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

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

Author information

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.

PMID:
24582957
PMCID:
PMC4010117
DOI:
10.1016/j.celrep.2014.01.031
[Indexed for MEDLINE]
Free PMC Article

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