Validation of biomarkers of aging

Mahdi Moqri; Chiara Herzog; Jesse R Poganik; Kejun Ying; Jamie N Justice; Daniel W Belsky; Albert T Higgins-Chen; Brian H Chen; Alan A Cohen; Georg Fuellen; Sara Hägg; Riccardo E Marioni; Martin Widschwendter; Kristen Fortney; Peter O Fedichev; Alex Zhavoronkov; Nir Barzilai; Jessica Lasky-Su; Douglas P Kiel; Brian K Kennedy; Steven Cummings; P Eline Slagboom; Eric Verdin; Andrea B Maier; Vittorio Sebastiano; Michael P Snyder; Vadim N Gladyshev; Steve Horvath; Luigi Ferrucci

doi:10.1038/s41591-023-02784-9

Validation of biomarkers of aging

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

Authors

Mahdi Moqri^#^{1

2

3}, Chiara Herzog^#⁴, Jesse R Poganik^#¹, Kejun Ying^{1

5}, Jamie N Justice⁶, Daniel W Belsky⁷, Albert T Higgins-Chen⁸, Brian H Chen⁹, Alan A Cohen¹⁰, Georg Fuellen^{11

12}, Sara Hägg¹³, Riccardo E Marioni¹⁴, Martin Widschwendter^{4

15

16}, Kristen Fortney¹⁷, Peter O Fedichev¹⁸, Alex Zhavoronkov¹⁹, Nir Barzilai²⁰, Jessica Lasky-Su²¹, Douglas P Kiel²², Brian K Kennedy^{23

24}, Steven Cummings^{25

26}, P Eline Slagboom²⁷, Eric Verdin²⁸, Andrea B Maier^{24

29}, Vittorio Sebastiano³, Michael P Snyder², Vadim N Gladyshev³⁰, Steve Horvath³¹, Luigi Ferrucci³²

Affiliations

¹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA.
³ Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA, USA.
⁴ European Translational Oncology Prevention and Screening Institute, Universität Innsbruck, Innsbruck, Austria.
⁵ T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁶ Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁷ Department of Epidemiology, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁸ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁹ Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, CA, USA.
¹⁰ Department of Environmental Health Sciences, Butler Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹¹ Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.
¹² School of Medicine, University College Dublin, Dublin, Ireland.
¹³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹⁴ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
¹⁵ Department of Women's Cancer, EGA Institute for Women's Health, University College London, London, UK.
¹⁶ Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Stockholm, Sweden.
¹⁷ BioAge Labs, Richmond, CA, USA.
¹⁸ Gero PTE, Singapore, Singapore.
¹⁹ Insilico Medicine Hong Kong, Hong Kong SAR, China.
²⁰ Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
²¹ Department of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²² Musculoskeletal Research Center, Hinda and Arthur Marcus Institute for Aging Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
²³ Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
²⁴ 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 San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, USA.
²⁶ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
²⁷ Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
²⁸ Buck Institute for Research on Aging, Novato, CA, USA.
²⁹ Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
³⁰ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. vgladyshev@rics.bwh.harvard.edu.
³¹ Altos Labs, San Diego, CA, USA. shorvath@altoslabs.com.
³² National Institute on Aging, Baltimore, MD, USA. ferruccilu@grc.nia.nih.gov.

^# Contributed equally.

PMID: 38355974
DOI: 10.1038/s41591-023-02784-9

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.

Publication types

Review

MeSH terms

Biomarkers
Consensus
Longevity*
Research Design*

Substances

Biomarkers