GenAge entry for SIRT6 (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 239)

HGNC symbol: SIRT6
Aliases
Common name: sirtuin 6

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Description

In yeast, sirtuins regulate epigenetic gene silencing. SIRT6, a chromatin-associated protein, also appears to be involved in DNA repair. SIRT6-null mice are small, with low levels of IGF1, display evidence of genomic instability, and exhibit signs of premature ageing after 2-3 weeks [1590]. One of the roles of SIRT6 appears to be repression of L1 retrotransposons' activity, thus contributing to genome stability. This characteristic however declines over the course of ageing and in response to DNA damage [3634]. Overexpression of SIRT6 increases lifespan by 10-14.5% in mice males, but not in females [1966]. SIRT6 intraarticular injection is protective against chondrocyte degeneration [4347]. In mice overexpressing exogenous SIRT6 (MOSES mice) both lifespan and health span are increased. MOSES mice show improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity. MOSES mice fed on a high fat diet accumulate less fat and show improved glucose tolerance. These mice also show reduced levels of circulating IGF1 [4360].

In humans SIRT6 levels were reduced in the articular chondrocytes of osteoarthritis patients. In chondrocyte cell cultures SIRT6 overexpression supresses replicative senescence, thus inhibiting the inflammatory senescence associated secretory phenotype (SASP). The expression of NFKB1 dependent genes is significantly attenuated by SIRT6 overexpression [4347]. As such, it is possible that SIRT6 plays a role in human ageing and could ameliorate age-related pathologies.

Cytogenetic information

Cytogenetic band: 19p13.3
Location: 4,174,109 bp to 4,182,599 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0003247; post-embryonic cardiac muscle cell growth involved in heart morphogenesis
GO:0006284; base-excision repair
GO:0006471; protein ADP-ribosylation
GO:0008285; negative regulation of cell proliferation
GO:0010569; regulation of double-strand break repair via homologous recombination
GO:0031648; protein destabilization
GO:0031667; response to nutrient levels
GO:0031940; positive regulation of chromatin silencing at telomere
GO:0032206; positive regulation of telomere maintenance
GO:0042593; glucose homeostasis
GO:0045820; negative regulation of glycolytic process
GO:0045892; negative regulation of transcription, DNA-templated
GO:0046325; negative regulation of glucose import
GO:0048146; positive regulation of fibroblast proliferation
GO:0061647; histone H3-K9 modification
GO:1902732; positive regulation of chondrocyte proliferation
GO:1905549; positive regulation of telomeric heterochromatin assembly
GO:1905555; positive regulation blood vessel branching
GO:1905564; positive regulation of vascular endothelial cell proliferation
GO:1990619; histone H3-K9 deacetylation
GO:2000648; positive regulation of stem cell proliferation

Cellular component:

GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005724; nuclear telomeric heterochromatin
GO:0005730; nucleolus
GO:0005737; cytoplasm

Function:

GO:0003682; chromatin binding
GO:0003714; transcription corepressor activity
GO:0003950; NAD+ ADP-ribosyltransferase activity
GO:0003956; NAD(P)+-protein-arginine ADP-ribosyltransferase activity
GO:0005515; protein binding
GO:0008270; zinc ion binding
GO:0017136; NAD-dependent histone deacetylase activity
GO:0034979; NAD-dependent protein deacetylase activity
GO:0046969; NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0070403; NAD+ binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: LMNA, AKT1, EEF2, PRKDC, XRCC5, XRCC6, RELA, HDAC1, MAPK3, EEF1A1, HSPA8, HDAC2, MDM2, STUB1
STRING interaction network

Retrieve sequences for SIRT6

ORF: ORF
CDS: CDS

Homologs in model organisms

Caenorhabditis elegans: sir-2.4
Danio rerio: sirt6
Drosophila melanogaster: Sirt6
Mus musculus: Sirt6
Rattus norvegicus: Sirt6

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Sirt6
A homolog of this gene for Drosophila melanogaster is present as Sirt6

LongevityMap

This gene is present as SIRT6

CellAge

This gene is present as SIRT6