SRT1720 improves survival and healthspan of obese mice

被引：0

作者：

Robin K. Minor

Joseph A. Baur

Ana P. Gomes

Theresa M. Ward

Anna Csiszar

Evi M. Mercken

Kotb Abdelmohsen

Yu-Kyong Shin

Carles Canto

Morten Scheibye-Knudsen

Melissa Krawczyk

Pablo M. Irusta

Alejandro Martín-Montalvo

Basil P. Hubbard

Yongqing Zhang

Elin Lehrmann

Alexa A. White

Nathan L. Price

William R. Swindell

Kevin J. Pearson

Kevin G. Becker

Vilhelm A. Bohr

Myriam Gorospe

Josephine M. Egan

Mark I. Talan

Johan Auwerx

Christoph H. Westphal

James L. Ellis

Zoltan Ungvari

George P. Vlasuk

Peter J. Elliott

David A. Sinclair

Rafael de Cabo

机构：

[1] Laboratory of Experimental Gerontology,Department of Physiology

[2] National Institute on Aging,Department of Pathology

[3] National Institutes of Health,Department of Geriatric Medicine

[4] Institute for Diabetes,Department of Human Science

[5] Obesity and Metabolism,Department of Genetics

[6] University of Pennsylvania School of Medicine,undefined

[7] Paul F. Glenn Laboratories for the Biological Mechanism of Aging,undefined

[8] Harvard Medical School,undefined

[9] Reynolds Oklahoma Center on Aging,undefined

[10] University of Oklahoma Health Sciences Center,undefined

[11] Laboratory of Cellular and Molecular Biology,undefined

[12] National Institute on Aging,undefined

[13] National Institutes of Health,undefined

[14] Laboratory of Clinical Investigation,undefined

[15] National Institute on Aging,undefined

[16] National Institutes of Health,undefined

[17] Laboratory of Integrative and Systems Physiology (LISP),undefined

[18] Ecole Polytechnique Fédérale de Lausanne (EPFL),undefined

[19] Laboratory of Molecular Gerontology,undefined

[20] National Institute on Aging,undefined

[21] National Institutes of Health,undefined

[22] Laboratory of Cardiovascular Sciences,undefined

[23] National Institute on Aging,undefined

[24] National Institutes of Health,undefined

[25] Georgetown University Medical Center,undefined

[26] Gene Expression and Genomics Unit,undefined

[27] National Institute on Aging,undefined

[28] National Institutes of Health,undefined

[29] Harvard Medical School,undefined

[30] Graduate Center for Nutritional Sciences,undefined

[31] University of Kentucky,undefined

[32] Sirtris,undefined

[33] a GSK Company,undefined

来源：

Scientific Reports | / 1卷

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摘要：

Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.

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