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
Saccharomyces cerevisiae: HST1
Saccharomyces cerevisiae: SIR2

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 Saccharomyces cerevisiae is present as SIR2
A homolog of this gene for Mus musculus is present as Sirt1
A homolog of this gene for Saccharomyces cerevisiae is present as HST1

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
A homolog of this gene for Saccharomyces cerevisiae is present as SIR2
A homolog of this gene for Saccharomyces cerevisiae is present as HST1

CellAge

This gene is present as SIRT1

Studies (8)

Significant/Non-significant: 3/5

Study 1

Longevity Association

Non-significant

Population

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

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

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

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

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: 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

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

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