Researchers continue to produce a fair number of new aging clocks every year to attempt to measure biological age. One might at this point ask whether the life science community should instead focus on better understanding and utilizing the best of the existing clocks. No new clock can be applied naively to the assessment of potential therapies to slow or reverse aging, as a new clock arrives with no understanding of how exactly the measures making it up relate to specific forms of damage and dysfunction that drive aging. One cannot predict whether the clock will accurately reflect changes in biological age or risk of age-related disease if, for example, senescent cells are cleared, or mitochondrial function improved. Nonetheless, it seems that more effort goes to making new clocks than is put towards the calibration of existing clocks.
In 2015, the World Health Organization (WHO) introduced the concept of intrinsic capacity (IC), defined as the sum of all physical and mental capacities that an individual can draw on at any point in their life. The International Classification of Diseases, 11th Revision, recently added 'aging-associated decline in IC' under code MG2A10, standardizing the clinical use of IC globally as a metric of functional aging. Since the inception of IC, many studies have developed IC scores and demonstrated its association with health-related factors.
Despite the advantages of using IC to assess functional ability, current methods to quantify it require equipment and trained personnel, and the molecular and cellular mechanisms underlying its age-associated decline are still poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20 to 102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities, and vitality. In the Framingham Heart Study, DNA methylation IC outperforms first-generation and second-generation epigenetic clocks in predicting all-cause mortality, and it is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors, and lifestyle choices. These findings establish the IC clock as a validated tool bridging molecular readouts of aging and clinical assessments of IC.
Link: https://doi.org/10.1038/s43587-025-00883-5
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