GenAge entry for SIRT1 (Homo sapiens)

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

Gene name (HAGRID: 150)

HGNC symbol
SIRT1 
Aliases
SIR2L1 
Common name
sirtuin 1 

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

SIRT1 is a NAD-dependent deacetylase, which has the ability to regulate a number of processes by deacetylating key proteins, such as TP53 [734]. In yeast, the SIRT1 homologue sir2 has been linked to cellular senescence [200]. Increasing the levels of SIRT1 homologues in fruit flies [1284] and roundworms [199] extends lifespan, although these findings have been questioned by other studies [3321].

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 [201]. Additionally, SIRT1-null mice utilize ingested food inefficiently, are hypermetabolic, contain inefficient liver mitochondria, have elevated rates of lipid oxidation and do not display an extended lifespan under caloric restriction [3608]. 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]. Overall, whole-body moderate overexpression of Sirt1 improves healthy ageing but does not increase mice lifespan [3266]. Brain-specific overexpression in mice results in moderately longer lifespan as females live 16% longer and males 9% longer [3268]. In cockayne syndrome, an accelerated ageing disease, activation of SIRT1 through a high-fat diet and NAD(+) supplementation results in the rescue the mice from the associated progeroid phenotypes [3605]. In murine induced pluripotent stem cells, SIRT1 is necessary for telomere elongation after reprogramming and is required to maintain genomic stability, telomeric transcription and remodeling of telomeric chromatin. SIRT1-deficient induced pluripotent stem cells accumulate chromosomal aberrations and show a derepression of telomeric heterochromatin [3606]. In humans, increased levels of SIRT1 and SIRT3 have been associated with frailty [3607]. Although SIRT1 could impact on age-related diseases, such as type 2 diabetes, further studies are needed to establish its role in human ageing.

Cytogenetic information

Cytogenetic band
10q21.3
Location
67,884,669 bp to 67,918,390 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0000012; single strand break repair
GO:0000122; negative regulation of transcription from RNA polymerase II promoter
GO:0000183; chromatin silencing at rDNA
GO:0000720; pyrimidine dimer repair by nucleotide-excision repair
GO:0000731; DNA synthesis involved in DNA repair
GO:0001525; angiogenesis
GO:0001542; ovulation from ovarian follicle
GO:0001678; cellular glucose homeostasis
GO:0001934; positive regulation of protein phosphorylation
GO:0002821; positive regulation of adaptive immune response
GO:0006260; DNA replication
And 78 more GO terms
Cellular component: GO:0000790; nuclear chromatin
GO:0005634; nucleus
GO:0005635; nuclear envelope
GO:0005637; nuclear inner membrane
GO:0005654; nucleoplasm
GO:0005677; chromatin silencing complex
GO:0005719; nuclear euchromatin
GO:0005720; nuclear heterochromatin
GO:0005730; nucleolus
GO:0005737; cytoplasm
GO:0016605; PML body
And 3 more GO terms
Function: GO:0002039; p53 binding
GO:0003714; transcription corepressor activity
GO:0003950; NAD+ ADP-ribosyltransferase activity
GO:0004407; histone deacetylase activity
GO:0005515; protein binding
GO:0008022; protein C-terminus binding
GO:0017136; NAD-dependent histone deacetylase activity
GO:0019213; deacetylase activity
GO:0033558; protein deacetylase activity
GO:0034979; NAD-dependent protein deacetylase activity
GO:0042393; histone binding
And 8 more GO terms
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
EP300, RICTOR
STRING interaction network
Protein-Protein network diagram for SIRT1

Retrieve sequences for SIRT1

ORF
ORF
CDS
CDS

Homologs in model organisms

Caenorhabditis elegans
sir-2.1
Drosophila melanogaster
Sir2
Danio rerio
sirt1
Mus musculus
Sirt1
Rattus norvegicus
Sirt1

In other databases

GenAge model organism genes
  • A homolog of this gene for Caenorhabditis elegans is present as sir-2.1
  • A homolog of this gene for Drosophila melanogaster is present as Sir2
  • A homolog of this gene for Mus musculus is present as Sirt1
GenDR gene manipulations
  • A homolog of this gene for Drosophila melanogaster is present as Sir2
  • A homolog of this gene for Mus musculus is present as Sirt1
  • A homolog of this gene for Caenorhabditis elegans is present as sir-2.1
LongevityMap
  • This gene is present as SIRT1
CellAge
  • This gene is present as SIRT1

Selected references

External links

EPD
ORF Accession
NM_012238
CDS Accession
NP_036370
OMIM
604479
HPRD
08381
Ensembl
SIRT1
UniProt/Swiss-Prot
SIRT1_HUMAN
GeneCards
SIRT1
Entrez Gene
23411
UniGene
369779
GenAtlas
SIRT1
Internet
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