Review

. 2023 Aug 31;186(18):3758-3775.

doi: 10.1016/j.cell.2023.08.003.

Biomarkers of aging for the identification and evaluation of longevity interventions

Mahdi Moqri¹, Chiara Herzog², Jesse R Poganik³; Biomarkers of Aging Consortium; Jamie Justice⁴, Daniel W Belsky⁵, Albert Higgins-Chen⁶, Alexey Moskalev⁷, Georg Fuellen⁸, Alan A Cohen⁹, Ivan Bautmans¹⁰, Martin Widschwendter¹¹, Jingzhong Ding¹², Alexander Fleming¹³, Joan Mannick¹⁴, Jing-Dong Jackie Han¹⁵, Alex Zhavoronkov¹⁶, Nir Barzilai¹⁷, Matt Kaeberlein¹⁸, Steven Cummings¹⁹, Brian K Kennedy²⁰, Luigi Ferrucci²¹, Steve Horvath²², Eric Verdin²³, Andrea B Maier²⁴, Michael P Snyder²⁵, Vittorio Sebastiano²⁶, Vadim N Gladyshev²⁷

Affiliations

¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA; Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
² European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria.
³ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁵ Department of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁶ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁷ Institute of Biogerontology, Lobachevsky University, Nizhny Novgorod, Russia.
⁸ Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany; School of Medicine, University College Dublin, Dublin, Ireland.
⁹ Department of Environmental Health Sciences, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁰ Gerontology Department, Vrije Universiteit Brussel, Brussels, Belgium; Frailty in Ageing Research Department, Vrije Universiteit Brussel, Brussels, Belgium.
¹¹ European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria; Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK; Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
¹² Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹³ Kitalys Institute, Charlottesville, VA, USA.
¹⁴ Tornado Therapeutics, New York, NY, USA.
¹⁵ Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology, Peking University, Beijing, China.
¹⁶ Insilico Medicine Hong Kong, Pak Shek Kok, New Territories, Hong Kong SAR, China.
¹⁷ Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
¹⁸ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹⁹ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
²⁰ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ National Institute on Aging, Baltimore, MD, USA.
²² Altos Labs, San Diego, CA, USA.
²³ Buck Institute for Research on Aging, Novato, CA, USA.
²⁴ Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore, Singapore.
²⁵ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: mpsnyder@stanford.edu.
²⁶ Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: vsebast@stanford.edu.
²⁷ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: vgladyshev@rics.bwh.harvard.edu.

PMID: 37657418
PMCID: PMC11088934
DOI: 10.1016/j.cell.2023.08.003

Review

Biomarkers of aging for the identification and evaluation of longevity interventions

Mahdi Moqri et al. Cell. 2023.

. 2023 Aug 31;186(18):3758-3775.

doi: 10.1016/j.cell.2023.08.003.

Authors

Affiliations

¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA; Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
² European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria.
³ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁵ Department of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁶ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁷ Institute of Biogerontology, Lobachevsky University, Nizhny Novgorod, Russia.
⁸ Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany; School of Medicine, University College Dublin, Dublin, Ireland.
⁹ Department of Environmental Health Sciences, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁰ Gerontology Department, Vrije Universiteit Brussel, Brussels, Belgium; Frailty in Ageing Research Department, Vrije Universiteit Brussel, Brussels, Belgium.
¹¹ European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria; Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK; Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
¹² Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹³ Kitalys Institute, Charlottesville, VA, USA.
¹⁴ Tornado Therapeutics, New York, NY, USA.
¹⁵ Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology, Peking University, Beijing, China.
¹⁶ Insilico Medicine Hong Kong, Pak Shek Kok, New Territories, Hong Kong SAR, China.
¹⁷ Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
¹⁸ Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
¹⁹ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
²⁰ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²¹ National Institute on Aging, Baltimore, MD, USA.
²² Altos Labs, San Diego, CA, USA.
²³ Buck Institute for Research on Aging, Novato, CA, USA.
²⁴ Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Healthy Longevity, @AgeSingapore, National University Health System, Singapore, Singapore.
²⁵ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: mpsnyder@stanford.edu.
²⁶ Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA. Electronic address: vsebast@stanford.edu.
²⁷ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: vgladyshev@rics.bwh.harvard.edu.

PMID: 37657418
PMCID: PMC11088934
DOI: 10.1016/j.cell.2023.08.003

Abstract

With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.

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Conflict of interest statement

Declaration of interests M.M., V.S., M.P.S., and V.N.G. have filed patents on measuring aging. C.H. is affiliated with the Institute for Biomedical Aging Research, Universität 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. and M.W. are shareholders of Sola Diagnostics GmbH and named as inventors on a patent on an epigenetic clock indicative of breast cancer risk. J.N.J. is 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. also 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.W.B. is affiliated with the Child Brain Development Network, Canadian Institute for Advanced Research and SocioMed Research Nucleus, Universidad Mayor, Santiago, Chile. D.W.B. also 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 and is an inventor of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic. A.A.C. is a founder, president, and majority shareholder at Oken Health. I.B. is affiliated with the SOMT University of Physiotherapy, Amersfoort, The Netherlands and is a member of the clinical advisory board of Rejuvenate Biomed. M.W. is affiliated with the Institute for Biomedical Aging Research, Universität Innsbruck, Austria. 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. M.K. is an employee and shareholder of Optispan Inc., a company developing tools to enable science-based personalized and preventative geromedicine. 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. S.H. is also a founder and paid consultant of the nonprofit Epigenetic Clock Development Foundation that licenses patents surrounding epigenetic clocks. A.B.M. is the Chief Medical Officer of NU. V.N.G. is a scientific advisor to Retro and Dior. 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. M.P.S. is also a scientific advisor of Jupiter, Neuvivo, Swaza, and Mitrix. V.S. is co-founder, SAB chair, and head of research of Turn Biotechnologies.

Figures

**Figure 1.. Timeline of key events related to biomarkers of aging and types of common biomarkers of aging.**
a. Timeline of landmark events related to biomarkers of aging. b. Common types and subtypes of biomarkers of aging, based on what they measure. Gray-shaded regions are based on the broad FDA-BEST types of biomarkers framework.

**Figure 2.. Categories of common and potential biomarkers of aging based on their application.**
a. Classification of biomarkers of aging. Gray-shaded regions are based on the broad categories of biomarkers proposed by FDA-BEST. b. Relationships between biomarkers, interventions, and health outcomes, extended from Cummings and Kritchevsky (2022) to include discovery biomarkers and the information feedback loop.

**Figure 3.. Relation between biomarkers of aging and geroprotectors.**
Biomarkers of aging and geroprotectors may appear to have a circular relationship (a). However, development of each is useful to the other: evaluated geroprotectors can be used to develop and benchmark biomarkers of aging, while evaluated biomarkers of aging may be used to predict or test the response to candidate geroprotectors (b).

**Figure 4.. Analytical and clinical validation.**
Adapted from Dobbin et al. (2016) by including details on individual validation steps.

See this image and copyright information in PMC

References

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Biomarkers of aging for the identification and evaluation of longevity interventions

Affiliations

Biomarkers of aging for the identification and evaluation of longevity interventions

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical