Article Synopsis
- Age-related decline in intrinsic capacity (IC) reflects the combination of physical and mental abilities and emphasizes maintaining function for healthy aging rather than just treating diseases.
- Researchers developed an IC clock, a predictor based on DNA methylation, using data from a diverse cohort of 1,014 individuals aged 20-102 years, assessing various health and well-being factors.
- The IC clock not only outperforms existing epigenetic clocks in predicting all-cause mortality but also shows strong correlations with immune and inflammatory biomarkers, clinical health outcomes, and lifestyle factors, making it a validated tool for understanding aging.
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Article Abstract
Age-related decline in intrinsic capacity (IC), defined as the sum of an individual's physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20-102 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270914 | PMC |
| http://dx.doi.org/10.1038/s43587-025-00883-5 | DOI Listing |
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