Sirt1

Symbol: Sirt1
Name: sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae)
Entrez gene ID: 93759
Ensembl gene ID: ENSMUSG00000020063
Species: Mouse (Taxid: 10090)

Functional description:
however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transacivation and contributes to its stability. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. SirtT1 75 kDa fragment: catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly (By similarity). [UniProt]

Observation:

Whole-body deletion of Sirt1 in the adulthood results in mice which are seemingly normal in every way. When mice were given low doses of resveratrol after Sirt1 was disabled, there were no discernible improvement in mitochondrial function or any parameter, while mice with normal Sirt1 function given reservatrol showed dramatic increases in energy, mitochondrial biogenesis and function, AMPK activation and increased NAD+ levels in skeletal muscle. When mice lacking Sirt1 were given low doses of reserveratrol, AMPK was unaffected. When doses were significantly increased in these mice, AMPK was activated in a SIRT1-indepent manner, but still no benefit to mitochondrial function resulted [22560220]. Sirt1 overexpression mimicks the effect on reservatrol on mitochondrial function, but failed to extend lifespan [22560220].

SIRT1 knock-out mouse embryonic fibroblasts (MEFs) have a significant greater replicative capacity in culture. p19ARF levels are significantly reduced in SIRT1 knock-out MEFs [16054100].

Sirt1-null mice do not exhibit lifespan extension upon Dietary Restriction [18335035].

Sirt1 is required for high-magnitude circadian transcription of several core clock genes. It deacetylates Per2, Arntl and histones of clock-controlled genes [18662546].

SIRT1 directly [21187328] and indirectly [20450879] prevents telomere shortening.



Interventions:
  • Whole-body Sirt1 deletion in the adulthood
  • Sirt1 overexpression
  • Sirt1 knockout

  • Assays: Replicative Lifespan Organismal Lifespan

    Classification:
  • Aging Associated
  • Clock Modulator
  • DR-Essential
  • DR-Essential Ortholog


  • References:
  • 22560220: SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function.
  • 16054100: Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress.
  • 18662546: SIRT1 regulates circadian clock gene expression through PER2 deacetylation.
  • 20450879: Regulation of SIRT1 in cellular functions: role of polyphenols.
  • 21187328: SIRT1 contributes to telomere maintenance and augments global homologous recombination.
  • 18335035: SirT1 regulates energy metabolism and response to caloric restriction in mice.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • SIRT1 (9606)
  • SIRT1 (9615)
  • SIRT1 (9913)
  • Sirt1 (10090)
  • Sirt1 (10116)
  • SIRT1 (9031)
  • sirt1 (7955)
  • Sir2 (7227)
  • sir-2.1 (6239)

  • Orthologs
  • SIR2 (4932)
  • HST1 (4932)
  • sir-2.1 (6239)
  • Sir2 (7227)
  • SIR2 (4932)
  • HST1 (4932)
  • sir-2.1 (6239)
  • Sir2 (7227)
  • SIR2 (4932)



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