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SIRT1-independent epigenetic effects of resveratrol mediated through the estrogen receptor

Lookup NU author(s): Dr Luisa WakelingORCiD, Fatema AlAtawi, Laura Ions, Professor John Hesketh, Professor Dianne Ford

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Abstract

We aimed to determine if epigenetic effects could be a component of the mechanism through which the dietary polyphenol resveratrol brings about its reported beneficial effects on healthspan and if such effects are though activation of SIRT1, the histone deacetylase purported to play a role in lifespan extension resulting from dietary restriction (DR). Resveratrol reduced histone expression in human intestinal Caco-2 cells through an effect on histone gene expression (opposing an aging-related observed increase in mouse intestine) and increased DNA methylation. The ER antagonist fulvestrant abrogated the effect on histone expression. SIRT1 overexpression alone had no effect on histone expression or DNA methylation but overexpression abrogated both effects of resveratrol. Genes with altered expression resulting from resveratrol treatment or SIRT1 knockdown did not overlap but both sets of genes showed an overlap greater than expected by chance with genes affected by DR. The findings indicate that resveratrol has epigenetic effects that are mediated through the ER and are independent of SIRT1 and that such actions may contribute to effects of resveratrol to increase healthspan.


Publication metadata

Author(s): Alatawi F; Ions LJ; Ford D; Wakeling LA; Hesketh J

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Experimental Biology Meeting

Year of Conference: 2012

Pages: 716.4-716.4

ISSN: 0892-6638

Publisher: Federation of American Societies for Experimental Biology

URL: http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/716.4?sid=7b918a19-722e-4d4d-8bd3-117ec089232c

Library holdings: Search Newcastle University Library for this item

Series Title: FASEB Journal

ISBN: 15306860


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