By measuring population ageing rates, DunedinPACE can predict future disease and mortality and improve our understanding of factors that drive accelerated ageing in at-risk populations.
As the proportion of people above the age of 65 is rapidly growing, frailty has become a major obstacle for individuals within this age group as it is strongly linked to disability and hospitalisation. As an intervention, researchers have been exploring various therapeutic agents and strategies that can improve the healthspan of the elderly population. However, to develop effective therapeutics, it is crucial to precisely understand the underlying mechanisms of ageing. In recent years, scientists have found a link between DNA methylation alterations and ageing and age-related diseases. Currently, it has been recognised that DNA methylation biomarkers can determine the biological age of any tissue across the entire human lifespan, even during development, urging the development of effective DNA methylation tests.
Now, scientists at the Columbia University Mailman School of Public Health have created a novel blood test that measures the pace of biological ageing by analysing DNA methylation marks in white blood cells. Their new test, called DunedinPACE, is named after the Dunedin Birth Cohort that was used to develop it and PACE stands for Pace of Aging Computed from the Epigenome.
“What makes DunedinPACE unique is that, whereas other tests aim to measure how old or young a person is, DunedinPACE measures whether you are ageing quickly or slowly,” said Daniel Belsky, Ph.D., assistant professor of epidemiology at Columbia Mailman School and a researcher at the Columbia Aging Center. In doing so, DunedinPACE provides greater sensitivity in identifying the effects of interventions that aim to delay ageing or of exposures that accelerate ageing.
“Whereas other measures of ageing are designed to capture all ageing-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.”
During development, the researchers tracked the changes in 19 biomarkers of organ-system integrity in 1,000 individuals making up the Dunedin Study birth cohort. The cohort was first enrolled in the study at birth in 1972-1973 and have been followed up ever since, most recently when the cohort turned 45 years old. For the purpose of modelling the Pace of Ageing, Belsky and colleagues used data collected from the participants when they were aged 26, 32, 38, and 45 years. By using a single-year birth cohort to develop the measure, the researchers eliminated possible biases that may arise in studies that compare older and younger individuals, such as survival bias and historical differences in exposure. Moreover, by examining the changes that occurred within the study members’ bodies as they aged between 26 and 45, the researchers ensured that DunedinPACE measures ageing-related changes occurring during adult life.
In their present study, the scientists discovered that midlife and older adults with faster DunedinPACE faced a higher risk for disability, incident chronic disease, and mortality. Furthermore, DunedinPACE was correlated with the measure of biological age that was derived from blood chemistry and DNA methylation data across the lifespan. DunedinPACE also correlated with the participants’ subjective perceptions of their own health. Interestingly, the team detected a faster Pace of Aging in young adults who had been exposed to poverty and victimisation.
“In sum, DunedinPACE represents a novel measure of ageing that can complement existing DNA methylation measures of ageing to help advance the frontiers of geroscience,” noted Belsky.
Having established the reliability and potential of DunedinPACE as a new, single-time-point measure that quantifies the Pace of Aging with whole blood samples, the researchers believe that it can be readily used in most DNA methylation datasets and to complement existing methylation measures of ageing.
“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 ageing in at-risk populations and identify interventions that can slow ageing to build ageing health equity,” said Belsky. [APBN]
Source: Belsky at al. (2022). DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife, 11, e73420.