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RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 12, p e8210 (2009)
- Publication Year :
- 2009
- Publisher :
- Public Library of Science, 2009.
-
Abstract
- Background The strong familiality of living to extreme ages suggests that human longevity is genetically regulated. The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered. Methodology/Principal Findings Here, we first show that 18 single nucleotide polymorphisms (SNPs) in the RNA editing genes ADARB1 and ADARB2 are associated with extreme old age in a U.S. based study of centenarians, the New England Centenarian Study. We describe replications of these findings in three independently conducted centenarian studies with different genetic backgrounds (Italian, Ashkenazi Jewish and Japanese) that collectively support an association of ADARB1 and ADARB2 with longevity. Some SNPs in ADARB2 replicate consistently in the four populations and suggest a strong effect that is independent of the different genetic backgrounds and environments. To evaluate the functional association of these genes with lifespan, we demonstrate that inactivation of their orthologues adr-1 and adr-2 in C. elegans reduces median survival by 50%. We further demonstrate that inactivation of the argonaute gene, rde-1, a critical regulator of RNA interference, completely restores lifespan to normal levels in the context of adr-1 and adr-2 loss of function. Conclusions/Significance Our results suggest that RNA editors may be an important regulator of aging in humans and that, when evaluated in C. elegans, this pathway may interact with the RNA interference machinery to regulate lifespan.
- Subjects :
- Adult
Male
Adolescent
Genotype
Adenosine Deaminase
Longevity
Genetics and Genomics/Nuclear Structure and Function
lcsh:Medicine
Biology
Genomic databases
Polymorphism, Single Nucleotide
Linkage Disequilibrium
03 medical and health sciences
Young Adult
0302 clinical medicine
Gene Frequency
Odds Ratio
Animals
Humans
lcsh:Science
Caenorhabditis elegans
Gene
Genetics and Genomics/Genetics of Disease
Genes, Helminth
030304 developmental biology
Aged
Genetics
Aged, 80 and over
0303 health sciences
Multidisciplinary
Chromosomes, Human, Pair 10
lcsh:R
RNA-Binding Proteins
Reproducibility of Results
Middle Aged
Genetics and Genomics/Gene Function
RNA editing
Christian ministry
lcsh:Q
Female
RNA Editing
030217 neurology & neurosurgery
Algorithms
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....8a3023feb72398d242971a016ce04662