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DNA methylation-based measures of biological age: meta-analysis predicting time to death
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Aging | doi:10.18632/aging.101020. Brian H. Chen, Riccardo E. Marioni, Elena Colicino, Marjolein J. Peters, Cavin K. Ward-Caviness, Pei-Chien Tsai, Nicholas S. Roetker, Allan C. Just, Ellen W. Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R. Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P. Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L. Lunetta, Joanne M. Murabito, Stefania Bandinelli, Dena G. Hernandez, David Melzer, Michael Nalls, Luke C. Pilling, Timothy R. Price, Andrew B. Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M. Visscher, Sonia Shah, Naomi R. Wray, Allan F. McRae, Oscar H. Franco, Albert Hofman, André G. Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E. Levine, Ake T. Lu, Philip S. Tsao, Lifang Hou, JoAnn E. Manson, Cara L. Carty, Andrea Z. LaCroix, Alexander P. Reiner, Tim D. Spector, Andrew P. Feinberg, Daniel Levy, Andrea Baccarelli, Joyce van Meurs, Jordana T. Bell, Annette Peters, Ian J. Deary, James S. Pankow, Luigi Ferrucci, Steve Horvath
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“These clocks were highly accurate in predicting the chronological age of new samples and also showed some capacity for predicting differences in mortality risk, although effect sizes tend to be small and inconsistent across studies56–58.”
From Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial (2023) · cites this paper as [58]
Experimental — accuracy not yet measuredIn the citing paper
“These hypotheses have been supported by observations that individuals with positive age gaps, termed age acceleration, are at greater risk of mortality and some diseases of ageing such as heart disease, metabolic syndrome and certain cancers46–50.”
From Measuring biological age using omics data (2022) · cites this paper as [46]
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“However, mortality risk, which is widely used as a measure of ‘global’ biological age, has shown an overall weak and variable association with these clocks46,58, which raises questions as to what biology they actually measure.”
From Measuring biological age using omics data (2022) · cites this paper as [46]
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DNA methylation dynamics in aging: how far are we from understanding the mechanisms?
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Simpson, D. J., & Chandra, T. (2021) · Aging Cell · doi:10.1111/acel.13452 · Cited by 195
Roetker, N. S., Pankow, J. S., Bressler, J., Morrison, A. C., & Boerwinkle, E. (2018) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.117.001937 · Cited by 181
Self-citationRyan, J. L., Wrigglesworth, J., Loong, J., Fransquet, P., & Woods, R. L. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz099 · Cited by 178
DNA methylation predicts age and provides insight into exceptional longevity of bats
Wilkinson, G. S., Adams, D. M., Haghani, A., Lu, A. T.-H., Zoller, J. A., Breeze, C. E., Arnold, B. D., Ball, H. C., Carter, G. G., Cooper, L. N., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21900-2 · Cited by 175
Self-citationBiT age: A transcriptome‐based aging clock near the theoretical limit of accuracy
Meyer, D. H., & Schumacher, B. (2021) · Aging Cell · doi:10.1111/acel.13320 · Cited by 165
DNA methylation-based age clocks: From age prediction to age reversion
Noroozi, R., Ghafouri‐Fard, S., Pisarek, A., Rudnicka, J., Spólnicka, M., Branicki, W., Taheri, M. N., & Pośpiech, E. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101314 · Cited by 171
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Self-citationCell‐free DNA as a biomarker of aging
Teo, Y. V., Capri, M., Morsiani, C., Pizza, G., Faria, A. M. C., Franceschi, C., & Neretti, N. (2019) · Aging Cell · doi:10.1111/acel.12890 · Cited by 127
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Self-citationGensous, N., Garagnani, P., Santoro, A., Giuliani, C., Ostan, R., Fabbri, C., Milazzo, M., Gentilini, D., Blasio, A. M. D., Pietruszka, B., et al. (2020) · GeroScience · doi:10.1007/s11357-019-00149-0 · Cited by 153
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DNA Methylation Clocks and Their Predictive Capacity for Aging Phenotypes and Healthspan
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Self-citationAn epigenetic predictor of death captures multi-modal measures of brain health
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Self-citationAdversity exposure during sensitive periods predicts accelerated epigenetic aging in children
Marini, S., Davis, K. A., Soare, T. W., Zhu, Y., Suderman, M. J., Simpkin, A. J., Smith, A. D. A. C., Wolf, E. J., Relton, C. L., & Dunn, E. C. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.104484 · Cited by 145
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Systematic underestimation of the epigenetic clock and age acceleration in older subjects
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“Epigenetic clocks”: Theory and applications in human biology
Ryan, C. P. (2020) · American Journal of Human Biology · doi:10.1002/ajhb.23488 · Cited by 138
Kim, S., Myers, L., Wyckoff, J., Cherry, K. E., & Jazwinski, S. M. (2017) · GeroScience · doi:10.1007/s11357-017-9960-3 · Cited by 136
Clonal hematopoiesis associated with epigenetic aging and clinical outcomes
Nachun, D. C., Lu, A. T.-H., Bick, A. G., Natarajan, P., Weinstock, J. S., Szeto, M. D., Kathiresan, S., Abecasis, G. R., Taylor, K. D., Guo, X., et al. (2021) · Aging Cell · doi:10.1111/acel.13366 · Cited by 136
Self-citationMolecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification
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Marioni, R. E., Suderman, M. J., Chen, B. H., Horvath, S., Bandinelli, S., Morris, T. J., Beck, S., Ferrucci, L., Pedersen, N. L., Relton, C. L., et al. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly060 · Cited by 127
Self-citationA meta-analysis of genome-wide association studies of epigenetic age acceleration
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Self-citationEstrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study
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Self-citationMitochondrial metabolism and DNA methylation: a review of the interaction between two genomes
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Cellular reprogramming and epigenetic rejuvenation
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An integrative study of five biological clocks in somatic and mental health
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Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock
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Metadata
- Authors
- Chen, B. H., Marioni, R. E., Colicino, E., Peters, M. J., Ward-Caviness, C. K., Tsai, P.-C., Roetker, N. S., Just, A. C., Demerath, E. W., Guan, W., Bressler, J., Fornage, M., Studenski, S., Vandiver, A. R., Moore, A. Z., Tanaka, T., Kiel, D. P., Liang, L., Vokonas, P., Schwartz, J., Lunetta, K. L., Murabito, J. M., Bandinelli, S., Hernandez, D. G., Melzer, D., Nalls, M., Pilling, L. C., Price, T. R., Singleton, A. B., Gieger, C., Holle, R., Kretschmer, A., Kronenberg, F., Kunze, S., Linseisen, J., Meisinger, C., Rathmann, W., Waldenberger, M., Visscher, P. M., Shah, S., Wray, N. R., McRae, A. F., Franco, O. H., Hofman, A., Uitterlinden, A. G., Absher, D., Assimes, T., Levine, M. E., Lu, A. T., Tsao, P. S., Hou, L., Manson, J. E., Carty, C. L., LaCroix, A. Z., Reiner, A. P., Spector, T. D., Feinberg, A. P., Levy, D., Baccarelli, A., van Meurs, J., Bell, J. T., Peters, A., Deary, I. J., Pankow, J. S., Ferrucci, L., & Horvath, S.
- Affiliations
- National Institutes of Health (US)
- The University of Queensland (AU)
- Columbia University (US)
- Erasmus MC (NL)
- Helmholtz Munich (DE)
- King's College London (GB)
- University of Minnesota (US)
- The University of Texas Health Science Center at Houston (US)
- Baylor College of Medicine (US)
- Johns Hopkins University (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Boston University (US)
- Geriatric Unit, Usl Centro Toscana Florence, Italy
- University of Exeter (GB)
- Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA
- Innsbruck Medical University (AT)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Institute of Epidemiology II, Helmholtz Zentrum München, 85764 Neuherberg, Germany
- Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
- HudsonAlpha Institute for Biotechnology (US)
- University of California, Los Angeles (US)
- VA Palo Alto Health Care System (US)
- Northwestern University (US)
- Children's National (US)
- University of California San Diego (US)
- University of Washington (US)
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, ; USA
- Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, 3000 CA, The Netherlands
- Corresponding author
- Horvath, Steve
- ORCID
- Chen, Brian H.
- Marioni, Riccardo E.
- Colicino, Elena
- Peters, Marjolein J.
- Ward-Caviness, Cavin K.
- Tsai, Pei-Chien
- Roetker, Nicholas S.
- Just, Allan C.
- Demerath, Ellen W.
- Guan, Weihua
- Bressler, Jan
- Fornage, Myriam
- Studenski, Stephanie
- Vandiver, Amy R.
- Moore, Ann Zenobia
- Tanaka, Toshiko
- Kiel, Douglas P.
- Liang, Liming
- Vokonas, Pantel
- Schwartz, Joel
- Lunetta, Kathryn L.
- Murabito, Joanne M.
- Bandinelli, Stefania
- Hernandez, Dena G.
- Melzer, David
- Pilling, Luke C.
- Singleton, Andrew B.
- Gieger, Christian
- Holle, Rolf
- Kronenberg, Florian
- Kunze, Sonja
- Linseisen, Jakob
- Rathmann, Wolfgang
- Visscher, Peter M.
- Shah, Sonia
- Wray, Naomi R.
- McRae, Allan F.
- Franco, Oscar H.
- Uitterlinden, André G.
- Absher, Devin
- Assimes, Themistocles
- Levine, Morgan E.
- Lu, Ake T.
- Tsao, Philip S.
- Hou, Lifang
- Manson, JoAnn E.
- Carty, Cara L.
- LaCroix, Andrea Z.
- Spector, Tim D.
- Feinberg, Andrew P.
- Levy, Daniel
- Baccarelli, Andrea
- Bell, Jordana T.
- Peters, Annette
- Deary, Ian J.
- Pankow, James S.
- Ferrucci, Luigi
- Horvath, Steve
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-09-28
- Volume
- 8
- Issue
- 9
- Pages
- 1844-1865
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5076441
- OpenAlex
- W2421283105
- Cited by
- 1,126
- References
- 39
- Citations by year
- 2026: 82 · 2025: 107 · 2024: 132 · 2023: 103 · 2022: 141 · 2021: 153 · 2020: 117 · 2019: 114 · 2018: 97 · 2017: 74 · 2016: 4
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- OPUS (Augsburg University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health and Human Services (HHSN268201100002C, HHSN2682011 00003C, 5RC2HL102419, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C, HHSN 268201100001C, HHSN268201500001I, HHSN268201100046C, HHSN268201100004C, HHSN-271-2011-00004C)
- U.S. Department of Veterans Affairs
- Brigham and Women's Hospital
- Ohio State University
- Wake Forest University
- University of Pittsburgh
- Wellcome Trust (FP7/2007–2013)
- Scottish Government
- National Institute for Health and Care Research (FP7/2007–2013, NF-SI-0507-10228, NF-SI-0514-10027)
- Age UK (MR/K026992/1)
- King's College London
- European Commission (2007–2013, FP7 2007-2013, FP7/2007, 305280)
- University of Edinburgh (MR/K026992/1)
- German-Israeli Foundation for Scientific Research and Development
- University of Queensland
- ZonMw
- Bundesministerium für Bildung und Forschung
- Erasmus Medisch Centrum (014-93-015)
- Bundesministerium für Gesundheit
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (FP7 2007-2013, 911-03-012, 175.010.2005.011, 917103521)
- Centre for Cognitive Ageing and Cognitive Epidemiology (MR/K026992/1)
- National Institutes of Health (HHSN268201100012C, FP7/2007-2013, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,HHSN268201100004C, and HHSN271201100004C, HHSN268201100008C, HHSN268201100006C, HHSN268201100004C, HHSN26820- 1100005C, HHSN268201100007C, HHSN268201100046C, HHSN271201100004C, HHSN268201100011C, HHSN268201100001C, HHSN268201100010C, HHSN268201100002C, n01hc25195-41-0-1, HHSN268201100009C, HHSN268201100003C, HHSN268201500001I, N01-HC 25195)
- Directorate for Biological Sciences
- University at Buffalo
- Medical Research Council (MR/K026992/1, MR/M013111/1)
- Biotechnology and Biological Sciences Research Council (MR/K026992/1)
- Economic and Social Research Council (ES/N000404/1)
- Helmholtz Zentrum München
- Münchner Zentrum für Gesundheitswissenschaften
- National Institute on Aging (HHSN-271-2011-00004C,, R01AG029451, N01-HC-25195, R01AG042187, U34AG051425, RF1AG036042, R01AG042511)
- National Heart, Lung, and Blood Institute (HHSN268201 100012C, HHSN268201100007I, HHSN268201100007C, HHSN2682 01100008C, HH-SN-268201100006C, HHSN268201100011C, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C, HHSN2682011-00005I, HHSN2682011-00001I, HHSN2682011-00002I, N01‐HC25195, HHSN268201100004C, HHSN268201500001I, HHSN2682011-00009I, HHSN268201100005C, HHSN268201500001C, HHSN268201100005G, HHSN268201100010C, HHSN271201100004C, HHSN2682011‐00004I, HHSN26820-1100002C, HHSN268201100011I, N01-HC-025195, 60442456, HHSN268201100046C, HHSN26820 1100009C, HHSN268201100001C, HHSN2682011-00008I, HHSN268201100003C, RC2HL102419)
- National Institute of General Medical Sciences (T32GM007309)
- National Institute of Environmental Health Sciences (R00ES023450, R01ES025225, R01ES021733, R01ES015172, P30ES023515)
- Center for Information Technology
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DNA methylation, biological age, epigenetic clocks, time to death, mortality prediction, mortality risk
- MeSH terms
- Aging, Female, Humans, Male, Mortality, Risk Factors, Logistic Models, Survival Analysis, T-Lymphocyte Subsets, DNA Methylation, Epigenesis, Genetic, Racial Groups
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