title: SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass.
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.
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Mercken
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Mitchell
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin-Montalvo
authors.forename: Robin K
authors.initials: RK
authors.lastname: Minor
authors.forename: Maria
authors.initials: M
authors.lastname: Almeida
authors.forename: Ana P
authors.initials: AP
authors.lastname: Gomes
authors.forename: Morten
authors.initials: M
authors.lastname: Scheibye-Knudsen
authors.forename: Hector H
authors.initials: HH
authors.lastname: Palacios
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Licata
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Husam
authors.initials: H
authors.lastname: Khraiwesh
authors.forename: José A
authors.initials: JA
authors.lastname: González-Reyes
authors.forename: José M
authors.initials: JM
authors.lastname: Villalba
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Baur
authors.forename: Peter
authors.initials: P
authors.lastname: Elliott
authors.forename: Christoph
authors.initials: C
authors.lastname: Westphal
authors.forename: George P
authors.initials: GP
authors.lastname: Vlasuk
authors.forename: James L
authors.initials: JL
authors.lastname: Ellis
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
mesh_terms: D000375:Aging; D000818:Animals; D001823:Body Composition; D015992:Body Mass Index; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis
chemical_list: D006574:Heterocyclic Compounds, 2-Ring; C584666:SRT2104
keywords: healthspan; inflammation; lifespan; muscle wasting; osteoporosis; sirtuins