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• W3136673049 abstract "We hypothesized that rapamycin (Rapa), acarbose (ACA), which both increase mouse lifespan, and 17α-estradiol, which increases lifespan in males (17aE2) all share common intracellular signaling pathways with long-lived Snell dwarf, PAPPA-KO, and Ghr−/− mice. The long-lived mutant mice exhibit reduction in mTORC1 activity, declines in cap-dependent mRNA translation, and increases in cap-independent translation (CIT). Here, we report that Rapa and ACA prevent age-related declines in CIT target proteins in both sexes, while 17aE2 has the same effect only in males, suggesting increases in CIT. mTORC1 activity showed the reciprocal pattern, with age-related increases blocked by Rapa, ACA, and 17aE2 (in males only). METTL3, required for addition of 6-methyl-adenosine to mRNA and thus a trigger for CIT, also showed an age-dependent increase blunted by Rapa, ACA, and 17aE2 (in males). Diminution of mTORC1 activity and increases in CIT-dependent proteins may represent a shared pathway for both long-lived-mutant mice and drug-induced lifespan extension in mice." @default.
• W3136673049 created "2021-03-29" @default.
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• W3136673049 date "2021-03-20" @default.
• W3136673049 modified "2023-10-12" @default.
• W3136673049 title "Cap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol" @default.
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• W3136673049 doi "https://doi.org/10.1111/acel.13345" @default.
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