title: The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet.
abstract: The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice.
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA; Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW 2065, Australia; Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Mitchell
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Montalvo
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Hector H
authors.initials: HH
authors.lastname: Palacios
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Ward
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Abulwerdi
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Robin K
authors.initials: RK
authors.lastname: Minor
authors.affiliation: Sirtris, a GSK company, 200 Technology Square, Cambridge, MA 02139, USA.
authors.forename: George P
authors.initials: GP
authors.lastname: Vlasuk
authors.affiliation: Sirtris, a GSK company, 200 Technology Square, Cambridge, MA 02139, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Ellis
authors.affiliation: Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: John
authors.initials: J
authors.lastname: Dawson
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.affiliation: Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA. Electronic address: decabora@grc.nia.nih.gov.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
mesh_terms: D000818:Animals; D004032:Diet; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism*; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D059467:Transcriptome
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C525422:SRT1720; D056564:Sirtuin 1