DunedinPACE, a DNA methylation biomarker of the pace of aging
dc.contributor.author | Belsky, DW | |
dc.contributor.author | Caspi, A | |
dc.contributor.author | Corcoran, DL | |
dc.contributor.author | Sugden, K | |
dc.contributor.author | Poulton, R | |
dc.contributor.author | Arseneault, L | |
dc.contributor.author | Baccarelli, A | |
dc.contributor.author | Chamarti, K | |
dc.contributor.author | Gao, X | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | Harrington, HL | |
dc.contributor.author | Houts, R | |
dc.contributor.author | Kothari, M | |
dc.contributor.author | Kwon, D | |
dc.contributor.author | Mill, J | |
dc.contributor.author | Schwartz, J | |
dc.contributor.author | Vokonas, P | |
dc.contributor.author | Wang, C | |
dc.contributor.author | Williams, BS | |
dc.contributor.author | Moffitt, TE | |
dc.date.accessioned | 2022-06-06T15:05:20Z | |
dc.date.issued | 2022-01-14 | |
dc.date.updated | 2022-06-06T14:23:05Z | |
dc.description.abstract | 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. | en_GB |
dc.description.sponsorship | US National Institute on Aging | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.format.extent | e73420- | |
dc.format.medium | Electronic | |
dc.identifier.citation | Vol. 11, article e73420 | en_GB |
dc.identifier.doi | https://doi.org/10.7554/eLife.73420 | |
dc.identifier.grantnumber | AG032282. | en_GB |
dc.identifier.grantnumber | AG061378 | en_GB |
dc.identifier.grantnumber | AG066887 | en_GB |
dc.identifier.grantnumber | MR/P005918/1 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/129848 | |
dc.identifier | ORCID: 0000-0001-6840-072X (Hannon, Eilis) | |
dc.identifier | ResearcherID: T-1349-2019 (Hannon, Eilis) | |
dc.identifier | ORCID: 0000-0003-1115-3224 (Mill, Jonathan) | |
dc.identifier | ScopusID: 55395957100 | 57211066410 (Mill, Jonathan) | |
dc.identifier | ResearcherID: B-3276-2010 (Mill, Jonathan) | |
dc.language.iso | en | en_GB |
dc.publisher | eLife Sciences Publications | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/35029144 | en_GB |
dc.relation.url | https://www.metadac.ac.uk/ukhls/ | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55763 | en_GB |
dc.rights | © 2022. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. | en_GB |
dc.title | DunedinPACE, a DNA methylation biomarker of the pace of aging | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2022-06-06T15:05:20Z | |
dc.identifier.issn | 2050-084X | |
exeter.article-number | ARTN e73420 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from eLife Sciences Publications via the DOI in this record | en_GB |
dc.description | Data availability: Datasets are available from the data owners. Data from the Dunedin and E-Risk Study can be accessed through agreement with the Study investigators. Instructions are available at https://sites.google.com/site/moffittcaspiprojects/. The data access application form can be downloaded here: https://sites.google.com/site/moffittcaspiprojects/forms-for-new-projects/concept-paper-template. Data from the Understanding Society Study is available through METADAC at https://www.metadac.ac.uk/ukhls/. All details are on the Metadac website (https://www.metadac.ac.uk/data-access-through-metadac/). The data access application form can be found here https://www.metadac.ac.uk/files/2019/02/v2.41-UKHLS-METADAC-application-form-2019-2hak8bv.docx. Data from the Normative Aging Study were obtained from the Study investigators. Data are accessible through dbGaP, accession phs000853.v1.p1. Data from the Framingham Heart Study were obtained from dbGaP, accession phs000007.v32.p13. GSE55763 is a publicly available dataset available from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55763). | en_GB |
dc.identifier.eissn | 2050-084X | |
dc.identifier.journal | eLife | en_GB |
dc.relation.ispartof | Elife, 11 | |
dc.rights.uri | https://creativecommons.org/publicdomain/zero/1.0/ | en_GB |
dcterms.dateAccepted | 2021-12-13 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-01-14 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2022-06-06T15:02:18Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2022-06-06T15:05:28Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-01-14 |
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Except where otherwise noted, this item's licence is described as © 2022. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.