Biomarkers are measurable characteristics that can be used to evaluate normal biological processes, diseases, or responses to treatment in patients. Using biomarkers to assess biological aging, or the increase in molecular and cellular damage over time, has recently gained popularity for its potential to predict longevity and quality of life. However, there are currently no guidelines for standardizing the development and validation of biomarkers of aging — a necessary process to ensure accurate and reliable outcomes in the clinic.
A new study led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, proposed a framework for future validation of aging biomarkers that could help translate them into clinically actionable tools.
To do this, the team examined population-based cohort studies of blood-based biomarkers of aging built using omic data. Using this information, they identified challenges in comparing the predictive strength of biomarkers, such as variations in study design and data collection methods, as well as inherent differences in population-specific traits.
The authors then provided recommendations to address these difficulties. They suggest that “multi-omic approaches” involving different technologies like metabolomics, proteomics and epigenetics, and transcriptomics will provide greater insights into biomarker predictive performance. Instead of relying only on mortality as an aging-related outcome, the researchers advocate for the consideration of biomarker associations with other health factors like functional decline, frailty, chronic disease and disability. In addition, they recommend standardizing omic data to enhance validation efforts. “Omics and biomarkers harmonization efforts, such as the Bio-learn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics.
The framework also encourages increased collaboration between research groups on large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations. Further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.
“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of aging,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. “We hope that our framework will help prioritize the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”
Read more in Nature Medicine.
Journal
Nature Medicine
Method of Research
Systematic review
Subject of Research
People
Article Title
Validation of biomarkers of aging
Article Publication Date
14-Feb-2024
COI 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, Universität Innsbruck, Austria and is an honorary research fellow at the Department of Women’s Cancer, EGA Institute for Women’s Health, University College London. C.H. is a shareholder of Sola Diagnostics and is named as an 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 and the XPRIZE Foundation. J.N.J. serves on the advisory board for the American Federation for Aging Research’s Finding Aging Biomarkers by Searching Existing Trials Initiative and the editorial board of the Journals of Gerontology Series A Biological Sciences, eLife and Experimental Gerontology. D.W.B. is also affiliated with the Child Brain Development Network, Canadian Institute for Advanced Research and SocioMed Research Nucleus and Universidad Mayor. D.W.B. is an inventor of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic. A.T.H.-C. is an inventor of epigenetic clocks that are the subject of a provisional patent and have been licensed to TruDiagnostic. A.T.H.-C. has also received consulting fees from TruDiagnostic and FOXO Biosciences. B.H.C. owns stock in Illumina, the manufacturer of the DNA methylation arrays used in epigenetic biomarkers of aging, and is listed as a co-inventor on 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. M.W. is a shareholder of Sola Diagnostics and is named as an inventor on a patent on an epigenetic clock indicative of breast cancer risk. K.F. is the CEO of BioAge Labs. P.O.F. is an employee and stakeholder of Gero. A.Z. is the founder and the 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, is on the board of the executive committee of the Longevity Biotech Association and is 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, Radius Health and Reneo and has participated in the data safety monitoring board for the AgNovos Healthcare treatment trial. E.V. is a scientific cofounder of Napa Therapeutics and BHB Therapeutics, serves on the scientific advisory board of Seneque and is a named co-inventor on a patent relating to an epigenetic clock robust to cell composition changes. A.B.M. declares herself chief medical officer of NU and co-founder of Chi Longevity. V.S. is a 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 and Mitrix. S. Horvath 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. Horvath is a named inventor.