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Cap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol
dc.contributor.authorShen, Ziqian
dc.contributor.authorHinson, Abby
dc.contributor.authorMiller, Richard A.
dc.contributor.authorGarcia, Gonzalo G.
dc.date.accessioned2021-06-02T21:10:29Z
dc.date.available2022-06-02 17:10:27en
dc.date.available2021-06-02T21:10:29Z
dc.date.issued2021-05
dc.identifier.citationShen, Ziqian; Hinson, Abby; Miller, Richard A.; Garcia, Gonzalo G. (2021). "Cap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol." Aging Cell (5): n/a-n/a.
dc.identifier.issn1474-9718
dc.identifier.issn1474-9726
dc.identifier.urihttps://hdl.handle.net/2027.42/167855
dc.description.abstractWe 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.ACA, Rapamycin and 17alfa Estradiol downregulate mTORC1 activity and upregulation of the Cap‐Independent Translation leading to increases in the levels of cap‐Independent associated proteins (involved in mitochondrial function and stress resistance), suggesting a possible mechanism for lifespan extension.
dc.publisherWiley Periodicals, Inc.
dc.subject.otheraging
dc.subject.otherprotein translation
dc.subject.otherrapamycin
dc.subject.othersignal transduction
dc.subject.otheracarbose
dc.subject.other17α‐estradiol
dc.titleCap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/167855/1/acel13345_am.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/167855/2/acel13345.pdf
dc.identifier.doi10.1111/acel.13345
dc.identifier.sourceAging Cell
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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