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dc.contributor.authorBirkisdóttir, María B
dc.contributor.authorJaarsma, Dick
dc.contributor.authorBrandt, Renata M C
dc.contributor.authorBarnhoorn, Sander
dc.contributor.authorvan Vliet, Nicole
dc.contributor.authorImholz, Sandra
dc.contributor.authorvan Oostrom, Conny T
dc.contributor.authorNagarajah, Bhawani
dc.contributor.authorPortilla Fernández, Eliana
dc.contributor.authorRoks, Anton J M
dc.contributor.authorElgersma, Ype
dc.contributor.authorvan Steeg, Harry
dc.contributor.authorFerreira, José A
dc.contributor.authorPennings, Jeroen L A
dc.contributor.authorHoeijmakers, Jan H J
dc.contributor.authorVermeij, Wilbert P
dc.contributor.authorDollé, Martijn E T
dc.date.accessioned2021-02-07T14:52:46Z
dc.date.available2021-02-07T14:52:46Z
dc.date.issued2021-01-23
dc.identifier.pmid33484480
dc.identifier.doi10.1111/acel.13302
dc.identifier.urihttp://hdl.handle.net/10029/624666
dc.description.abstractDietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair-deficient Ercc1∆/- mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were unable to alter life span. Even genetically modifying mTOR signaling failed to increase life span of DNA repair-deficient mice. The absence of effects by rapamycin on P53 in brain and transcription stress in liver is in sharp contrast with results obtained by DR, and appoints reducing DNA damage and transcription stress as an important mode of action of DR, lacking by rapamycin. Together, this indicates that mTOR inhibition does not mediate the beneficial effects of DR in progeroid mice, revealing that DR and rapamycin strongly differ in their modes of action.en_US
dc.language.isoenen_US
dc.rights© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
dc.subjectDNA damage repairen_US
dc.subjectagingen_US
dc.subjectdietary restrictionen_US
dc.subjectrapamycinen_US
dc.subjecttranscription stressen_US
dc.titleUnlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice.en_US
dc.typeArticleen_US
dc.identifier.eissn1474-9726
dc.identifier.journalAging Cell 2021; e13302 advance online publication (ahead of print)en_US
dc.source.journaltitleAging cell
dc.source.beginpagee13302
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


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