Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/48981
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dc.contributor.authorMarcon, Francescait
dc.contributor.authorMeschini, Robertait
dc.contributor.authorIorio, Egidioit
dc.contributor.authorPalleschi, Simonettait
dc.contributor.authorDe Luca, Gabrieleit
dc.contributor.authorSiniscalchi, Esterit
dc.contributor.authorConti, Luigiit
dc.contributor.authorChirico, Matteait
dc.contributor.authorPisanu, Maria Elenait
dc.contributor.authorDe Battistis, Francescait
dc.contributor.authorRossi, Barbarait
dc.contributor.authorMinoprio, Annait
dc.contributor.authorGiuliani, Alessandroit
dc.contributor.authorKarran, Peterit
dc.contributor.authorBignami, Margheritait
dc.date.accessioned2023-01-30T17:46:18Z-
dc.date.available2023-01-30T17:46:18Z-
dc.date.issued2022it
dc.identifier.issn1474-9726it
dc.identifier.urihttp://hdl.handle.net/2067/48981-
dc.description.abstracthMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.it
dc.language.isoengit
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleYoung transgenic hMTH1 mice are protected against dietary fat-induced metabolic stress—implications for enhanced longevityit
dc.typearticle*
dc.identifier.doi10.1111/acel.13605it
dc.identifier.pmid35670027it
dc.identifier.scopus2-s2.0-85131313088it
dc.identifier.urlhttps://api.elsevier.com/content/abstract/scopus_id/85131313088it
dc.relation.journalAGING CELLit
dc.relation.articlee13605it
dc.relation.volume21it
dc.relation.issue7it
dc.type.miur262*
item.fulltextWith Fulltext-
item.openairetypearticle-
item.cerifentitytypePublications-
item.grantfulltextrestricted-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.journal.journalissn1474-9726-
crisitem.journal.anceE222488-
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