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GeroScience

, Volume 40, Issue 5–6, pp 419–436 | Cite as

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

  • Jamie N. JusticeEmail author
  • 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
Review Article

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.

Keywords

Biomarkers Aging Metformin Randomized controlled trial Epidemiology Mortality Inflammation 

Notes

Funding disclosures

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.

Compliance with ethical standards

Conflicts of interest

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).

Supplementary material

11357_2018_42_MOESM1_ESM.docx (652 kb)
ESM 1 (DOCX 652 kb)

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Copyright information

© American Aging Association 2018

Authors and Affiliations

  • Jamie N. Justice
    • 1
    Email author
  • Luigi Ferrucci
    • 2
  • Anne B. Newman
    • 3
  • Vanita R. Aroda
    • 4
  • Judy L. Bahnson
    • 5
  • Jasmin Divers
    • 5
  • Mark A. Espeland
    • 5
  • Santica Marcovina
    • 6
  • Michael N. Pollak
    • 7
  • Stephen B. Kritchevsky
    • 1
  • Nir Barzilai
    • 8
  • George A. Kuchel
    • 9
  1. 1.Internal Medicine Section on Gerontology and Geriatrics, and the Sticht Center for Healthy Aging and Alzheimer’s PreventionWake Forest School of MedicineWinston-SalemUSA
  2. 2.National Institute on AgingNational Institutes of HealthBaltimoreUSA
  3. 3.Department of Epidemiology, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA
  4. 4.Department of Medicine, Division of Diabetes, Endocrinology, and Hypertension Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  5. 5.Department of Biostatistical SciencesWake Forest School of MedicineWinston-SalemUSA
  6. 6.Division of Metabolism, Endocrinology, and NutritionUniversity of WashingtonSeattleUSA
  7. 7.Department of Oncology, Jewish General HospitalMcGill UniversityMontrealCanada
  8. 8.Department of Medicine, Institute for Aging ResearchAlbert Einstein College of MedicineBronxUSA
  9. 9.UConn Center on AgingUniversity of Connecticut School of MedicineFarmingtonUSA

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