RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2009-12-01
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| author | Paola Sebastiani Monty Montano Annibale Puca Nadia Solovieff Toshio Kojima Meng C Wang Efthymia Melista Micah Meltzer Sylvia E J Fischer Stacy Andersen Stephen H Hartley Amanda Sedgewick Yasumichi Arai Aviv Bergman Nir Barzilai Dellara F Terry Alberto Riva Chiara Viviani Anselmi Alberto Malovini Aya Kitamoto Motoji Sawabe Tomio Arai Yasuyuki Gondo Martin H Steinberg Nobuyoshi Hirose Gil Atzmon Gary Ruvkun Clinton T Baldwin Thomas T Perls |
| author_facet | Paola Sebastiani Monty Montano Annibale Puca Nadia Solovieff Toshio Kojima Meng C Wang Efthymia Melista Micah Meltzer Sylvia E J Fischer Stacy Andersen Stephen H Hartley Amanda Sedgewick Yasumichi Arai Aviv Bergman Nir Barzilai Dellara F Terry Alberto Riva Chiara Viviani Anselmi Alberto Malovini Aya Kitamoto Motoji Sawabe Tomio Arai Yasuyuki Gondo Martin H Steinberg Nobuyoshi Hirose Gil Atzmon Gary Ruvkun Clinton T Baldwin Thomas T Perls |
| author_sort | Paola Sebastiani |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
| format | Article |
| id | doaj-art-fa7f218462b9403da2649f61a12fb2b8 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fa7f218462b9403da2649f61a12fb2b82025-08-20T02:01:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e821010.1371/journal.pone.0008210RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans.Paola SebastianiMonty MontanoAnnibale PucaNadia SolovieffToshio KojimaMeng C WangEfthymia MelistaMicah MeltzerSylvia E J FischerStacy AndersenStephen H HartleyAmanda SedgewickYasumichi AraiAviv BergmanNir BarzilaiDellara F TerryAlberto RivaChiara Viviani AnselmiAlberto MaloviniAya KitamotoMotoji SawabeTomio AraiYasuyuki GondoMartin H SteinbergNobuyoshi HiroseGil AtzmonGary RuvkunClinton T BaldwinThomas T Perls<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008210&type=printable |
| spellingShingle | Paola Sebastiani Monty Montano Annibale Puca Nadia Solovieff Toshio Kojima Meng C Wang Efthymia Melista Micah Meltzer Sylvia E J Fischer Stacy Andersen Stephen H Hartley Amanda Sedgewick Yasumichi Arai Aviv Bergman Nir Barzilai Dellara F Terry Alberto Riva Chiara Viviani Anselmi Alberto Malovini Aya Kitamoto Motoji Sawabe Tomio Arai Yasuyuki Gondo Martin H Steinberg Nobuyoshi Hirose Gil Atzmon Gary Ruvkun Clinton T Baldwin Thomas T Perls RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. PLoS ONE |
| title | RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. |
| title_full | RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. |
| title_fullStr | RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. |
| title_full_unstemmed | RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. |
| title_short | RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans. |
| title_sort | rna editing genes associated with extreme old age in humans and with lifespan in c elegans |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008210&type=printable |
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