The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet

(A) Kaplan-Meier survival curves for mice fed either a standard diet (SD) or high-fat diet (HFD)

supplemented without or with SRT1720 (SDSRT1720, HFD-SRT1720). 

Blue is a standard diet. Red is a standard diet plus SRT1720. Purple is a high-fat diet. Orange is a high-fat diet plus SRT1720.

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Cell Reports, 27 February 2014
Copyright © 2014 The Authors
10.1016/j.celrep.2014.01.031 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Authors
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 Cabosend emailSee Affiliations

Highlights
SRT1720 supplementation extends mean lifespan of mice fed a standard diet
SRT1720 improves healthspan of mice fed a standard diet
SRT1720 reduces the age-associated increase in risk factors for metabolic disease
SRT1720 supplementation confers antiinflammatory properties in target tissues

Summary
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.