Regulation of Gene Expression through Food-Curcumin as a Sirtuin Activity Modulator.

The sirtuin family comprises NAD-dependent protein lysine deacylases, mammalian sirtuins being either nuclear (SIRT1, SIRT2, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5) or cytosolic enzymes (SIRT2 and SIRT5). They are able to catalyze direct metabolic reactions, thus regulating several physiological functions, such as energy metabolism, stress response, inflammation, cell survival, DNA repair, tissue regeneration, neuronal signaling, and even circadian rhythms. Based on these data, recent research was focused on finding molecules that could regulate sirtuins' expression and/or activity, natural compounds being among the most promising in the field. Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) can induce, through SIRT, modulation of cancer cell senescence, improve endothelial cells protection against atherosclerotic factors, enhance muscle regeneration in atrophy models, and act as a pro-longevity factor counteracting the neurotoxicity of amyloid-beta. Although a plethora of protective effects was reported (antioxidant, anti-inflammatory, anticancer, etc.), its therapeutical use is limited due to its bioavailability issues. However, all the reported effects may be explained via the bioactivation theory, which postulates that curcumin's observed actions are modulated via its metabolites and/or degradation products. The present article is focused on bringing together the literature data correlating the ability of curcumin and its metabolites to modulate SIRT activity and its consequent beneficial effects.