LongevityMap Gene

Gene details

HGNC symbol: PPARGC1A
Aliases: LEM6; PGC1; PGC1A; PGC-1v; PPARGC1; PGC-1alpha; PGC-1(alpha)
Common name: PPARG coactivator 1 alpha
Description: The protein encoded by this gene is a transcriptional coactivator that regulates the genes involved in energy metabolism. This protein interacts with PPARgamma, which permits the interaction of this protein with multiple transcription factors. This protein can interact with, and regulate the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity. [provided by RefSeq, Jul 2008]
Cytogenetic Location: 4p15.2
UCSC Genome Browser: View 4p15.2 on the UCSC genome browser
OMIM: 604517
Ensembl: ENSG00000109819
UniProt/Swiss-Prot: A0A024R9Q9_HUMAN
Entrez Gene: 10891
UniGene: 527078
1000 Genomes: 1000 Genomes

Homologs in model organisms

Danio rerio: ppargc1a
Drosophila melanogaster: srl
Mus musculus: Ppargc1a
Rattus norvegicus: Ppargc1a

In other databases

GenAge model organism genes

A homolog of this gene for Drosophila melanogaster is present as Spargel

GenAge human genes

This gene is present as PPARGC1A

GenAge microarray genes

This gene is present as PPARGC1A

CellAge

This gene is present as PPARGC1A

Studies (5)

Significant/Non-significant: 1/4

Study 1

Longevity Association

Non-significant

Population

Study Design

2 exonic polymorphisms were examined in 122 semisupercentenarians (older than 105, 107 female, 15 male, mean age 106.8 years) and 122 healthy younger controls (105 female, 17 male, mean age 33.33)

Conclusions

No significant differences relative to longevity were found

Indentifier

Reference

Study 2

Longevity Association: Non-significant
Population: Caucasians
Study Design: Meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955).
Conclusions: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached significance after correcting for multiple testing
Indentifier

Study 3

Longevity Association

Population

Study Design

1,018 SNPs within a 10-kb window around 40 mTOR signalling genes were studied for differences in variation between 417 unrelated nonagenarian participants and 476 younger controls

Conclusions

As a whole, there was a significant association of genetic variation in the mTOR pathway and familial longevity, though no individual gene was significant after correcting for multiple hypothesis testing

Indentifier

Reference

Study 4

Longevity Association: Non-significant
Population: Spanish
Study Design: The association between five common polymorphisms in genes of this pathway and extreme longevity were examined using a case (107 centenarian, 100–111 years, 89 female)-control (284 young adults, ≤50 years, 150 female) design
Conclusions: The studied genetic variants of the PPARD-PPARGC1A-NRF-TFAM pathway were not associated with extreme longevity. A marginal association could exist for rs1937 in TFAM (p=0.003).
Indentifier

Study 5

Longevity Association: Non-significant
Population: Italian (Southern)
Study Design: A two-stage case-control study was performed to identify the association between longevity and variation of in homeostasis regulation pathway genes. 317 SNPs in 104 genes were analyzed in 78 cases (≥90 years, median age 98 years, 42 females) and 71 controls (<90 years, median age 67 years, 32 females) in stage 1. Then, 31 candidate SNPs identified in stage 1 (π markers = 0.1) were analyzed in an independent sample composed by 288 cases (≥90 years, median age 92 years, 163 females) and 554 controls (<90 years, median age 67 years, 277 females).
Conclusions: After adjustment for multiple testing, no significant association was identified between various SNPs and longevity.
Indentifier