LongevityMap Gene

Gene details

HGNC symbol
SIRT3 
Aliases
SIR2L3 
Common name
sirtuin 3 
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. Two alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]
Cytogenetic Location
11p15.5
UCSC Genome Browser
View 11p15.5 on the UCSC genome browser
OMIM
604481
Ensembl
ENSG00000142082
UniProt/Swiss-Prot
SIR3_HUMAN
Entrez Gene
23410
UniGene
716456
1000 Genomes
1000 Genomes

Homologs in model organisms

Danio rerio
sirt3
Mus musculus
Sirt3
Rattus norvegicus
Sirt3

In other databases

GenAge human genes
  • This gene is present as SIRT3

Studies (7)

Significant/Non-significant: 3/4

Study 1

Longevity Association
Significant
Population
Italian (Southern)
Study Design
G477T exon 3 SNP was examined in 801 unrelated subjects: 331 males and 470 females (120 centenarians: 36 males and 84 females) and controls 18-60 years old
Conclusions
In males the TT genotype increases, while the GT genotype decreases survival in the elderly
Indentifier
G477T
Reference

    Study 2

    Longevity Association
    Significant
    Population
    Italian (Southern)
    Study Design
    A VNTR polymorphism (72-bp repeat core) in intron 5 was analyzed in 945 subjects (312 males and 391 females of 20- to 80-year-old and 242 subjects 90- to 106-year-old, median age 102 years)
    Conclusions
    The VNTR region has an allele specific enhancer activity. The allele completely lacking enhancer activity (allele 2) is virtually absent in males older than 90 years. Age effects were not observed in females.
    Indentifier
    VNTR
    Reference

      Study 3

      Longevity Association
      Non-significant
      Population
      Italian (Northern)
      Study Design
      Three SNPs in the SIRT3 gene were examined in 549 genomic DNA from Treviso Longeva study. A Cross-sectional analysis was carried out by comparing people over and under 85 years of age, followed by a longitudinal analysis considering mortality as the dependent variable.
      Conclusions
      Longitudinal analysis showed no association for rs3825075 in whole cohort and females.
      Indentifier
      rs3825075
      Reference

        Study 4

        Longevity Association
        Non-significant
        Population
        European
        Study Design
        The chromosomal region 11p.15.5 was investigated in 1321 centenarians and 1140 younger subjects from European samples
        Conclusions
        No significant results were observed for genes previously associated with longevity, except for SIRT3. A replication study in a French population did not confirm earlier findings for SIRT3, however. A meta-analysis approach of SIRT3 SNPs did not reveal robust signals.
        Indentifier
        rs511744
        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 (Pā€‰<ā€‰0.05).
          Indentifier
          rs1023430
          Reference

            Study 6

            Longevity Association
            Non-significant
            Population
            Italian (Northern)
            Study Design
            Three SNPs in the SIRT3 gene were examined in 549 genomic DNA from Treviso Longeva study. A Cross-sectional analysis was carried out by comparing people over and under 85 years of age, followed by a longitudinal analysis considering mortality as the dependent variable.
            Conclusions
            Cross-sectional analysis showed SIRT3 was not associated with longevity (but longitudinal analysis showed a possible association; see other entries from same study). SIRT3 genetic variability might be relevant for the modulation of human longevity in the Italian population.
            Indentifier
            rs3825075
            Reference

              Study 7

              Longevity Association
              Significant
              Population
              Italian (Northern)
              Study Design
              Three SNPs in the SIRT3 gene were examined in 549 genomic DNA from Treviso Longeva study. A Cross-sectional analysis was carried out by comparing people over and under 85 years of age, followed by a longitudinal analysis considering mortality as the dependent variable.
              Conclusions
              Longitudinal analysis showed an association for rs4980329, rs11555236 in whole cohort and females (but cross-sectional analysis showed no association; see other entries from the same study). SIRT3 genetic variability might be relevant for the modulation of human longevity in the Italian population.
              Indentifier
              rs4980329
              Reference