Summary: A newly developed blood test can measure the pace of biological aging by identifying specific DNA methylation marks.
Source: Columbia University
Researchers at Columbia University Mailman School of Public Health have developed a new blood test to measure the pace of biological aging.
Based on an analysis of chemical tags on the DNA contained in white blood cells, called DNA methylation marks, the new test is named DunedinPACE, after the Dunedin Birth Cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome) is a new addition to a fast-growing list of DNA methylation tests designed to measure aging and contributes value-added over and above the current state of the art.
The findings are published online in the journal e-Life.
“What makes DunedinPACE unique is that, whereas other tests aim to measure how old or young a person is, DunedinPACE measures whether you are aging quickly or slowly,” said Daniel Belsky, PhD, assistant professor of epidemiology at Columbia Mailman School and a researcher at the Columbia Aging Center.
This design could make DunedinPACE more a more sensitive tool to detect effects of interventions that aim to slow aging or of exposures that accelerate aging processes.
“Whereas other measures of aging are designed to capture all aging-related change accumulated across the life course, our measure is focused on changes occurring over the recent past,” explained Belsky.
“What is striking is that, even with this more restricted focus, DunedinPACE is equally precise as the best of the currently available tests in predicting disease, disability, and mortality in the future, and it adds value to risk assessments over and above these measures.”
Developed by Belsky and colleagues at Duke University and the University of Otago, DunedinPACE tracks changes in 19 biomarkers of organ-system integrity in the 1000-member Dunedin Study birth cohort, who were first enrolled in the study at birth in 1972-1973 and have been followed up ever since, most recently at the time of their 45th birthday. This study used data collected from the participants when they were all aged 26, 32, 38, and 45 years.
The use of a single-year birth cohort to develop the measure ensures DunedinPACE is not contaminated by biases that may affect studies that compare older to younger people, including survival bias, historical differences in exposure. The analysis of changes that occurred within Study members’ bodies as they aged over the 20-year follow-up also ensures that DunedinPACE measures aging-related changes occurring during adult life.
In addition to the Dunedin Study, the researchers also used data from the Understanding Society Study, the Normative Aging Study, the Framingham Heart Study, and the Environmental Risk (E- Risk) Longitudinal Twin Study.
In the current analysis, midlife and older adults with faster DunedinPACE were at increased risk for incident chronic disease, disability, and mortality; across the lifespan, DunedinPACE was correlated with measures of biological age derived from blood chemistry and DNA methylation data, and with research participants’ subjective perceptions of their own health. It also indicated faster Pace of Aging in young adults with histories of exposure to poverty and victimization.
“In sum, DunedinPACE represents a novel measure of aging that can complement existing DNA methylation measures of aging to help advance the frontiers of geroscience,” noted Belsky, who is also with the Robert N. Butler Columbia Aging Center, Columbia Mailman School.
The current analysis establishes DunedinPACE as a novel single-time-point measure that quantifies Pace of Aging with whole blood samples, that can be readily implemented in most DNA methylation datasets, making it immediately available for testing in a wide range of existing datasets as a complement to existing methylation measures of aging.
“There is growing interest in technologies to measure a biological age, defined as how much older or younger a person is biologically than their birthdate would predict. Our study reveals that it is also possible to measure Pace of Aging, or how fast a person’s body is declining. Together, these measurements can help us understand the factors that drive accelerated aging in at-risk populations and identify interventions that can slow aging to build aging health equity.”
Co-authors are A Caspi, TE Moffitt, King’s College, UK and Duke University; K Sugden, K Chamarti, HL Harrington, R Houts, B Williams, Duke University; R Poulton, University of Otago, NZ; L Arseneault, King’s College, UK; A. Baccarelli, Columbia University Mailman School of Public Health; X Gao, Peking University; E Hannon, J Mill, University of Exeter, UK; M Kothari, D Kwon, Robert N. Butler Columbia Aging Center, Columbia Mailman School of Public Health; J Schwartz, C Wang, Harvard TH Chan School of Public Health; and P Vokonas, Veterans Affairs Boston Healthcare System, Boston University School of Medicine
Funding: The research was supported by National Institute on Aging (grants AG032282,AG061378,AG066887); Medical Research Council (grant P005918).
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. 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 1972-3 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.