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

Jamie N. Justice, Luigi Ferrucci, Anne B. Newman, Vanita R. Aroda, Judy L. Bahnson, Jasmin Divers, Mark A. Espeland, Santica Marcovina, Michael N. Pollak, Stephen B. Kritchevsky, Nir Barzilai, George A. Kuchel

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalGeroScience
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Metformin
Biomarkers
Clinical Trials
Patient Selection
Interleukin-6 Receptors
Cystatin C
Tumor Necrosis Factor Receptors
Hemoglobins
Chronic Disease
Randomized Controlled Trials
Insulin
Morbidity
Mortality
Incidence

Keywords

  • Aging
  • Biomarkers
  • Epidemiology
  • Inflammation
  • Metformin
  • Mortality
  • Randomized controlled trial

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Justice, J. N., Ferrucci, L., Newman, A. B., Aroda, V. R., Bahnson, J. L., Divers, J., ... Kuchel, G. A. (Accepted/In press). A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup. GeroScience. https://doi.org/10.1007/s11357-018-0042-y

A framework for selection of blood-based biomarkers for geroscience-guided clinical trials : report from the TAME Biomarkers Workgroup. / Justice, Jamie N.; Ferrucci, Luigi; Newman, Anne B.; Aroda, Vanita R.; Bahnson, Judy L.; Divers, Jasmin; Espeland, Mark A.; Marcovina, Santica; Pollak, Michael N.; Kritchevsky, Stephen B.; Barzilai, Nir; Kuchel, George A.

In: GeroScience, 01.01.2018.

Research output: Contribution to journalArticle

Justice, JN, Ferrucci, L, Newman, AB, Aroda, VR, Bahnson, JL, Divers, J, Espeland, MA, Marcovina, S, Pollak, MN, Kritchevsky, SB, Barzilai, N & Kuchel, GA 2018, 'A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup', GeroScience. https://doi.org/10.1007/s11357-018-0042-y
Justice, Jamie N. ; Ferrucci, Luigi ; Newman, Anne B. ; Aroda, Vanita R. ; Bahnson, Judy L. ; Divers, Jasmin ; Espeland, Mark A. ; Marcovina, Santica ; Pollak, Michael N. ; Kritchevsky, Stephen B. ; Barzilai, Nir ; Kuchel, George A. / A framework for selection of blood-based biomarkers for geroscience-guided clinical trials : report from the TAME Biomarkers Workgroup. In: GeroScience. 2018.
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abstract = "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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