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FLASH GENE
Symbol SIRT1 contributors: mct/shn - updated : 24-07-2016
HGNC name sirtuin 1
HGNC id 14929
ASSOCIATED DISORDERS
corresponding disease(s)
Other morbid association(s)
TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
constitutional     --over  
by various biological stresses, including caloric restriction, which has been shown to prevent numerous diseases of aging such as Alzheimer's
constitutional       gain of function
decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells
constitutional     --over  
might extend lifespan by decreasing fat storage
constitutional     --over  
in the vasculature during blood vessel growth, where it controls the angiogenic activity of endothelial cells
constitutional     --low  
precisely during human embryonic stem cell differentiation at both mRNA and protein levels
constitutional     --low  
promotes activation of the oncogenic AKT pathway to mediate XPC down-regulation
tumoral     --over  
overexpressed in hepatocellular carcinomas (HCC) cell lines and in a subset of HCC
constitutional       loss of function
its activity is reduced in liver and adipose tissue in response to obesity
tumoral     --over  
with overexpression of KIAA1967 is associated with poor prognosis of gastric carcinoma
Susceptibility
  • to obesity in men
  • to ventricular septal defects (VSD)
  • to Parkinson disease (PD)
  • Variant & Polymorphism other
  • genetic variation in SIRT1 increases the risk for obesity, and SIRT1 genotype correlates with visceral obesity parameters in obese men
  • variants within the SIRT1 gene promoter identified in VSD patients may alter the transcriptional activities of SIRT1 gene promoter
  • genetic variants within the SIRT1 gene promoter may repress SIRT1 gene expression, contributing to PD
  • Candidate gene manipulation of Sirt1 can be a plausible therapeutic target molecule in the treatment of renal tubular damages
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    SIRT1 inhibition by nicotinamide reduces proliferation of granulosa tumor cells (both OGCT-derived cell lines and primary explanted OGCT cells) by increasing the amount/activity of endogenous FOXL2, which provides a therapeutic lead
    neurologyneurodegenerative 
    promising avenue for therapeutic intervention in neurodegenerative disorders
    neurologyneurodegenerativealzheimer
    therapeutic potential of resveratrol and other sirtuin-activating compounds in Alzheimer disease
    cancer  
    inhibitors for SIRT1 may have anticancer potential,(impaired activation of Ras-MAPK pathway might take part in a senescence-like growth arrest program induced by Sirtinol, with attenuated Ras-MAPK signaling in cancer cells)
    diabete  
    therapeutics targeting of SIRT1 might provide novel approaches to the treatment of endocrine-related clinical conditions such as obesity, insulin resistance syndromes, and diabetes
    osteoarticular  
    up-regulation of Sirt-1 appears to be an important consequence of resveratrol on tenocytes and may be useful in the development of future therapies for the treatment of tendinitis
    immunologyautoimmune 
    possible therapeutic use of SIRT1 inhibitors against autoimmunity
    ANIMAL & CELL MODELS
  • SIRT1 is not only induced in mouse models of neurodegeneration but also in primary cultured neurons under neurotoxic stresses
  • Sir2-alpha null mice smaller at birth and died during the early postnatal period
  • Disruption of Sirt1 expression in zebrafish and mice resulted in defective blood vessel formation and blunted ischemia-induced neovascularization
  • Sirt1-deficient mice are reported to exhibit severe neural defects, including exencephaly and disturbed neuroretinal morphogenesis
  • Sirt1 knockdown in mIMCD3 cells enhanced alpha-ENaC mRNA levels and alpha-ENaC promoter activity, and inhibited global H3K79 methylation, particularly H3K79 trimethylation, in chromatin associated with the alpha-ENaC promoter
  • mouse embryo fibroblasts lacking SIRT1 contain reduced PML protein levels (