Show simple item record

dc.contributor.authorXu, Caiyue
dc.contributor.authorWang, Lu
dc.contributor.authorFozouni, Parinaz
dc.contributor.authorEvjen, Gry
dc.contributor.authorChandra, Vemika
dc.contributor.authorJiang, Jing
dc.contributor.authorLu, Congcong
dc.contributor.authorNicastri, Michael
dc.contributor.authorBretz, Corey
dc.contributor.authorWinkler, Jeffrey D.
dc.contributor.authorAmaravadi, Ravi
dc.contributor.authorGarcia, Benjamin A.
dc.contributor.authorAdams, Peter D.
dc.contributor.authorOtt, Melanie
dc.contributor.authorTong, Wei
dc.contributor.authorJohansen, Terje
dc.contributor.authorDou, Zhixun
dc.contributor.authorBerger, Shelley L.
dc.date.accessioned2023-04-27T07:33:55Z
dc.date.available2023-04-27T07:33:55Z
dc.date.issued2020-09-28
dc.description.abstractSIRT1 (Sir2) is an NAD<sup>+</sup>-dependent deacetylase that plays critical roles in a broad range of biological events, including metabolism, the immune response and ageing<sup>1,2,3,4,5</sup>. Although there is strong interest in stimulating SIRT1 catalytic activity, the homeostasis of SIRT1 at the protein level is poorly understood. Here we report that macroautophagy (hereafter referred to as autophagy), a catabolic membrane trafficking pathway that degrades cellular components through autophagosomes and lysosomes, mediates the downregulation of mammalian SIRT1 protein during senescence and in vivo ageing. In senescence, nuclear SIRT1 is recognized as an autophagy substrate and is subjected to cytoplasmic autophagosome–lysosome degradation, via the autophagy protein LC3. Importantly, the autophagy–lysosome pathway contributes to the loss of SIRT1 during ageing of several tissues related to the immune and haematopoietic system in mice, including the spleen, thymus, and haematopoietic stem and progenitor cells, as well as in CD8<sup>+</sup>CD28<sup>-</sup> T cells from aged human donors. Our study reveals a mechanism in the regulation of the protein homeostasis of SIRT1 and suggests a potential strategy to stabilize SIRT1 to promote productive ageing.en_US
dc.identifier.citationXu, Wang, Fozouni, Evjen, Chandra, Jiang, Lu, Nicastri, Bretz, Winkler, Amaravadi, Garcia, Adams, Ott, Tong, Johansen, Dou, Berger. SIRT1 is downregulated by autophagy in senescence and ageing. Nature Cell Biology. 2020en_US
dc.identifier.cristinIDFRIDAID 1893571
dc.identifier.doi10.1038/s41556-020-00579-5
dc.identifier.issn1465-7392
dc.identifier.issn1476-4679
dc.identifier.urihttps://hdl.handle.net/10037/29076
dc.language.isoengen_US
dc.publisherNature Researchen_US
dc.relation.journalNature Cell Biology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleSIRT1 is downregulated by autophagy in senescence and ageingen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


File(s) in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)