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DunedinPACE reveals a wide range of population aging rates and can predict future disease and mortality

Researchers at Columbia University Mailman School of Public Health have developed a new blood test to measure the rate 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 (acronym for Pace of Aging Computed from the Epigenome) is a new addition to a rapidly growing list of DNA methylation tests designed to measure aging and provides added value beyond the current state of technical. The results are published online in the journal e-Life.

“What makes DunedinPACE unique is that while other tests aim to measure how old or young a person is, DunedinPACE measures whether you are aging rapidly or slowly,” said Daniel Belsky, PhD, Professor assistant epidemiologist at the Columbia Mailman School and researcher. at the Columbia Aging Center. This design could make DunedinPACE a more sensitive tool for detecting the effects of interventions aimed at slowing aging or exposures that accelerate aging processes. “While other measures of aging are designed to capture all age-related changes accumulated over the lifetime, our measure focuses on changes that have occurred in the recent past,” Belsky explained. “What is striking is that, even with this narrower focus, DunedinPACE is every bit as accurate as the best of the tests currently available at predicting disease, disability and mortality in the future, and it adds value to risk assessments beyond 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 birth cohort of 1,000 Dunedin Study members, who were first enrolled in the study at birth in 1972-1973 and have been followed since, most recently around their 45th birthday. This study used data collected from participants when they were all 26, 32, 38 and 45 years old.

The use of a single-year birth cohort to develop the measure ensures that DunedinPACE is not contaminated with biases that may affect studies comparing older people to younger people, including biases of survival and historical exposure differences. Analyzing the changes that occurred within the study members’ bodies as they aged during the 20-year follow-up also ensures that DunedinPACE measures age-related changes that occur 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 Longitudinal Twin Environmental Risk Study (E -Risk).

In the current analysis, middle-aged and older adults with faster DunedinPACE had an increased risk of incident chronic disease, disability, and mortality; Across the lifespan, DunedinPACE has been correlated with measures of biological age derived from blood chemistry and DNA methylation data, and with participants’ subjective perceptions of seeking their own health. It also indicated a faster rate of aging among young adults with a history of exposure to poverty and victimization.

“In sum, DunedinPACE represents a new measure of aging that can complement existing DNA methylation measures of aging to help advance the frontiers of geroscience,” noted Belsky, who also works at Robert N. Butler Columbia. Aging Center, Columbia Mailman School.

The current analysis establishes DunedinPACE as a new point-in-time metric that quantifies the rate of aging with whole blood samples that can be easily implemented in most DNA methylation datasets, making it immediately available for testing in a wide range of existing datasets as a supplement to existing methylation measurements of aging.

“There is growing interest in technologies that can measure biological age, defined as the degree of biological aging of a person relative to their date of birth. Our study reveals that it is also possible to measure the rate of aging, or the rate at which a person’s body is declining.Together, these measures can help us understand the factors that lead to accelerated aging in at-risk populations and identify interventions that can slow aging to strengthen equity in aging health.

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, New Zealand; 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, TH Chan Harvard School of Public Health; and P Vokonas, Veterans Affairs Boston Healthcare System, Boston University School of Medicine

The research was supported by the National Institute on Aging (Grants AG032282, AG061378, AG066887); Medical Research Council (Grant P005918).