Journal article
RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C-elegans
PloS one, v 4(12), pp e8210-e8210
14 Dec 2009
PMID: 20011587
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C-elegans
- Creators
- Paola Sebastiani - Boston UniversityMonty Montano - Boston UniversityAnnibale Puca - MultiMedicaNadia Solovieff - Boston UniversityToshio Kojima - RIKEN Advanced Science InstituteMeng C. Wang - Massachusetts General HospitalEfthymia Melista - Boston UniversityMicah Meltzer - Boston UniversitySylvia E. J. Fischer - Massachusetts General HospitalStacy Andersen - Boston UniversityStephen H. Hartley - Boston UniversityAmanda Sedgewick - Boston UniversityYasumichi Arai - Keio UniversityAviv Bergman - Albert Einstein College of MedicineNir Barzilai - Albert Einstein College of MedicineDellara F. Terry - Boston UniversityAlberto Riva - University of FloridaChiara Viviani Anselmi - MultiMedicaAlberto Malovini - MultiMedicaAya Kitamoto - RIKEN Advanced Science InstituteMotoji Sawabe - Tokyo Metropolitan Geriatric HospitalTomio Arai - Tokyo Metropolitan Geriatric HospitalYasuyuki Gondo - Osaka University of Human SciencesMartin H. Steinberg - Boston UniversityNobuyoshi Hirose - Keio UniversityGil Atzmon - Albert Einstein College of MedicineGary Ruvkun - Massachusetts General HospitalClinton T. Baldwin - Boston UniversityThomas T. Perls - Boston University
- Publication Details
- PloS one, v 4(12), pp e8210-e8210
- Publisher
- Public Library Science
- Number of pages
- 14
- Grant note
- R01HL087681 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HL087681; K24 AG025727; R01 AR055115; RO1 AG027216 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA M01RR012248 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) Italian Ministry of Research and University; Ministry of Education, Universities and Research (MIUR) MGH ECOR Fund K24AG025727 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) AG-027734; AG-18728; RR-12248; DK-20541; M01-RR12248 / Glenn Foundation Life Sciences Research Foundation R01AR055115 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) P30DK020541 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Health Sciences
- Web of Science ID
- WOS:000272830300005
- Scopus ID
- 2-s2.0-77949520652
- Other Identifier
- 991021866822304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity