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Rapamycin treatment during development extends life span and health span of male mice and Daphnia magna.


ABSTRACT: Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserve health as measured by frailty index scores, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome and epigenome of treated mice were younger at the completion of treatment. Analogous to mice, rapamycin exposure during development robustly extended the life span of Daphnia magna and reduced its body size. Overall, the results demonstrate that short-term rapamycin treatment during development is a novel longevity intervention that acts by slowing down development and aging, suggesting that aging may be targeted already early in life.

SUBMITTER: Shindyapina AV 

PROVIDER: S-EPMC9481125 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Rapamycin treatment during development extends life span and health span of male mice and <i>Daphnia magna</i>.

Shindyapina Anastasia V AV   Cho Yongmin Y   Kaya Alaattin A   Tyshkovskiy Alexander A   Castro José P JP   Deik Amy A   Gordevicius Juozas J   Poganik Jesse R JR   Clish Clary B CB   Horvath Steve S   Peshkin Leonid L   Gladyshev Vadim N VN  

Science advances 20220916 37


Development is tightly connected to aging, but whether pharmacologically targeting development can extend life remains unknown. Here, we subjected genetically diverse UMHET3 mice to rapamycin for the first 45 days of life. The mice grew slower and remained smaller than controls for their entire lives. Their reproductive age was delayed without affecting offspring numbers. The treatment was sufficient to extend the median life span by 10%, with the strongest effect in males, and helped to preserv  ...[more]

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