, daily doses of rapamycin can lead to off-target inhibition of mTORC2. We propose to test the model that inhibition of mTORC1 is geroprotective, while inhibition of mTORC2 mediates metabolic side effects of rapamycin. Rapalog strategies that safely exploit the potent geroprotective effects of mTORC1 inhibition may warrant further testing for the treatment and prevention of age-related diseases in larger phase 3 clinical trials