Sirtuin activators mimic caloric restriction and delay ageing in metazoans

Abstract

Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity. Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction.

A literature review of flavonoids and lifespan in model organisms

“…We found ten studies on flavonoids and lifespan studies in D. melanogaster. Three of them used single compounds such as the flavanol epicatechin and the flavonol fisetin (58)(59)(60) , the other seven studies were on cocoa powder, green tea extract, Ludwigia octovalvis extract, apple polyphenols, black tea extract (BTE) and BE (61)(62)(63)(64)(65)(66)(67) (Table 2).…”

Nutrition, sirtuins and aging

“…This raises the question of whether activation of sirtuins by STACs is as effective also in vivo where sirtuins probably work under V max conditions. In vivo evidence, however, comes from studies in S. cerevisiae and C. elegans which showed that resveratrol at concentrations of 10 µM in yeast and 100 µM in the nematode extended the life span in dependence on sir2 and sir-2.1, respectively Wood et al, 2004). Another critical point regarding the activation of sirtuins in mammals is the concentration needed to act as STAC since plasma levels of 10 µM or even higher are difficult to achieve.…”

Sirt2‐BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality

“…They have been implicated in diverse biological events, such as aging, energy control, circadian clocks, and mitochondrial biogenesis (Baur, Ungvari, Minor, Le Couteur, & de Cabo, 2012; Preyat & Leo, 2013; Wood et al., 2004). Of them, Sirt2 is associated with mitotic structures, beginning with the centrosome in mitotic prophase, the spindle in metaphase, and the midbody during cytokinesis, presumably to ensure normal cell division (North & Verdin, 2007).…”