Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm-Reference-Cited by-同舟云学术

Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

Published:2020-05-05 Issue: Volume:9 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

Belsky Daniel W¹²^ORCID,Caspi Avshalom³⁴⁵⁶,Arseneault Louise³,Baccarelli Andrea⁷,Corcoran David L⁶,Gao Xu⁷,Hannon Eiliss⁸,Harrington Hona Lee⁴,Rasmussen Line JH⁴⁹^ORCID,Houts Renate⁴,Huffman Kim¹⁰¹¹,Kraus William E¹⁰¹¹,Kwon Dayoon²,Mill Jonathan⁸,Pieper Carl F¹¹¹²,Prinz Joseph A⁶,Poulton Richie¹³,Schwartz Joel¹⁴,Sugden Karen⁴,Vokonas Pantel¹⁵,Williams Benjamin S⁴,Moffitt Terrie E³⁴⁵⁶

Affiliation:

1. Department of Epidemiology, Columbia University Mailman School of Public Health, New York, United States

2. Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, United States

3. Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, United Kingdom

4. Department of Psychology and Neuroscience, Duke University, Durham, United States

5. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, United States

6. Center for Genomic and Computational Biology, Duke University, Durham, United States

7. Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, United States

8. University of Exeter Medical School, College of Medicine and Health, Exeter, United Kingdom

9. Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark

10. Duke Molecular Physiology Institute, Duke University, Durham, United States

11. Duke University Center for the Study of Aging, Duke University, Durham, United States

12. Department of Biostatistics, Duke University School of Medicine, Durham, United States

13. Department of Psychology and Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Otago, New Zealand

14. Department of Environmental Health Sciences, Harvard TH Chan School of Public Health, Boston, United States

15. Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, United States

Abstract

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging.

Funder

Medical Research Council

National Institute on Aging

National Institute of Child Health and Development

CIFAR

Jacobs Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Link

https://cdn.elifesciences.org/articles/54870/elife-54870-v3.pdf

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