Epigenetic Clock Measures Functional Aging Through Intrinsic Capacity

A team led by researchers from the Buck Institute for Research on Aging has introduced the IC Clock, a biological age “clock” designed to estimate how well a person is aging by measuring intrinsic capacity (IC), rather than simply tracking chronological age. As described in Nature Aging, the IC Clock evaluates six key functions—mobility, cognition, mental health, vision, hearing, and nutrition/vitality—that together define healthy aging.

Senior author David Furman explained, “Maintaining function during the aging process is what matters to older adults. Function should inform medical care instead of focusing on getting patients to some disease-free state.” The concept of intrinsic capacity was developed by the World Health Organization, which recognized its decline as a condition in 2022.

Developed through collaboration among scientists at the Buck Institute, IHU HealthAge, INSERM, and Universite de Montpellier, the IC Clock’s creation was based on data from the INSPIRE-T cohort—a group of 1,000 individuals aged 20 to 102 in Toulouse, France, followed for up to 4 years. This cohort provided both functional and lifestyle data, as well as annual biospecimens such as blood, urine, saliva, and dental plaque.

The IC Clock uses DNA methylation signals from blood or saliva to assess IC non-invasively. After being trained on INSPIRE-T data, it was validated with the Framingham Heart Study. According to Furman, the IC Clock “outperformed all first- and second-generation aging clocks in predicting overall mortality.” Higher IC Clock scores were associated with better immune function, lower inflammation, and healthier lifestyle choices.

Efforts are underway to develop a dried-blood spot version of the IC Clock, making it more accessible for widespread use. Furman noted, “If we can offer a scalable, affordable molecular level tool to assess functional decline, the IC Clock could help clinicians, researchers, and policy makers better identify at-risk individuals and tailor interventions that promote a longer healthier life.”

The IC Clock will also be used in the XPRIZE Healthspan competition, where it will help track responses to interventions aimed at improving intrinsic capacity in older adults.