title: Resveratrol improves health and survival of mice on a high-calorie diet.
abstract: Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.
authors.affiliation: Department of Pathology, Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Baur
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Pearson
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Price
authors.forename: Hamish A
authors.initials: HA
authors.lastname: Jamieson
authors.forename: Carles
authors.initials: C
authors.lastname: Lerin
authors.forename: Avash
authors.initials: A
authors.lastname: Kalra
authors.forename: Vinayakumar V
authors.initials: VV
authors.lastname: Prabhu
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Allard
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lopez-Lluch
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Lewis
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pistell
authors.forename: Suresh
authors.initials: S
authors.lastname: Poosala
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Olivier
authors.initials: O
authors.lastname: Boss
authors.forename: Dana
authors.initials: D
authors.lastname: Gwinn
authors.forename: Mingyi
authors.initials: M
authors.lastname: Wang
authors.forename: Sharan
authors.initials: S
authors.lastname: Ramaswamy
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Fishbein
authors.forename: Richard G
authors.initials: RG
authors.lastname: Spencer
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: David
authors.initials: D
authors.lastname: Le Couteur
authors.forename: Reuben J
authors.initials: RJ
authors.lastname: Shaw
authors.forename: Placido
authors.initials: P
authors.lastname: Navas
authors.forename: Pere
authors.initials: P
authors.lastname: Puigserver
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002149:Energy Intake / Q000502:physiology*; D006262:Health; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D020411:Oligonucleotide Array Sequence Analysis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015996:Survival Rate; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; D000263:Adenylate Kinase; D000077185:Resveratrol