Sirt6

Symbol: Sirt6
Name: sirtuin 6 (silent mating type information regulation 2, homolog) 6 (S. cerevisiae)
Entrez gene ID: 50721
Ensembl gene ID: ENSMUSG00000034748
Species: Mouse (Taxid: 10090)

Functional description:
NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF- kappa-B target genes. Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate (By similarity). Acts as a corepressor of the transcription factor Hif1a to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. Regulates the production of TNF protein. Has a role in the regulation of life span in male mice, but not in female mice. [UniProt]

Observation:

Sirt6 knockout mice develop signs of premature ageing including a short lifespan [16439206]. Overexpression of Sirt6 in male mice lengthens the median lifespan by 9.9-14.5% and maximum lifespan by 13.1-15.8% [22367546].

Mice without Sirt6 have a higher risk of gastrointestinal cancers. SIRT6 dampens cancer growth by repressing aerobic glycolysis (i.e. conversion of glucose to lactate; a major feature of cancer cells). Loss of Sirt6 increases the number, size and aggressiveness of tumors. Sirt6 loss leads to tumor formation even without activation of oncogenes. Transformed SIRT6-deficient cells exhibit increased glycolysis and tumor growth. Sirt6 inhibits the transcriptional activity of the oncogene Myc via corepression [23217706]. Sirt6 also protects against diet-induced obesity [http://www.biocompare.com/Life-Science-News/127206-Anti-Aging-Gene-Identified-As-Tumor-Suppressor-In-Mice-Research-Finds/].



Interventions:
  • Sirt6 knockout
  • Sirt6 overexpression +9.9 to +14.5% +13.1 to +15.8%

  • Assays: Organismal Lifespan
    Median: +12.2
    Maximum: +14.45

    Classification:
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Positive Aging-Suppressor
  • Cancer-Related
  • Tumor-Suppressor


  • References:
  • 22367546: The sirtuin SIRT6 regulates lifespan in male mice.
  • 23217706: The Histone Deacetylase SIRT6 Is a Tumor Suppressor that Controls Cancer Metabolism.
  • 16439206: Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • SIRT6 (9606)
  • SIRT6 (9598)
  • SIRT6 (9615)
  • SIRT6 (9913)
  • Sirt6 (10090)
  • Sirt6 (10116)
  • SIRT6 (9031)
  • sirt6 (7955)
  • Sirt6 (7227)
  • AgaP_AGAP001458 (7165)
  • SRT1 (3702)
  • Os04g0271000 (4530)

  • Inparanoids
  • ENSMUSP00000048971 (10090)
  • ENSRNOP00000008758 (10116)
  • ENSMUSP00000048971 (10090)
  • ENSMUSP00000048971 (10090)
  • ENSMUSP00000048971 (10090)



  • Edit \ Update (Admin) | Delete

    Comment on This Data Unit