#5-23E. Decoding the Aging Clock: How Epigenetic and Inflammatory Accelerations Drive Intrinsic Capacity Decline (JAMA Netw Open, 2026)

How can we intercept functional decline before it physically manifests in our aging patients? This prospective cohort study of 970 adults investigated the associations of accelerated epigenetic and inflammatory aging with global intrinsic capacity (IC), a composite of physical and mental domains. Over a 3-year follow-up, accelerated epigenetic aging, particularly measured via GrimAge, was consistently associated with lower global IC, showing more pronounced detrimental effects with advancing age and in males. Crucially, the most innovative finding is that the co-occurrence of both accelerated epigenetic and inflammatory aging—representing multidimensional biological aging—leads to significantly steeper, synergistic functional decline. However, when critically appraising these results, clinicians must note that biological aging was assessed at a single baseline timepoint over a relatively short 3-year follow-up, limiting insights into long-term biomarker dynamics and causal relationships. Nevertheless, these insights suggest that biological aging clocks could revolutionize preventive medicine, helping physicians identify high-risk individuals at a subclinical stage to guide timely, personalized longevity interventions.

Citation: Laure Rouch, Philipe De Souto Barreto, Yves Rolland, Sophie Guyonnet, Philippe Cestac, Wan-Hsuan Lu, Jean-Marc Lemaitre, Paul Bensadoun, David Furman, Bruno Vellas, Sandrine Andrieu. Accelerated Epigenetic and Inflammatory Aging and Intrinsic Capacity. JAMA Network Open. 2026.

DOI: 10.1001/jamanetworkopen.2026.24102

URL: https://doi.org/10.1001/jamanetworkopen.2026.24102

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