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Article: Haploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice

TitleHaploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice
Authors
Issue Date2018
PublishereLife Sciences Publications Ltd. The Journal's web site is located at http://elifesciences.org/
Citation
eLife, 2018, v. 7, p. e32127 How to Cite?
AbstractMammalian sirtuin 6 (Sirt6) is a conserved NAD+-dependent deacylase and mono-ADP ribosylase that is known to be involved in DNA damage repair, metabolic homeostasis, inflammation, tumorigenesis, and aging. Loss of Sirt6 in mice results in accelerated aging and premature death within a month. Here, we show that haploinsufficiency (i.e., heterozygous deletion) of Trp53 dramatically extends the lifespan of both female and male Sirt6-deficient mice. Haploinsufficiency of Trp53 in Sirt6-deficient mice rescues several age-related phenotypes of Sirt6-deficient mice, including reduced body size and weight, lordokyphosis, colitis, premature senescence, apoptosis, and bone marrow stem cell decline. Mechanistically, SIRT6 deacetylates p53 at lysine 381 to negatively regulate the stability and activity of p53. These findings establish that elevated p53 activity contributes significantly to accelerated aging in Sirt6-deficient mice. Our study demonstrates that p53 is a substrate of SIRT6, and highlights the importance of SIRT6-p53 axis in the regulation of aging.
Persistent Identifierhttp://hdl.handle.net/10722/263886
ISSN
2017 Impact Factor: 7.616
2015 SCImago Journal Rankings: 6.356

 

DC FieldValueLanguage
dc.contributor.authorGHOSH, S-
dc.contributor.authorWONG, SKK-
dc.contributor.authorJIANG, Z-
dc.contributor.authorLiu, B-
dc.contributor.authorWang, Y-
dc.contributor.authorHao, Q-
dc.contributor.authorGorbunova, V-
dc.contributor.authorLIU, X-
dc.contributor.authorZhou, Z-
dc.date.accessioned2018-10-22T07:46:01Z-
dc.date.available2018-10-22T07:46:01Z-
dc.date.issued2018-
dc.identifier.citationeLife, 2018, v. 7, p. e32127-
dc.identifier.issn2050-084X-
dc.identifier.urihttp://hdl.handle.net/10722/263886-
dc.description.abstractMammalian sirtuin 6 (Sirt6) is a conserved NAD+-dependent deacylase and mono-ADP ribosylase that is known to be involved in DNA damage repair, metabolic homeostasis, inflammation, tumorigenesis, and aging. Loss of Sirt6 in mice results in accelerated aging and premature death within a month. Here, we show that haploinsufficiency (i.e., heterozygous deletion) of Trp53 dramatically extends the lifespan of both female and male Sirt6-deficient mice. Haploinsufficiency of Trp53 in Sirt6-deficient mice rescues several age-related phenotypes of Sirt6-deficient mice, including reduced body size and weight, lordokyphosis, colitis, premature senescence, apoptosis, and bone marrow stem cell decline. Mechanistically, SIRT6 deacetylates p53 at lysine 381 to negatively regulate the stability and activity of p53. These findings establish that elevated p53 activity contributes significantly to accelerated aging in Sirt6-deficient mice. Our study demonstrates that p53 is a substrate of SIRT6, and highlights the importance of SIRT6-p53 axis in the regulation of aging.-
dc.languageeng-
dc.publishereLife Sciences Publications Ltd. The Journal's web site is located at http://elifesciences.org/-
dc.relation.ispartofeLife-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleHaploinsufficiency of Trp53 dramatically extends the lifespan of Sirt6-deficient mice-
dc.typeArticle-
dc.identifier.emailHao, Q: qhao@hku.hk-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.authorityWang, Y=rp02093-
dc.identifier.authorityHao, Q=rp01332-
dc.identifier.authorityZhou, Z=rp00503-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7554/eLife.32127-
dc.identifier.hkuros295418-
dc.identifier.volume7-
dc.identifier.spagee32127-
dc.identifier.epagee32127-
dc.publisher.placeCambridge, UK-

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