Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction.

By M. Haigis, L. Guarente. Genes & Development, 2006

1,338 citations recorded by the source corpus.

Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in yeast, worms and flies. Mammals contain seven homologs of yeast Sir2, SIRT1-7. Here, we review recent findings demonstrating the role of these mammalian sirtuins as regulators of physiology, calorie restriction, and aging. The current findings sharpen our understanding of sirtuins as potential pharmacological targets to treat the major diseases of aging.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/68d7f188b8078d9ad458cba39ef08ec106f7b23f

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Citations in the corpus

Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice (2008, positive): “…many nonhistone proteins that are involved in cell growth, apoptosis, neuronal protection, adaptation to caloric restriction, organ metabolism and function, cellular senescence, and tumorigenesis (Baur et al., 2006; Haigis and Guarente, 2006; Saunders and Verdin, 2007; Vaquero et al., 2007).”
Mammalian Sir2 Homolog SIRT3 Regulates Global Mitochondrial Lysine Acetylation (2007, background): “Conserved from bacteria to humans, the sirtuin family of NAD -dependent protein deacetylase/mono-ADP-ribosyltransferase enzymes controls a variety of cellular processes such as aging, metabolism, and gene silencing (18, 24).”
Regulation of mitochondrial biogenesis (2010, background): “Their absence of lifespan extension has been interpreted as evidence that SIRT1 is required for the caloric restriction response [67].”
Acetylation of tau inhibits its degradation and contributes to tauopathy. (2010, positive): “The activities of HDACs in classes I and II (HADC1–11) depend on zinc as a cofactor; the activities of class III HDACs (sirtuins) depend on the relative levels of NAD and NADH (Haigis and Guarente, 2006; Michan and Sinclair, 2007).”
SIRT3 is a Mitochondrial Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism During Stress (2010, background): “The mammalian sirtuin family consists of seven NAD+-dependent protein deacetylases that are localized to the nucleus (SIRT1, SIRT6, and SIRT7), mitochondria (SIRT3, SIRT4, and SIRT5), and cytoplasm (SIRT2), respectively, and that regulate a wide range of intracellular process (Haigis and Guarente, 2”
Sirt1 and the Mitochondria (2016, background): “In yeast, Sir2p regulates chromatin silencing, and reduces the accumulation of rDNA circles during yeast replicative aging (Sinclair and Guarente, 1997).”
SirT1 gain-of-function increases energy efficiency and prevents diabetes in mice (2008, positive): “Genetic screens in lower organisms provide evidence that gain-of-function of the deacetylase Sir2 results in beneficial metabolic effects and life span extension (Haigis and Guarente, 2006).”
A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy (2008, background): “As opposed to these relatively simple organisms, mammalian species have seven different sirtuin family members (8, 9).”
The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men (2008, background): “In 2000, the Sir2 (silent information regulator-2) or sirtuin (Sir2-like protein) family of NAD + -dependent deacetylases was discovere”
The Histone Deacetylase SIRT6 Regulates Glucose Homeostasis via Hif1α (2010, neutral): “In yeast, the founding member of the sirtuin family, Sir2, was originally discovered as a silencing factor, functioning as a sensor of the metabolic activity of the cell to influence gene transcription, DNA repair, recombination, and life span (Haigis and Guarente, 2006; Longo and Kennedy, 2006).”
SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle (2009, positive): “SIRT3 and 4 have NAD-dependent deacetylase and ADP-ribosyl transferase activities, respectively, and have been shown to play roles in mitochondrial metabolism (Haigis and Guarente, 2006).”
Lysine Propionylation and Butyrylation Are Novel Post-translational Modifications in Histones*S (2007, background): “In addition to their roles in fundamental biology, lysine acetylation and its regulatory enzymes (acetyltransferases and deacetylases) are intimately linked to aging (11) and several major diseases such as cancer, neurodegenerative disorders, and cardiovascular diseases (12–14).”
miR-34a repression of SIRT1 regulates apoptosis (2008, background): “SIRT1 is an NAD-dependent deacetylase that regulates apoptosis in response to oxidative and genotoxic stress (45, 46).”
Neural mechanisms of ageing and cognitive decline (2010, background): “Caloric restriction and sirtuins Caloric restriction — that is, the reduction of calorie intake without causing malnutrition — is the only known intervention that robustly increases lifespan in many specie”
Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. (2008, background): “…debate (Chen and Guarente, 2007; Kaeberlein and Powers, 2007; Longo and Kennedy, 2006; Michan and Sinclair, 2007), it is well established that the sirtuins- a family of evolutionarily conserved deacetylases - play important roles in numerous physiological processes (Haigis and Guarente, 2006).”
A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis (2008, background): “A number of Sirt1 protein deacetylase substrates have been previously identified including p53 and the Foxo family of transcription factors (5).”