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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- FC · DOI · Paper page
- Authors
- Justice, J. N., Ferrucci, L., Newman, A. B., Aroda, V. R., Bahnson, J. L., Divers, J., Espeland, M. A., Marcovina, S., Pollak, M. N., Kritchevsky, S. B., Barzilai, N., & Kuchel, G. A.
- Affiliations
- Wake Forest University Health Sciences (US)
- National Institutes of Health (US)
- University of Pittsburgh (US)
- Brigham and Women's Hospital (US)
- University of Washington (US)
- Albert Einstein College of Medicine (US)
- University of Connecticut (US)
- Corresponding author
- Justice, Jamie N.
- ORCID
- Venue
- GeroScience
- Published
- 2018-08-27
- Volume
- 40
- Issue
- 5-6
- Pages
- 419-436
- ISSN
- 2152-4041 (ISSN-L)
- 2509-2715
- 2509-2723
- PMC
- PMC6294728
- OpenAlex
- W2889170508
- Cited by
- 359
- References
- 170
- Citations by year
- 2026: 60 · 2025: 34 · 2024: 43 · 2023: 55 · 2022: 54 · 2021: 39 · 2020: 41 · 2019: 29 · 2018: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- GeroScience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Federation for Aging Research
- Paul Glenn Foundation for Medical Research (NA)
- National Institute on Aging (K01 AG059837-01, P30 AG021332, AG048023, AG052608, P30 AG038072, R01 AG023629, P30 AG024827, Intramural Research Program)
- National Institute of General Medical Sciences (GM124922)
- Division of Loan Repayment (L30 AG057113-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Keywords
- blood-based biomarkers, biomarker selection, metformin, biological aging, age-related diseases, hallmarks of aging, interleukin-6, TNF-alpha receptor, C-reactive protein, GDF15, insulin, insulin-like growth factor I, cystatin C, NT-proBNP, HbA1c, all-cause mortality prediction, functional decline, biomarker validation
- MeSH terms
- Aging, Humans, Hypoglycemic Agents, Metformin, Reproducibility of Results, Biomarkers, Randomized Controlled Trials as Topic, Biomedical Research
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