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
Saccharomyces cerevisiae: HST2

In other databases

GenAge model organism genes

A homolog of this gene for Saccharomyces cerevisiae is present as HST2

GenAge human genes

This gene is present as SIRT3

GenDR gene manipulations

A homolog of this gene for Saccharomyces cerevisiae is present as HST2

Studies (7)

Significant/Non-significant: 3/4

Study 1

Longevity Association

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

Reference

Study 2

Longevity Association

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

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

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

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

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

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