LongevityMap Gene

Gene details

HGNC symbol
SIRT1 
Aliases
SIR2; SIR2L1; SIR2alpha 
Common name
sirtuin 1 
Description
This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]
Cytogenetic Location
10q21.3
UCSC Genome Browser
View 10q21.3 on the UCSC genome browser
OMIM
604479
Ensembl
ENSG00000096717
UniProt/Swiss-Prot
A0A024QZQ1_HUMAN
Entrez Gene
23411
UniGene
369779
1000 Genomes
1000 Genomes

Homologs in model organisms

Caenorhabditis elegans
sir-2.1
Danio rerio
sirt1
Drosophila melanogaster
Sir2
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
GenAge human genes
  • This gene 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
CellAge
  • This gene is present as SIRT1

Studies (8)

Significant/Non-significant: 3/5

Study 1

Longevity Association
Non-significant
Population
German
Study Design
Five SNPs, distributed across the entire gene, including the promoter region, were genotyped in 1573 long-lived individuals (centenarians and nonagenarians) and matched younger controls
Conclusions
No evidence for an association was detected between any of the tested SNPs and the longevity phenotype at the allele, genotype or haplotype levels
Indentifier
SIRT1
Reference

    Study 2

    Longevity Association
    Significant
    Population
    American (Caucasian)
    Study Design
    224 nonagenarian cases (84 male, 140 female, 90- 103 y) and 293 young controls (100 male, 193 female, 21- 59 y) from the Louisiana Healthy Aging Study were examined for longevity association study. Then, 170 subjects(25 male, 145 female, ≥98 y) and 220 young controls (84 male, 136 female, 20–59 y) from the Georgia Centenarian Study were examined to replicate the results.
    Conclusions
    rs7896005 in SIRT1 had significant effects on telomere length and was significantly associated with longevity (P < 0.003). rs7896005 association persisted independently of rs132793.
    Indentifier
    rs7896005
    Reference

      Study 3

      Longevity Association
      Significant
      Population
      Dutch
      Study Design
      Associations between variation in SNPs in the SIRT1 gene and human survival were investigated in 1,390 subjects from a general population-based cohort with 18 years of follow-up
      Conclusions
      Carriers of the minor allele of rs12778366 had better glucose tolerance and had a significantly reduced mortality risk compared to the wild types (HR = 0.69).
      Indentifier
      rs12778366
      Reference

        Study 4

        Longevity Association
        Non-significant
        Population
        American of Japanese origin
        Study Design
        Nested-case control study of 5 candidate longevity genes in 8006 Japanese American men from the Honolulu Heart Program and 3741 men part of the Honolulu Asia Aging Study
        Conclusions
        Genetic variants in ADIPOQ, FOXO1A, SIRT1 and COQ7 were not associated with longevity
        Indentifier
        rs7069102
        Reference

          Study 5

          Longevity Association
          Non-significant
          Population
          Danish, German, Dutch
          Study Design
          102 SNPs from 16 longevity candidate genes were examined in Danish. 1089 individuals (ages 92.2-93.8, mean age 93.2, 71.3 female) and 736 middle-aged controls (46-55 y, mean age 50.6, 49.6% female) were involved in this case-control study. Then the results were replicated in a German cohort of 1613 individuals (95-110 y, 73.2% female) and 1104 middle-aged controls (mean age 67.2, SD 4.07, 74.3% female). A 11 years study was introduced in Danish cohort to identify the SNPs associated with longevity, then the results were verified in Dutch longitudinal cohort.
          Conclusions
          After correcting for multiple testing, no SNPs were significantly associated with longevity, except in APOE and CETP. rs4343 (ACE) was nominally significantly associated with longevity (P < 0.05).
          Indentifier
          rs12778366
          Reference

            Study 6

            Longevity Association
            Significant
            Population
            Chinese (Han)
            Study Design
            482 healthy individuals (246 subjects (60 to 91 years old, 71.2 ± 7.1 years; 49.2% male); 236 controls (35 to 59 years old, mean ± SD: 47.3 ± 7.2 years; 45.3% male)) were examined for the association of SIRT1 polymorphisms with healthy aging
            Conclusions
            rs3758391/C and rs4746720/C were more common in case group. Genotype distributions and allele frequencies showed no differences in different genders. The haplotype CC of rs3758391 and rs4746720 was significantly higher in the case group compared to the young control group. The polymorphisms of SIRT1 was associated with healthy aging.
            Indentifier
            rs3758391
            Reference

              Study 7

              Longevity Association
              Non-significant
              Population
              Dutch
              Study Design
              Associations between variation in SNPs in the SIRT1 gene and human survival were investigated in 1,390 subjects from a general population-based cohort with 18 years of follow-up
              Conclusions
              No association with survival was observed for rs7069102 and rs2273773
              Indentifier
              rs7069102
              Reference

                Study 8

                Longevity Association
                Non-significant
                Population
                Ashkenazi Jewish
                Study Design
                A comprehensive resequencing of SIRT1 gene in 16 centenarians and 16 controls identified 36 SNPs (5 of those were novel SNPs). 19 SNPs with MAF > 0.05 were tested in 312 centenarians and 169 controls for association with longevity. 5 tagSNPs from a total 19 SNPs were tested for association with lipid profiles.
                Conclusions
                No association was found between SIRT1 SNPs and longevity, although rs10997854 and rs142194353 were associated with lipid parameters.
                Indentifier
                rs2394443
                Reference