Immune aging biomarkers for clinical trials.

Andrea Cipriano, Jamie Justice, Jesse R Poganik, Mahdi Moqri, Omar O Abudayyeh, Jonathan Gootenberg, Laura Haynes, Yotam Levin, Daniel E Martin-Herranz, Arne N Akbar, Joan Mannick, Graham Pawelec, Shai S Shen-Orr, John Tsang, Wolfgang Wagner, Miriam Merad, Sacha Gnjatic, Alfred Gellhorn, Michael J Corley, George A Kuchel, Luigi Ferrucci, David Furman, Chiara M S Herzog

Department of Obstetrics & Gynecology, Stanford School of Medicine, Stanford University, Stanford, CA, USA. [email protected]. · pubmed

Paper

Abstract

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a translational framework to identify immune aging biomarkers for this purpose. We define five evaluation criteria for immune aging biomarkers and apply these to candidate biomarkers, discussing their utility in the context of a major international healthspan competition, XPRIZE Healthspan. Metrics encapsulating multidimensional aspects of immune function, inflammaging scores and functional assays performed best against our selection criteria. Finally, we identify promising emerging measures, together with critical gaps that must be addressed to develop reliable, predictive biomarkers of human immune competence. Our framework provides a coherent path toward actionable and clinically meaningful immune aging biomarkers capable of quantifying immune fitness and resilience, and accelerating the clinical translation of geroscience-guided interventions.

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Research summary

This paper establishes a translational framework and evaluation criteria for identifying immune aging biomarkers to quantify immune fitness and resilience in clinical trials. The work is relevant because it addresses the fundamental geroscience goal of developing reliable metrics to measure biological aging and immune competence, which are central to understanding and potentially intervening in the root causes of age-related decline.

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