DunedinPACE, a DNA methylation biomarker of the pace of aging
Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al....
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/73420 |
| _version_ | 1797998344300134400 |
|---|---|
| author | Daniel W Belsky Avshalom Caspi David L Corcoran Karen Sugden Richie Poulton Louise Arseneault Andrea Baccarelli Kartik Chamarti Xu Gao Eilis Hannon Hona Lee Harrington Renate Houts Meeraj Kothari Dayoon Kwon Jonathan Mill Joel Schwartz Pantel Vokonas Cuicui Wang Benjamin S Williams Terrie E Moffitt |
| author_facet | Daniel W Belsky Avshalom Caspi David L Corcoran Karen Sugden Richie Poulton Louise Arseneault Andrea Baccarelli Kartik Chamarti Xu Gao Eilis Hannon Hona Lee Harrington Renate Houts Meeraj Kothari Dayoon Kwon Jonathan Mill Joel Schwartz Pantel Vokonas Cuicui Wang Benjamin S Williams Terrie E Moffitt |
| author_sort | Daniel W Belsky |
| collection | DOAJ |
| description | Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).
Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.
Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.
Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.
Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1. |
| first_indexed | 2024-04-11T10:47:10Z |
| format | Article |
| id | doaj.art-ed8e667fe7084ba990e0b7e3f557bdcc |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:47:10Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ed8e667fe7084ba990e0b7e3f557bdcc2022-12-22T04:29:02ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.73420DunedinPACE, a DNA methylation biomarker of the pace of agingDaniel W Belsky0https://orcid.org/0000-0001-5463-2212Avshalom Caspi1David L Corcoran2Karen Sugden3Richie Poulton4Louise Arseneault5Andrea Baccarelli6Kartik Chamarti7Xu Gao8Eilis Hannon9https://orcid.org/0000-0001-6840-072XHona Lee Harrington10Renate Houts11Meeraj Kothari12Dayoon Kwon13Jonathan Mill14https://orcid.org/0000-0003-1115-3224Joel Schwartz15Pantel Vokonas16Cuicui Wang17Benjamin S Williams18Terrie E Moffitt19Department of Epidemiology & Butler Columbia Aging Center, Columbia University, New York, United StatesCenter for Genomic and Computational Biology, Duke University, Durham, United StatesCenter for Genomic and Computational Biology, Duke University, Durham, United StatesDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesDepartment of Psychology, University of Otago, Otago, New ZealandSocial, Genetic, and Developmental Psychiatry Centre, King's College London, London, United KingdomDepartment of Environmental Health Sciences, Columbia University, New York, United StatesDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesDepartment of Occupational and Environmental Health, Peking University, Beijing, ChinaComplex Disease Epigenetics Group, University of Exeter, Exeter, United KingdomDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesRobert N Butler Columbia Aging Center, Columbia University, Brooklyn, United StatesRobert N Butler Columbia Aging Center, Columbia University, New York, United StatesComplex Disease Epigenetics Group, University of Exeter, Exeter, United KingdomDepartment of Environmental Health Sciences, Harvard TH Chan School of Public Health, Harvard University, Boston, United StatesDepartment of Medicine, VA Boston Healthcare System, Boston, United StatesDepartment of Environmental Health Sciences, Harvard TH Chan School of Public Health, Harvard University, Boston, United StatesDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesDepartment of Psychology and Neuroscience, Duke University, Durham, United StatesBackground: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome). Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets. Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.https://elifesciences.org/articles/73420aginggerosciencebiological aginggerontologyDNA methylationepigenetic |
| spellingShingle | Daniel W Belsky Avshalom Caspi David L Corcoran Karen Sugden Richie Poulton Louise Arseneault Andrea Baccarelli Kartik Chamarti Xu Gao Eilis Hannon Hona Lee Harrington Renate Houts Meeraj Kothari Dayoon Kwon Jonathan Mill Joel Schwartz Pantel Vokonas Cuicui Wang Benjamin S Williams Terrie E Moffitt DunedinPACE, a DNA methylation biomarker of the pace of aging eLife aging geroscience biological aging gerontology DNA methylation epigenetic |
| title | DunedinPACE, a DNA methylation biomarker of the pace of aging |
| title_full | DunedinPACE, a DNA methylation biomarker of the pace of aging |
| title_fullStr | DunedinPACE, a DNA methylation biomarker of the pace of aging |
| title_full_unstemmed | DunedinPACE, a DNA methylation biomarker of the pace of aging |
| title_short | DunedinPACE, a DNA methylation biomarker of the pace of aging |
| title_sort | dunedinpace a dna methylation biomarker of the pace of aging |
| topic | aging geroscience biological aging gerontology DNA methylation epigenetic |
| url | https://elifesciences.org/articles/73420 |
| work_keys_str_mv | AT danielwbelsky dunedinpaceadnamethylationbiomarkerofthepaceofaging AT avshalomcaspi dunedinpaceadnamethylationbiomarkerofthepaceofaging AT davidlcorcoran dunedinpaceadnamethylationbiomarkerofthepaceofaging AT karensugden dunedinpaceadnamethylationbiomarkerofthepaceofaging AT richiepoulton dunedinpaceadnamethylationbiomarkerofthepaceofaging AT louisearseneault dunedinpaceadnamethylationbiomarkerofthepaceofaging AT andreabaccarelli dunedinpaceadnamethylationbiomarkerofthepaceofaging AT kartikchamarti dunedinpaceadnamethylationbiomarkerofthepaceofaging AT xugao dunedinpaceadnamethylationbiomarkerofthepaceofaging AT eilishannon dunedinpaceadnamethylationbiomarkerofthepaceofaging AT honaleeharrington dunedinpaceadnamethylationbiomarkerofthepaceofaging AT renatehouts dunedinpaceadnamethylationbiomarkerofthepaceofaging AT meerajkothari dunedinpaceadnamethylationbiomarkerofthepaceofaging AT dayoonkwon dunedinpaceadnamethylationbiomarkerofthepaceofaging AT jonathanmill dunedinpaceadnamethylationbiomarkerofthepaceofaging AT joelschwartz dunedinpaceadnamethylationbiomarkerofthepaceofaging AT pantelvokonas dunedinpaceadnamethylationbiomarkerofthepaceofaging AT cuicuiwang dunedinpaceadnamethylationbiomarkerofthepaceofaging AT benjaminswilliams dunedinpaceadnamethylationbiomarkerofthepaceofaging AT terrieemoffitt dunedinpaceadnamethylationbiomarkerofthepaceofaging |