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Review
. 2024 Feb;30(2):360-372.
doi: 10.1038/s41591-023-02784-9. Epub 2024 Feb 14.

Validation of biomarkers of aging

Affiliations
Review

Validation of biomarkers of aging

Mahdi Moqri et al. Nat Med. 2024 Feb.

Abstract

The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.

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Conflict of interest statement

Conflict of Interest statement: M.M., V.S., M.P.S, and V.N.G. have filed a patent on measuring cellular aging. C.H. is also affiliated with the Institute for Biomedical Aging Research, Universitat Innsbruck, Austria and an honorary research fellow at the Department of Women’s Cancer, EGA Institute for Women’s Health, University College London, United Kingdom. C.H. is a shareholder of Sola Diagnostics GmbH, and named as inventor on a patent on an epigenetic clock indicative of breast cancer risk. J.N.J. is also affiliated with the Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA and the XPRIZE Foundation, Culver City, CA, USA. J.N.J. serves on the advisory board for the American Federation for Aging Research (AFAR)’s Finding Aging biomarkers by Searching existing Trials (FAST) Initiative and the editorial board of Journals of Gerontology Series A Biological Sciences, eLife, and Experimental Gerontology. D.B. is also affiliated with the Child Brain Development Network, Canadian Institute for Advanced Research and SocioMed Research Nucleus, Universidad Mayor, Santiago, Chile. D.B. is an inventor of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic. A.H.-C. has built epigenetic aging metrics that are licensed by Elysium Health through Yale University. B.H.C. owns stock in Illumina Inc., the manufacturer of the DNA methylation arrays used in epigenetic biomarkers of aging, and is listed as a co-inventor in filed patents on commercial applications of epigenetic prediction models. A.A.C. is a founder, president, and majority shareholder at Oken Health. R.E.M has received a speaker fee from Illumina and is an advisor to the Epigenetic Clock Development Foundation and Optima Partners. M.W. is also affiliated with the Institute for Biomedical Aging Research, Universität Innsbruck, Austria. M.W. is a shareholder of Sola Diagnostics GmbH, and named as inventor on a patent on an epigenetic clock indicative of breast cancer risk. K.F. is CEO of BioAge Labs P.O.F. is an employee and stakeholder in Gero PTE. A.Z. is the founder and CEO of Insilico Medicine, a clinical-stage generative AI and robotics biotechnology company specializing in aging research N.B. is the Scientific Director of the American Federation for Aging Research (AFAR), on the board of the executive committee of the Longevity Biotech Association, and advisor on the Board of the Academy for Health and Lifespan Research. D.P.K has received a grant from Solarea Bio and royalties from Wolters Kluwer. D.P.K sits on the Scientific Advisory Boards of Solarea Bio, Pfizer and Reneo and has participated on the Data Safety Monitoring Board for the AgNovos Healthcare osteoporosis treatment trial. E.V. is a scientific co-founder of Napa Therapeutics and BHB Therapeutics, serves on the scientific advisory board of Seneque, and is named co-inventor on a patent relating to an epigenetic clock robust to cell composition changes. A.B.M. declares to be Chief Medical Officer of NU. V.S is Cofounder, SAB Chair and Head of research of Turn Biotechnologies. M.P.S. is a cofounder and scientific advisor of Personalis, SensOmics, Qbio, January AI, Fodsel, Filtricine, Protos, RTHM, Iollo, Marble Therapeutics, Crosshair Therapeutics and Mirvie. He is a scientific advisor of Jupiter, Neuvivo, Swaza, Mitrix. S.H. is a founder of the nonprofit Epigenetic Clock Development Foundation that licenses patents surrounding epigenetic clocks. The Regents of the University of California is the sole owner of a patent application directed at GrimAge and other epigenetic clocks for which S.H. is a named inventor.

Figures

Figure 1.
Figure 1.. Different approaches to cohort study design in the context of biomarkers of aging.
Biomarkers of aging are commonly validated using cross-sectional or longitudinal study designs. Cross-sectional studies involve measurement of biomarkers and chronological age or aging-related outcome data at a single time point. These data can only support association of these measures at that time point. Longitudinal designs, on the other hand, allow for assessment of predictive validity of biomarkers measured at one time point and future aging-related outcomes.
Figure 2.
Figure 2.. Validation of biomarkers of aging with different numbers of cohorts or biomarkers.
a) Most existing biomarkers have been developed using data from a single cohort and some have been validated in a second external cohort. Analysis of multiple biomarkers across multiple cohorts allows for a meta-analysis comparison across multiple cohorts. b) Biomarker validation studies need to consider different sources of variation, such as heterogeneity in population characteristics, sample collections, data preprocessing, analyses, and reporting.

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References

    1. Moqri M. et al. Biomarkers of aging for the identification and evaluation of longevity interventions. Cell 186, 3758–3775 (2023). - PMC - PubMed
    1. Moqri M. et al. PRC2 clock: a universal epigenetic biomarker of aging and rejuvenation. 2022.06.03.494609 Preprint at 10.1101/2022.06.03.494609 (2022). - DOI
    1. Poganik JR et al. Biological age is increased by stress and restored upon recovery. Cell Metab. 35, 807–820.e5 (2023). - PMC - PubMed
    1. Lu AT et al. DNA methylation GrimAge version 2. Aging 14, 9484–9549 (2022). - PMC - PubMed
    1. Tanaka T. et al. Plasma proteomic biomarker signature of age predicts health and life span eLife 9, e61073 (2020). - PMC - PubMed

Extended Data References

    1. Li Q. et al. An objective metric of individual health and aging for population surveys. Popul. Health Metr 20, 11 (2022). - PMC - PubMed
    1. Marioni RE et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 16, 1–12 (2015). - PMC - PubMed
    1. Huan T. et al. Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits. Aging Cell 17, e12687 (2018). - PMC - PubMed
    1. Tian YE et al. Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nat. Med 29, 1221–1231 (2023). - PubMed
    1. Kristie J. et al. Glycans Are a Novel Biomarker of Chronological and Biological Ages. J. Gerontol. A. Biol. Sci. Med. Sci 69, 779–789 (2014). - PMC - PubMed