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PMID: 29676998 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

An epigenetic biomarker of aging for lifespan and healthspan.

Aging ·Vol. 10 ·No. 4 ·2018-00-18 ·Pages 573-591

Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S, Hou L, Baccarelli AA, Stewart JD, Li Y, Whitsel EA, Wilson JG, Reiner AP, Aviv A, Lohman K, Liu Y, Ferrucci L, Horvath S

Abstract

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.

Keywords
epigenetic clock DNA methylation biomarker healthspan
MeSH Terms
Aging/genetics Biomarkers/analysis Epigenesis, Genetic/genetics Humans Longevity/genetics,physiology
Chemicals
Biomarkers
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Levine Morgan E
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Lu Ake T
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Quach Austin
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Chen Brian H
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD 21224, USA.
Assimes Themistocles L
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bandinelli Stefania
Geriatric Unit, Azienda Toscana Centro, Florence, Italy.
Hou Lifang
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 Andrea A
Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, USA.
Stewart James D
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Li Yun
Department of Genetics, Department of Biostatistics, Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599, USA.
Whitsel Eric A
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA. | Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Wilson James G
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Reiner Alex P
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Aviv Abraham
Center of Human Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
Lohman Kurt
Center of Human Development and Aging, New Jersey Medical School, Rutgers State University of New Jersey, Newark, NJ 07103, USA.
Liu Yongmei
Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forrest School of Medicine, Winston-Salem, NC 27157, USA.
Ferrucci Luigi
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, USA, Baltimore, MD 21224, USA.
Horvath Steve
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. | Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.
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Article Info
Journal
Aging
Abbr.
Aging (Albany NY)
ISSN
1945-4589
DOI
10.18632/aging.101414
Published
2018-00-18
Pages
573-591
Language
English
Region
United States
NLM ID
101508617
PMCID
PMC5940111
Grants
NIMHD NIH HHS · R01 MD009164 · United States
NHLBI NIH HHS · HHSN268201100046C · United States
NHLBI NIH HHS · HHSN268201300049C · United States
NIA NIH HHS · P30 AG010161 · United States
NIA NIH HHS · HHSN271201100004C · United States
NHLBI NIH HHS · HHSN268201500001I · United States
NIA NIH HHS · RF1 AG054474 · United States
NHLBI NIH HHS · N01HC25195 · United States
NHLBI NIH HHS · HHSN268201300046C · United States
NHLBI NIH HHS · HHSN268201100002I · United States
NIA NIH HHS · U34 AG051425 · United States
NIDDK NIH HHS · R01 DK103531 · United States
NHLBI NIH HHS · HHSN268201100001I · United States
NIA NIH HHS · RF1 AG036042 · United States
NIA NIH HHS · K99 AG052604 · United States
NHLBI NIH HHS · R01 HL135009 · United States
NHLBI NIH HHS · R01 HL116446 · United States
NIEHS NIH HHS · R01 ES020836 · United States
NHLBI NIH HHS · HHSN268201500001C · United States
NHLBI NIH HHS · HHSN268201100004I · United States
NHLBI NIH HHS · HHSN268201300048C · United States
WHI NIH HHS · HHSN268201100003C · United States
NHLBI NIH HHS · R01 HL101250 · United States
NHLBI NIH HHS · HHSN268201300050C · United States
WHI NIH HHS · HHSN268201100002C · United States
NHLBI NIH HHS · HHSN268201300047C · United States
NIGMS NIH HHS · U54 GM115428 · United States
WHI NIH HHS · HHSN268201100001C · United States
WHI NIH HHS · HHSN268201100004C · United States
NIA NIH HHS · R01 AG015819 · United States
External Links
PubMed source DOI: 10.18632/aging.101414 PMC Full Text View journal details
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