| Description | SIRT1 is a NAD-dependent deacetylase, which has the ability to regulate a number of processes by deacetylating key proteins, such as TP53 [0734]. In yeast, the SIRT1 homologue sir2 has been linked to cellular senescence [0200]. Increasing the levels of SIRT1 homologues in fruit flies [1284] and roundworms [0199] extends lifespan.
SIRT1-null mice are born smaller than controls with evidence of developmental retardation. Depending on their genetic background, SIRT1-null mice either die shortly after birth or reach adulthood, the latter being smaller than controls and sterile [0201]. Heterozygous mice had a normal average lifespan [1922]. SIRT1 is overexpressed in calorie restricted rats, a response attenuated by insulin (INS) and IGF1 [1328]. Increased dosage of SIRT1 in pancreatic beta cells enhanced INS secretion [1481]. Mice with moderate overexpression of SIRT1 exhibit fat mass gain similar to controls exposed to a high-fat diet [1897]. Cardiac-specific low to moderate overexpression of SIRT1 attenuated age-dependent increases in cardiac hypertrophy, apoptosis, and expression of senescent biomarkers while a high level of overexpression had detrimental effects and induced cardiomyopathy [1930]. Although SIRT1 could impact on age-related diseases, such as type 2 diabetes, further studies are needed to establish its role in human ageing. |
[1897] Pfluger et al. (2008), Sirt1 protects against high-fat diet-induced metabolic damage, PubMed
[1922] Li et al. (2008), SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons, PubMed
[1896] Li et al. (2008), Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation, PubMed
[1850] Gates et al. (2007), Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease, PubMed
[1901] Sun et al. (2007), SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B, PubMed
[1898] Bordone et al. (2007), SIRT1 transgenic mice show phenotypes resembling calorie restriction, PubMed
[1921] Kim et al. (2007), SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis, PubMed
[1930] Alcendor et al. (2007), Sirt1 regulates aging and resistance to oxidative stress in the heart, PubMed
[1846] Gerhart-Hines et al. (2007), Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha, PubMed
[1935] Hida et al. (2007), Strong expression of a longevity-related protein, SIRT1, in Bowen's disease, PubMed
[1894] Sommer et al. (2006), DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse, PubMed
[1810] Sasaki et al. (2006), Progressive loss of SIRT1 with cell cycle withdrawal, PubMed
[1936] Fu et al. (2006), Hormonal control of androgen receptor function through SIRT1, PubMed
[1804] Wang et al. (2006), Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage, PubMed
[1801] Longo and Kennedy (2006), Sirtuins in aging and age-related disease, PubMed
[1818] Sauve et al. (2006), The biochemistry of sirtuins, PubMed
[1776] Qin et al. (2006), Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer's disease amyloid neuropathology by calorie restriction, PubMed
[1770] Kolthur-Seetharam et al. (2006), Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage, PubMed
[1808] Pruitt et al. (2006), Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation, PubMed
[1601] Jeon et al. (2006), MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance, PubMed
[1586] Kamel et al. (2006), SirT1 fails to affect p53-mediated biological functions, PubMed
[1616] Bordone et al. (2006), Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells, PubMed
[1566] Flachsbart et al. (2006), Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity, PubMed
[1558] Anekonda and Reddy (2006), Neuronal protection by sirtuins in Alzheimer's disease, PubMed
[1653] Ota et al. (2006), Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells, PubMed
[1570] Kaeberlein et al. (2005), Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients, PubMed
[1583] Greer and Brunet (2005), FOXO transcription factors at the interface between longevity and tumor suppression, PubMed
[1806] Ford et al. (2005), Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival, PubMed
[1564] Fabrizio et al. (2005), Sir2 blocks extreme life-span extension, PubMed
[1582] Chen et al. (2005), Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses, PubMed
[1769] Pillai et al. (2005), Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity, PubMed
[1574] Chen et al. (2005), SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling, PubMed
[1481] Moynihan et al. (2005), Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice, PubMed
[1575] Michishita et al. (2005), Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins, PubMed
[1480] Chua et al. (2005), Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress, PubMed
[1547] Guarente (2005), Calorie restriction and SIR2 genes--towards a mechanism, PubMed
[1300] Rodgers et al. (2005), Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1, PubMed
[0173] Nemoto et al. (2004), Nutrient availability regulates SIRT1 through a forkhead-dependent pathway, PubMed
[1284] Rogina and Helfand (2004), Sir2 mediates longevity in the fly through a pathway related to calorie restriction, PubMed
[1578] Araki et al. (2004), Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration, PubMed
[1285] Wood et al. (2004), Sirtuin activators mimic caloric restriction and delay ageing in metazoans, PubMed
[1095] Daitoku et al. (2004), Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity, PubMed
[1328] Cohen et al. (2004), Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase, PubMed
[1068] Blander and Guarente (2004), The sir2 family of protein deacetylases, PubMed
[1138] Picard et al. (2004), Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma, PubMed
[1805] Yeung et al. (2004), Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase, PubMed
[1071] Motta et al. (2004), Mammalian SIRT1 represses forkhead transcription factors, PubMed
[0990] Brunet et al. (2004), Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase, PubMed
[0980] Cheng et al. (2003), Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice, PubMed
[1710] Fulco et al. (2003), Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state, PubMed
[0201] McBurney et al. (2003), The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis, PubMed
[0177] Newman et al. (2002), A Drosophila homologue of Sir2 modifies position-effect variegation but does not affect life span, PubMed
[0202] Rogina et al. (2002), Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction, PubMed
[1425] Hoopes et al. (2002), Mutations in DNA replication genes reduce yeast life span, PubMed
[0734] Langley et al. (2002), Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence, PubMed
[0735] Vaziri et al. (2001), hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase, PubMed
[1070] Luo et al. (2001), Negative control of p53 by Sir2alpha promotes cell survival under stress, PubMed
[0199] Tissenbaum and Guarente (2001), Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans, PubMed
[0200] Kaeberlein et al. (1999), The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms, PubMed
[1493] Tsukamoto et al. (1997), Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae, PubMed
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