A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

Abstract

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes

“…In addition, resveratrol supplementation in non-human primates increased working (as did CR) and spatial memory performance (Dal-Pan et al 2011). Furthermore, this class of compounds was shown to mimic the effects of CR at the transcriptomic levels notably in reducing signs of aging (Barger et al 2008;Pearson et al 2008;Vidal et al 2011). In fact, polyphenols and resveratrol mediate multiple of the previously described pathways such as SIRTs, AMPK and mTOR (Lam et al 2013).…”

“…Other benefits afforded by our signature identification method are robustness to batch effects and to differences in processing methods, and the possibility of using expression data from multiple sources, none of which were relevant for this particular study. We re-analyzed the microarray data produced by Barger et al (2008) on the role of CR and resveratrol at low doses on brain aging. Briefly, 14-monthold male mice fed a control diet were randomly assigned to one of the following: a CR (63 kcal weekly) diet, a resveratrol-supplemented (50 mg resveratrol per kilogram of body weight) control diet and a control diet.…”

Genes regulated by caloric restriction have unique roles within transcriptional networks

“…The upregulation of Nfkbia by CR, in several tissue types (liver, heart, muscle, hypothalamus and lung), could therefore be an important mechanism by which CR inhibits the NF-κB pathway, with consequent effects on lifespan. An alternative possibility is that CR activates Sirt1, which then deacetylases components of the NF-κB complex (Yeung et al, 2004b;Ghosh et al, 2007;Salminen et al, 2008; but see Barger et al, 2008). Previous studies have indeed found that NF-κB signaling is inhibited by caloric restriction in both rodents and humans (Phillips and Leeuwenburgh, 2005;Dirks and Leeuwenburgh, 2006;Weiss et al, 2006;Ugochukwu and Figgers, 2007), and that inhibition of NF-κB blocks the accumulation of beta-amyloid plaques in Alzheimer's mice (Paris et al, 2007), as well as neoplastic transformation of cells during the initial stages of cancer (Karin, 2006).…”

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

“…For example, the decrease in blood glucose caused by short-term fasting in mice is 75% vs the 15% caused by longterm DR or IF (Heilbronn et al, 2005;Holloszy and Fontana, 2007). Similarly, the 75% reduction in blood IGF-I caused by a 2-5-day fast in mice and humans (Clemmons and Underwood, 1991;Lee et al, 2010) is not matched by DR, which causes a 25% IGF-I reduction in mice (Barger et al, 2008) and does not reduce IGF-I levels in humans unless protein intake is also restricted (Fontana et al, 2008). Even together with protein restriction, chronic DR only causes a B30% reduction in IGF-I (Fontana et al, 2008).…”