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A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup

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Recent advances indicate that biological aging is a potentially modifiable driver of late-life function and chronic disease and have led to the development of geroscience-guided therapeutic trials such as TAME (Targeting Aging with MEtformin). TAME is a proposed randomized clinical trial using metformin to affect molecular aging pathways to slow the incidence of age-related multi-morbidity and functional decline. In trials focusing on clinical end-points (e.g., disease diagnosis or death), biomarkers help show that the intervention is affecting the underlying aging biology before sufficient clinical events have accumulated to test the study hypothesis. Since there is no standard set of biomarkers of aging for clinical trials, an expert panel was convened and comprehensive literature reviews conducted to identify 258 initial candidate biomarkers of aging and age-related disease. Next selection criteria were derived and applied to refine this set emphasizing: (1) measurement reliability and feasibility; (2) relevance to aging; (3) robust and consistent ability to predict all-cause mortality, clinical and functional outcomes; and (4) responsiveness to intervention. Application of these selection criteria to the current literature resulted in a short list of blood-based biomarkers proposed for TAME: IL-6, TNFα-receptor I or II, CRP, GDF15, insulin, IGF1, cystatin C, NT-proBNP, and hemoglobin A1c. The present report provides a conceptual framework for the selection of blood-based biomarkers for use in geroscience-guided clinical trials. This work also revealed the scarcity of well-vetted biomarkers for human studies that reflect underlying biologic aging hallmarks, and the need to leverage proposed trials for future biomarker discovery and validation.

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This study received financial support from the American Federation for Aging Research (AFAR); the Glenn Center for the Biology of Human Aging (Paul Glenn Foundation for Medical Research); National Institutes of Health: K01 AG059837-01 (JNJ), P30 AG021332 (SKB, JNJ); R01 AG048023, R01 AG052608, R35 GM124922 (GAK); P30 AG038072 (NB); R01 AG023629 (ABN), and supported in part by the Intramural Research Program of the National Institute on Aging, National Institute of Health.

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Correspondence to Jamie N. Justice.

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JNJ, NB, JB, JD, MAE, LF, SBK, SM, ABN, MP, and GAK report no conflicts of interest to this work. VRA was the MedStar Health Research Institute’s principal clinical trial investigator for studies involving Elcelyx (delayed release metformin).

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Justice, J.N., Ferrucci, L., Newman, A.B. et al. A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup. GeroScience 40, 419–436 (2018).

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