Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction

Abstract

Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1-7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms underlying the longevity effect of CR.

The Epigenome and Aging

“…In spite of its role in various cellular processes of high importance, the function of SIRT1 in mammalian longevity is not defi nitive yet (Park et al 2013 ). In one population study, an allele of a SIRT1 SNP was signifi cantly associated with protection against telomere shortening and longevity (Kim et al 2012a ).…”

“…Of the seven, the nuclear SIRT1 has been most extensively studied so far. SIRT1 is involved in various biological pathways, encompassing energy metabolism, regulation of oxidative damage, DNA repair, genome stability, and cell survival (Park et al 2013 ). Regulation of these pathways involves transcriptional modulation of genes by deacetylation of histones near the gene promoters or by direct deacetylation of gene products.…”

Brazilian Society for Food and Nutrition position statement: nutrigenetic tests

“…Adapted from Shankar et al [75] causes activation of the histone deacetylase sirtuin 1 (SIRT1). SIRT1 also induces deacetylation of histone associated to the FOXO1, FOXO3, and FOXO4 genes, which results in modulation of cell cycle, increased defenses against reactive oxygen species, and reduced apoptosis [54].…”

Dietary ALoe vera gel and Microbiota Interactions: Influence of Butyrate and Insulin Sensitivity

“…Intestinal microbiota producing butyrate might be developed for the therapeutic purpose to increase insulin sensitivity in humans with calorie restriction. Park S group [37] described that the numerous studies discussed support a close involvement of Sirt2/ SIRT1 in calorie restriction (CR)-mediated lifespan extension and suggested the possibility that SIRT1 may not be the only factor, but rather one of several components that regulate CR-mediated lifespan extension, as neither overexpression of SIRT1 nor resveratrol extended lifespan in mammals. Guarente L [38] speculated on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow ageing and associated diseases.…”