Review

. 2024 Oct;4(10):1372-1383.

doi: 10.1038/s43587-024-00683-3. Epub 2024 Sep 16.

Challenges and recommendations for the translation of biomarkers of aging

Biomarkers of Aging Consortium; Chiara M S Herzog^#¹, Ludger J E Goeminne^#², Jesse R Poganik^#², Nir Barzilai³, Daniel W Belsky⁴, Joe Betts-LaCroix⁵, Brian H Chen^{6

7}, Michelle Chen⁸, Alan A Cohen⁹, Steven R Cummings^{6

7}, Peter O Fedichev¹⁰, Luigi Ferrucci¹¹, Alexander Fleming¹², Kristen Fortney¹³, David Furman^{14

15

16}, Vera Gorbunova¹⁷, Albert Higgins-Chen¹⁸, Lee Hood^{14

19}, Steve Horvath²⁰, Jamie N Justice^{21

22}, Douglas P Kiel^{23

24}, George A Kuchel²⁵, Jessica Lasky-Su²⁶, Nathan K LeBrasseur²⁷, Andrea B Maier^{28

29}, Birgit Schilling¹⁴, Vittorio Sebastiano³⁰, P Eline Slagboom³¹, Michael P Snyder³², Eric Verdin¹⁴, Martin Widschwendter^{1

33

34}, Alex Zhavoronkov⁸, Mahdi Moqri^{35

36}, Vadim N Gladyshev³⁷

Affiliations

¹ European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria.
² Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
⁴ Department of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁵ Retro Biosciences, Inc, San Francisco, CA, USA.
⁶ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
⁷ Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
⁸ Insilico Medicine, Cambridge, MA, USA.
⁹ Department of Environmental Health Sciences, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁰ Gero PTE Ltd, Singapore, Singapore.
¹¹ National Institute on Aging, Baltimore, MD, USA.
¹² Kinexum LLC, Harpers Ferry, WV, USA.
¹³ BioAge Labs, Richmond, CA, USA.
¹⁴ Buck Institute for Research on Aging, Novato, CA, USA.
¹⁵ Stanford 1000 Immunomes Project, Stanford School of Medicine, Stanford, CA, USA.
¹⁶ The National Scientific and Research Council, Austral University, Buenos Aires, Argentina.
¹⁷ Departments of Biology and Medicine, University of Rochester, Rochester, NY, USA.
¹⁸ Department of Psychiatry, Yale University, New Haven, CT, USA.
¹⁹ Phenome Health, Seattle, WA, USA.
²⁰ Altos Labs, San Diego, CA, USA.
²¹ XPRIZE Foundation, Culver City, CA, USA.
²² Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
²³ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Roslindale, MA, USA.
²⁴ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
²⁵ University of Connecticut School of Medicine, @UConnAging, Farmington, CT, USA.
²⁶ Department of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁷ Department of Physical Medicine and Rehabilitation, Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
²⁸ 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.
²⁹ Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³⁰ Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
³¹ Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
³² Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
³³ Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK.
³⁴ Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
³⁵ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. mmoqri@bwh.harvard.edu.
³⁶ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA. mmoqri@bwh.harvard.edu.
³⁷ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. vgladyshev@rics.bwh.harvard.edu.

^# Contributed equally.

PMID: 39285015
PMCID: PMC12262637
DOI: 10.1038/s43587-024-00683-3

Review

Challenges and recommendations for the translation of biomarkers of aging

Biomarkers of Aging Consortium et al. Nat Aging. 2024 Oct.

. 2024 Oct;4(10):1372-1383.

doi: 10.1038/s43587-024-00683-3. Epub 2024 Sep 16.

Authors

Affiliations

¹ European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria.
² Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³ Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
⁴ Department of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁵ Retro Biosciences, Inc, San Francisco, CA, USA.
⁶ San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
⁷ Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
⁸ Insilico Medicine, Cambridge, MA, USA.
⁹ Department of Environmental Health Sciences, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹⁰ Gero PTE Ltd, Singapore, Singapore.
¹¹ National Institute on Aging, Baltimore, MD, USA.
¹² Kinexum LLC, Harpers Ferry, WV, USA.
¹³ BioAge Labs, Richmond, CA, USA.
¹⁴ Buck Institute for Research on Aging, Novato, CA, USA.
¹⁵ Stanford 1000 Immunomes Project, Stanford School of Medicine, Stanford, CA, USA.
¹⁶ The National Scientific and Research Council, Austral University, Buenos Aires, Argentina.
¹⁷ Departments of Biology and Medicine, University of Rochester, Rochester, NY, USA.
¹⁸ Department of Psychiatry, Yale University, New Haven, CT, USA.
¹⁹ Phenome Health, Seattle, WA, USA.
²⁰ Altos Labs, San Diego, CA, USA.
²¹ XPRIZE Foundation, Culver City, CA, USA.
²² Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
²³ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Roslindale, MA, USA.
²⁴ Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
²⁵ University of Connecticut School of Medicine, @UConnAging, Farmington, CT, USA.
²⁶ Department of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁷ Department of Physical Medicine and Rehabilitation, Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
²⁸ 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.
²⁹ Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³⁰ Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
³¹ Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
³² Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
³³ Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK.
³⁴ Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
³⁵ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. mmoqri@bwh.harvard.edu.
³⁶ Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA. mmoqri@bwh.harvard.edu.
³⁷ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. vgladyshev@rics.bwh.harvard.edu.

^# Contributed equally.

PMID: 39285015
PMCID: PMC12262637
DOI: 10.1038/s43587-024-00683-3

Abstract

Biomarkers of aging (BOA) are quantitative parameters that predict biological age and ideally its changes in response to interventions. In recent years, many promising molecular and omic BOA have emerged with an enormous potential for translational geroscience and improving healthspan. However, clinical translation remains limited, in part due to the gap between preclinical research and the application of BOA in clinical research and other translational settings. We surveyed experts in these areas to better understand current challenges for the translation of aging biomarkers. We identified six key barriers to clinical translation and developed guidance for the field to overcome them. Core recommendations include linking BOA to clinically actionable insights, improving affordability and availability to broad populations and validation of biomarkers that are robust and responsive at the level of individuals. Our work provides key insights and practical recommendations to overcome barriers impeding clinical translation of BOA.

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Conflict of interest statement

Competing interests

M.M., V.S., M.P.S. and V.N.G. have filed a patent on measuring cellular aging. C.M.S.H. and M.W. are also affiliated with the Institute for Biomedical Aging Research and the Universität Innsbruck, Austria and C.M.S.H. is an honorary research fellow at the Department of Women’s Cancer, EGA Institute for Women’s Health, University College London, UK. C.M.S.H. and M.W. are shareholders of Sola Diagnostics and named as inventors 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’s Finding Aging biomarkers by Searching existing Trials (FAST) Initiative and on the editorial board of Journals of Gerontology Series A, Biological Sciences, eLife and Experimental Gerontology. D.W.B. is also affiliated with the Child Brain Development Network, the Canadian Institute for Advanced Research and the SocioMed Research Nucleus, Universidad Mayor, Santiago, Chile. D.W.B. is an inventor of DunedinPACE, a Duke University and University of Otago invention licensed to TruDiagnostic, and is consulting CSO and SAB chair of BellSant. A.H.-C. has built epigenetic aging metrics that are licensed by Elysium Health through Yale University. B.H.C. is a full-time employee of FOXO Technologies, which seeks to commercialize epigenetic technologies in the life insurance industry, owns stock in Illumina, the manufacturer of the DNA methylation arrays used for epigenetic BOA and is listed as a co-inventor in filed patents on commercial applications of epigenetic prediction models. A.A.C. is a founder, the president and a majority shareholder at Oken Health. K.F. is the CEO of BioAge Labs. P.O.F. is an employee and a stakeholder in 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 an 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 board of Solarea Bio and has participated in the data safety monitoring board for the AgNovos Healthcare osteoporosis treatment trial. E.V. is a scientific cofounder of Napa Therapeutics and BHB Therapeutics, serves on the scientific advisory board of Seneque and is named as a co-inventor on a patent relating to an epigenetic clock robust to cell composition changes. A.B.M. is the chief medical officer of NU. V.S. is a cofounder, SAB chair and the head of research of Turn Biotechnologies. M.P.S. is a cofounder and a scientific advisor for Personalis, SensOmics, Q Bio, January AI, Fodsel, Filtricine, Protos, RTHM, Iollo, Marble Therapeutics, Crosshair Therapeutics and Mirvie. He is a scientific advisor for Jupiter, Neuvivo, Swaza and Mitrix. S.H. is a founder of the nonprofit Epigenetic Clock Development Foundation, which 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, on which S.H. is a named inventor.

Figures

**Fig. 1 |. Ranking of biomarker criteria.**
Percentages of respondents who graded different criteria for diagnostic, prognostic–predictive and response BOA on a scale from 1 (not important at all) to 5 (extremely important). The mean score is shown for each category. Missing responses are colored gray. n = 29 of 34 invited participants completed the questionnaire.

**Fig. 2 |. Proposed workflow for improved collaboration between researchers and biomarker developers, clinicians and funding agencies to accelerate clinical translation of BOA.**
Close interaction of researchers and biomarker developers with clinicians can help to address clinical needs (for example, specific or optimized biomarkers), and sharing of routine samples by clinicians can help researchers to validate and translate their findings. These interactions will ultimately need to be facilitated by a permissive environment and sufficient funding to perform biomarker profiling.

**Fig. 3 |. Connection of biomarkers to clinical insights and proposed steps for their translational use.**
a, Currently, many BOA are not clearly linked to an actionable insight beyond general health-promoting interventions and may provide lower translational utility for guiding individual healthcare. A key step for future research in BOA will be to link their levels to actionable insights for healthcare. Clinical research could explore whether biomarker levels may enable more targeted screening, different therapies for existing diseases or targeted lifestyle or therapeutic interventions for optimizing health, maximizing the translational utility of a biomarker. b, Successful translation of BOA may use a stepwise approach, building on solid validation (dependent on data sharing). Clinical use can initially be in research settings for participant selection or stratification (for example, to select participants or patients for healthcare screening or intervention based on biological age rather than chronological age). With emerging evidence and better knowledge about individual actionable insights, biomarkers can be leveraged for treatment response monitoring. Ultimately, biomarkers should be part of a paradigm shift in medicine toward optimizing health.

See this image and copyright information in PMC

References

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Challenges and recommendations for the translation of biomarkers of aging

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Challenges and recommendations for the translation of biomarkers of aging

Authors

Affiliations

Abstract

Conflict of interest statement

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Grants and funding

LinkOut - more resources

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