Mammalian Sirt1: insights on its biological functions

Abstract

Sirt1 (member of the sirtuin family) is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from various proteins. Sirt1 performs a wide variety of functions in biological systems. The current review focuses on the biological functions of Sirt1 in obesity-associated metabolic diseases, cancer, adipose tissue, aging, cellular senescence, cardiac aging and stress, prion-mediated neurodegeneration, inflammatory signaling in response to environmental stress, development and placental cell survival.

Anti-tumor effects and cellular mechanisms of resveratrol

“…SIRT1 can mediate cellular metabolism and energy production through regulation of forkhead box protein O1 (FOXO1) activity and insulin sensitivity and modulate inflammatory responses through NF-κB or cell growth through inhibition of mTOR activity. Besides, SIRT1 can also protect cells from apoptosis in response to genotoxic stress (54)(55)(56)(57)(58). In contrast, there are some data which indicate that SIRT1 possesses significant tumor suppressor activity.…”

Pharmacologic Inhibition of Cardiac Stem Cell Senescence

“…Although aging has been associated with stem cell senescence and dysfunction, the molecular mechanisms through which Sirt1 could protect primitive cells have not been completely delineated yet. However, the most prominent ones are: the positive regulation of telomeric length (Palacios, et al, 2010), the reduction of ROS production, the inhibition of p53 (Rahman and Islam, 2011) and the induction of autophagy (Lee, et al, 2008). In this regard, Resveratrol is emerging as a potent drug able to delay age-related deteriorations and in mediating cardio-protection, conceivably by activating Sirt1 .…”

“…Mammalians, in fact, possess at least 7 sirtuins, that act as metabolic sensors directly linking environmental signals to metabolic homeostasis and www.intechopen.com stress response. Sirt1, the most studied mammalian Sirtuin, controls gene expression, metabolism and aging, through a continuously growing list of substrates, that include: p53, members of the FoxO family, HES1 (hairy and enhancer of split 1), HEY2 (hairy/enhancerof-split related with YRPW motif 2), PPAR (peroxisome proliferator-activated receptor gamma), p300, PGC-1 (PPAR coactivator), and NF-κB (nuclear factor kappaB) (Rahman and Islam, 2011). Although aging has been associated with stem cell senescence and dysfunction, the molecular mechanisms through which Sirt1 could protect primitive cells have not been completely delineated yet.…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…SIRT1 and HIF-1 are reciprocally regulated so that in the hypoxic\inflammatory setting HIF- is activated while Sirt1 is decreased due to NAD + scarcity so inhibiting HIF-deacetylation and inactivation while in normoxic environment HIF-is inactivated by oxygen-dependent prolyl hydroxylases PHD2 activated by SIRT1. Sirtuins are class III NAD + -dependant histone deacetylases (HDAC) targeting histones, transcription factors and enzymes regulating in this way gene expression and metabolic function in relation to the energy status of the cell [60][61][62][63][64]. They have been related to the regulation of metabolism, apoptosis and inflammation, to extending life span and to the healthy aging.…”