RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans
| Autor: | Joanna Mary Bridger, Paola, Sebastiani, Monty, Montano, Puca, Annibale Alessandro, Nadia, Solovieff, Toshio, Kojima, Wang, Meng C., Efthymia, Melista, Micah, Meltzer, Fischer, Sylvia E. J., Stacy, Andersen, Hartley, Stephen H., Amanda, Sedgewick, Yasumichi, Arai, Aviv, Bergman, Nir, Barzilai, Terry, Dellara F., Alberto, Riva, Chiara Viviani Anselmi, Alberto, Malovini, Aya, Kitamoto, Motoji, Sawabe, Tomio, Arai, Yasuyuki, Gondo, Steinberg, Martin H., Nobuyoshi, Hirose, Gil, Atzmon, Gary, Ruvkun, Baldwin, Clinton T., Perls, Thomas T. |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
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 |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 12, p e8210 (2009) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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