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An epigenetic biomarker of aging for lifespan and healthspan.
Levine, Morgan E; Lu, Ake T; Quach, Austin; Chen, Brian H; Assimes, Themistocles L; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A; Stewart, James D; Li, Yun; Whitsel, Eric A; Wilson, James G; Reiner, Alex P; Aviv, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi; Horvath, Steve.
Afiliación
  • Levine ME; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Lu AT; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Quach A; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Chen BH; Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD 21224, USA.
  • Assimes TL; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Bandinelli S; Geriatric Unit, Azienda Toscana Centro, Florence, Italy.
  • Hou L; Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
  • Baccarelli AA; Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.
  • Stewart JD; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Li Y; Department of Genetics, Department of Biostatistics, Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Whitsel EA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Wilson JG; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Reiner AP; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Aviv A; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Lohman K; Center of Human Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
  • Liu Y; Center of Human Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
  • Ferrucci L; Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forrest School of Medicine, Winston-Salem, NC 27157, USA.
  • Horvath S; Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD 21224, USA.
Aging (Albany NY) ; 10(4): 573-591, 2018 04 18.
Article en En | MEDLINE | ID: mdl-29676998
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Biomarcadores / Epigénesis Genética / Longevidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Biomarcadores / Epigénesis Genética / Longevidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Aging (Albany NY) Asunto de la revista: GERIATRIA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
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