Researchers develop a new biomarker designed to measure how quickly people are aging biologically, rather than simply how old they are

Researchers have developed a new biological aging clock based on data from the Framingham Heart Study Offspring Cohort, offering a potentially more informative way to measure the pace at which biological aging is occurring.

The new biomarker builds on the concept of “Pace of Aging,” an approach designed to capture the rate of age-related deterioration rather than relying solely on chronological age. The researchers say this distinction could be important for evaluating interventions intended to slow or reverse aspects of aging.

In recent years, scientists have developed numerous “aging clocks” using machine learning to identify biological changes associated with increasing age. These clocks can draw on information ranging from DNA methylation to other molecular and physiological measurements. However, because many are trained primarily to predict chronological age or survival, their biological meaning and usefulness for evaluating anti-aging interventions can be difficult to determine.

Chronological age also presents a fundamental challenge. Older people who remain available for study have, by definition, survived longer than many of their peers. As a result, biological differences between younger and older participants may reflect not only the accumulation of age-related damage but also differences in resilience and survival.

The Pace of Aging approach attempts to address this problem by focusing instead on how rapidly biological function is changing.

The original Pace of Aging measure was developed using approximately 20 years of follow-up data from participants in the Dunedin Longitudinal Study. Researchers combined changes in multiple measures of organ function to estimate the rate at which an individual’s physiological systems were deteriorating.

Importantly, that measure responded to calorie restriction in the CALERIE clinical trial. Calorie restriction is one of the most consistently studied interventions for slowing aspects of aging in laboratory animals, making the finding particularly relevant to efforts to develop biomarkers that can be used in human trials.

However, researchers faced an important question: Was the result caused by the biomarker’s ability to measure the rate of aging, or simply because the people used to develop the biomarker were demographically similar to those enrolled in the CALERIE trial?

To investigate, the team developed a new Pace of Aging biomarker using the Framingham Heart Study Offspring Cohort, an older-adult population that had previously been used to develop the GrimAge epigenetic clock.

The researchers adapted their Pace of Aging methodology to accommodate a cohort in which participants differed in age and had varying amounts of follow-up data for measures of organ function. They then used these data to create a new DNA methylation-based biomarker of the Pace of Aging.

The results provided several encouraging findings.

When tested in independent cohorts, the new biomarker demonstrated exceptional technical reliability. It also showed a pattern of increasingly rapid biological aging with advancing chronological age, replicating an observation previously made with the original Pace of Aging biomarkers developed from the Dunedin Study.

Most importantly, the new biomarker also responded to intervention. When researchers analyzed data from the CALERIE randomized controlled trial of calorie restriction in healthy, non-obese adults, the Framingham-derived Pace of Aging measure indicated that calorie restriction slowed the rate of biological aging.

The finding is significant because it suggests that the response observed with the original Pace of Aging biomarker was not simply a consequence of demographic similarities between the biomarker-development population and clinical-trial participants.

Instead, the results strengthen the case for developing aging biomarkers around biological processes that interventions are actually intended to change.

Rather than asking only, “How old does this person look biologically?” a Pace of Aging biomarker asks a potentially more useful question: “How quickly is this person’s biology changing?”

That distinction could ultimately make aging biomarkers more valuable in clinical research. If a measure can detect changes in the rate of biological deterioration over a relatively short period, researchers may be able to evaluate potential longevity interventions without waiting decades for differences in disease incidence or lifespan to emerge.

The researchers caution that aging is a complex, multifaceted process and that no single biomarker is likely to capture every aspect of it. Nevertheless, the new Framingham-derived Pace of Aging clock provides another tool for investigating whether interventions can alter the trajectory of human biological aging.

The study therefore adds to a growing effort to move aging research beyond simply measuring how old we are toward measuring how rapidly we are aging, a shift that could prove increasingly important as researchers search for interventions capable of extending healthy human lifespan.