The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet

Sarah J Mitchell; Alejandro Martin-Montalvo; Evi M Mercken; Hector H Palacios; Theresa M Ward; Gelareh Abulwerdi; Robin K Minor; George P Vlasuk; James L Ellis; David A Sinclair; John Dawson; David B Allison; Yongqing Zhang; Kevin G Becker; Michel Bernier; Rafael de Cabo

doi:10.1016/j.celrep.2014.01.031

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet

Cell Rep. 2014 Mar 13;6(5):836-43. doi: 10.1016/j.celrep.2014.01.031. Epub 2014 Feb 27.

Authors

Sarah J Mitchell¹, Alejandro Martin-Montalvo², Evi M Mercken², Hector H Palacios², Theresa M Ward², Gelareh Abulwerdi², Robin K Minor², George P Vlasuk³, James L Ellis³, David A Sinclair⁴, John Dawson⁵, David B Allison⁵, Yongqing Zhang⁶, Kevin G Becker⁶, Michel Bernier², Rafael de Cabo⁷

Affiliations

¹ 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.
² Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
³ Sirtris, a GSK company, 200 Technology Square, Cambridge, MA 02139, USA.
⁴ Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
⁵ School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁶ Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
⁷ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diet
Heterocyclic Compounds, 4 or More Rings / metabolism*
Longevity
Male
Mice
Mice, Inbred C57BL
Sirtuin 1 / genetics
Sirtuin 1 / metabolism*
Survival Analysis
Transcriptome

Substances

Heterocyclic Compounds, 4 or More Rings
SRT1720
Sirtuin 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding