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 af dette arbejde

139 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Aging Cell
Vol/bind	13
Udgave nummer	5
Sider (fra-til)	787-796
Antal sider	10
ISSN	1474-9718
DOI	https://doi.org/10.1111/acel.12220
Status	Udgivet - 1 okt. 2014
Udgivet eksternt	Ja

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10.1111/acel.12220Licens: CC BY

acel.12220Forlagets udgivne version, 1,06 MBLicens: 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, bind 13, nr. 5, s. 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 - Almeida, Maria

AU - Gomes, Ana P.

AU - Scheibye-Knudsen, Morten

AU - Palacios, Hector H.

AU - Licata, Jordan J.

AU - Zhang, Yongqing

AU - Becker, Kevin G.

AU - Khraiwesh, Husam

AU - González-Reyes, José A.

AU - Villalba, José M.

AU - Baur, Joseph A.

AU - Elliott, Peter

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

Abstract

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