SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

Evi M. Mercken; Sarah J. Mitchell; Alejandro Martin-Montalvo; Robin K. Minor; Maria Almeida; Ana P. Gomes; Morten Scheibye-Knudsen; Hector H. Palacios; Jordan J. Licata; Yongqing Zhang; Kevin G. Becker; Husam Khraiwesh; José A. González-Reyes; José M. Villalba; Joseph A. Baur; Peter Elliott; Christoph Westphal; George P. Vlasuk; James L. Ellis; David A. Sinclair; Michel Bernier; Rafael de Cabo

doi:10.1111/acel.12220

SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

Evi M. Mercken, Sarah J. Mitchell, Alejandro Martin-Montalvo, Robin K. Minor, Maria Almeida, Ana P. Gomes, Morten Scheibye-Knudsen, Hector H. Palacios, Jordan J. Licata, Yongqing Zhang, Kevin G. Becker, Husam Khraiwesh, José A. González-Reyes, José M. Villalba, Joseph A. Baur, Peter Elliott, Christoph Westphal, George P. Vlasuk, James L. Ellis, David A. SinclairMichel Bernier, Rafael de Cabo^*

^*Corresponding author for this work

139 Citations (Scopus)

Abstract

Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.

Original language	English
Journal	Aging Cell
Volume	13
Issue number	5
Pages (from-to)	787-796
Number of pages	10
ISSN	1474-9718
DOIs	https://doi.org/10.1111/acel.12220
Publication status	Published - 1 Oct 2014
Externally published	Yes

Keywords

Healthspan
Inflammation
Lifespan
Muscle wasting
Osteoporosis
Sirtuins

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10.1111/acel.12220Licence: CC BY

acel.12220Final published version, 1.06 MBLicence: CC BY

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Mercken, E. M., Mitchell, S. J., Martin-Montalvo, A., Minor, R. K., Almeida, M., Gomes, A. P., Scheibye-Knudsen, M., Palacios, H. H., Licata, J. J., Zhang, Y., Becker, K. G., Khraiwesh, H., González-Reyes, J. A., Villalba, J. M., Baur, J. A., Elliott, P., Westphal, C., Vlasuk, G. P., Ellis, J. L., ... de Cabo, R. (2014). SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell, 13(5), 787-796. https://doi.org/10.1111/acel.12220

Mercken, EM, Mitchell, SJ, Martin-Montalvo, A, Minor, RK, Almeida, M, Gomes, AP, Scheibye-Knudsen, M, Palacios, HH, Licata, JJ, Zhang, Y, Becker, KG, Khraiwesh, H, González-Reyes, JA, Villalba, JM, Baur, JA, Elliott, P, Westphal, C, Vlasuk, GP, Ellis, JL, Sinclair, DA, Bernier, M & de Cabo, R 2014, 'SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass', Aging Cell, vol. 13, no. 5, pp. 787-796. https://doi.org/10.1111/acel.12220

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abstract = "Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.",

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AU - Becker, Kevin G.

AU - Khraiwesh, Husam

AU - González-Reyes, José A.

AU - Villalba, José M.

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AU - Westphal, Christoph

AU - Vlasuk, George P.

AU - Ellis, James L.

AU - Sinclair, David A.

AU - Bernier, Michel

AU - de Cabo, Rafael

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SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

Abstract

Keywords

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