Metabolic Age Based on the BBMRI-NL 1 H-NMR Metabolomics Repository as Biomarker of Age-related Disease
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Abstract
Background: The blood metabolome incorporates cues from the environment and the host’s genetic background, potentially offering a holistic view of an individual’s health status. Methods: We have compiled a vast resource of proton nuclear magnetic resonance metabolomics and phenotypic data encompassing over 25 000 samples derived from 26 community and hospital-based cohorts. Results: Using this resource, we constructed a metabolomics-based age predictor (metaboAge) to calculate an individual’s biological age. Exploration in independent cohorts demonstrates that being judged older by one’s metabolome, as compared with one’s chronological age, confers an increased risk on future cardiovascular disease, mortality, and functionality in older individuals. A web-based tool for calculating metaboAge ( metaboage.researchlumc.nl ) allows easy incorporation in other epidemiological studies. Access to data can be requested at bbmri.nl/samples-images-data . Conclusions: In summary, we present a vast resource of metabolomics data and illustrate its merit by constructing a metabolomics-based score for biological age that captures aspects of current and future cardiometabolic health.
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In independent prospective cohorts, accelerated metabolomic age was found to be associated with cardiovascular risk factors, cardiovascular disease risk and all-cause mortality risk.
“In independent prospective cohorts, accelerated metabolomic age was found to be associated with cardiovascular risk factors, cardiovascular disease risk and all-cause mortality risk.”
From Measuring biological age using omics data (2022) · cites this paper as [119]
Another large 1H-NMR biobank study developed a metabolomic clock from 56 reliably measurable metabolites in plasma and evaluated relationships between the metabolomic age gap, cardiovascular phenotypes and mortality.
“Another large 1H-NMR biobank study subsequently developed a metabolomic clock from 56 reliably measurable metabolites in plasma and evaluated relationships between the metabolomic age gap, cardiovascular phenotypes and mortality119.”
From Measuring biological age using omics data (2022) · cites this paper as [119]
Metabolomic clocks have demonstrated lower age prediction accuracy than other omics data types despite training on extremely large sample sizes, and effect sizes for ageing traits have been modest.
“Furthermore, metabolomic clocks have demonstrated lower age prediction accuracy than other omics data types despite training on extremely large sample sizes, and effect sizes for ageing traits have been modest113,116–121.”
From Measuring biological age using omics data (2022) · cites this paper as [119]
van den Akker et al. developed a biobank-scale targeted metabolomic ageing clock that is predictive of mortality and cardiovascular outcomes.
“This study developed a biobank-scale targeted metabolomic ageing clock that is predictive of mortality and cardiovascular outcomes.”
From Measuring biological age using omics data (2022) · cites this paper as [119]
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GlycA, a Biomarker of Low-Grade Inflammation, Is Increased in Male Night Shift Workers
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Network modeling and topology of aging
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Genome‐wide profiles of DNA damage represent highly accurate predictors of mammalian age
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Sebacic Acid as a Potential Age-Related Biomarker of Liver Aging: Evidence Linking Mice and Human
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Self-citationAn aging clock using metabolomic CSFPreprint
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Associations between metabolomic scores and clinical outcomes in hospitalized COVID-19 patients
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Self-citationDevelopment of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA)
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Biological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond
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Self-citationPerspectives in Comparative Biology of Ageing
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Improving our understanding of the biology of aging: findings from the Age-It Research Program
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Self-citationAge‐Dependent Metabolomic Signatures of Dietary Restriction in Mice
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Amino acid-based biological age clock and its implications for human health and aging
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Mass Spectrometry for Lipidomics: Methods and Applications – Aging and A lzheimer's Disease
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NMR metabolomic modelling of age and lifespan: a multi-cohort analysisPreprint
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Exploring geriatricians' perspectives on aging biomarkers: A reflexive thematic analysis
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Self-citationCost-effectiveness of the biological age calculator
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Self-citation
- Authors
- van den Akker, E. B., Trompet, S., Barkey Wolf, J. J. H., Beekman, M., Suchiman, H. E. D., Deelen, J., Asselbergs, F. W., Boersma, E., Cats, D., Elders, P. M., Geleijnse, J. M., Ikram, M. A., Kloppenburg, M., Mei, H., Meulenbelt, I., Mooijaart, S. P., Nelissen, R. G. H. H., Netea, M. G., Penninx, B. W. J. H., Slofstra, M., Stehouwer, C. D. A., Swertz, M. A., Teunissen, C. E., Terwindt, G. M., ‘t Hart, L. M., van den Maagdenberg, A. M. J. M., van der Harst, P., van der Horst, I. C. C., van der Kallen, C. J. H., van Greevenbroek, M. M. J., van Spil, W. E., Wijmenga, C., Zhernakova, A., Zwinderman, A. H., Sattar, N., Jukema, J. W., van Duijn, C. M., Boomsma, D. I., Reinders, M. J. T., & Slagboom, P. E.
- Affiliations
- Department of Molecular Epidemiology (E.B.v.d.A., J.J.H.B.W., M.B., H.E.D.S., J.D., D.C., H.M., I.M., L.M.‘t.H., P.E.S.)
- Leiden University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Erasmus MC (NL)
- Department of General Practice and Elderly Care Medicine (P.M.E.), VU University Medical Center, the Netherlands.
- University of Bonn (DE)
- University of Groningen (NL)
- University Medical Center Groningen (NL)
- Department of Human Genetics (A.M.J.M.v.d.M.), Leiden University Medical Center, the Netherlands.
- Department of Cardiology (P.v.d.H.), University Medical Center Groningen, the Netherlands.
- Department of Critical Care (I.C.C.v.d.H.), University Medical Center Groningen, the Netherlands.
- Department of Internal Medicine, Maastricht University Medical Center, the Netherlands (C.D.A.S., C.J.H.v.d.K., M.M.J.v.G.).
- Department of Rheumatology and Clinical Immunology (W.E.v.S.), University Medical Center Utrecht, the Netherlands.
- Amsterdam UMC Location University of Amsterdam (NL)
- Department of Epidemiology (M.A.I., C.M.v.D.), Erasmus Medical Center, Rotterdam, the Netherlands.
- ORCID
- van den Akker, Erik B.
- Trompet, Stella
- Beekman, Marian
- Suchiman, H. Eka D.
- Deelen, Joris
- Asselbergs, Folkert W.
- Boersma, Eric
- Cats, Davy
- Elders, Petra M.
- Geleijnse, J. Marianne
- Ikram, M. Arfan
- Mei, Haillang
- Meulenbelt, Ingrid
- Mooijaart, Simon P.
- Nelissen, Rob G.H.H.
- Penninx, Brenda W.J.H.
- Stehouwer, Coen D.A.
- Swertz, Morris A.
- Teunissen, Charlotte E.
- Terwindt, Gisela M.
- ‘t Hart, Leen M.
- van der Harst, Pim
- van der Horst, Iwan C.C.
- van der Kallen, Carla J.H.
- van Spil, W. Erwin
- Wijmenga, Cisca
- Zhernakova, Alexandra
- Zwinderman, Aeilko H.
- Sattar, Naveed
- Jukema, J. Wouter
- van Duijn, Cornelia M.
- Boomsma, Dorret I.
- Reinders, Marcel J.T.
- Slagboom, P. Eline
- Venue
- Circulation: Genomic and Precision Medicine
- Published
- 2020-10
- Volume
- 13
- Issue
- 5
- Pages
- 541-547
- ISSN
- 2574-8300 (ISSN-L)
- OpenAlex
- W3049304614
- Cited by
- 109
- References
- 22
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 35 · 2023: 17 · 2022: 12 · 2021: 8 · 2020: 2 · 2019: 1
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Genomic and Precision Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Research Publications (Maastricht University) (acceptedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (acceptedVersion, other-oa)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- VU Research Portal (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb (2001 D 032)
- Pfizer (115372)
- Sanofi
- Health Foundation Limburg (31O.041)
- National Institute for Health and Care Research (115372, FP7/2007–2013)
- European Commission (QLG2-CT-2002-01254, 184.021.007, 018947, 602633, FP7/2007-2011, 2007–2013, 911-09-032, 230374, FP7 2007-2013, 201413, 480-04-004, 480-15-001/674, FP7/2007, 259679, 01254, 601456, 115372, 305507, 400-05-717, LSHG-CT-2006-018947)
- University of Glasgow
- Universiteit Leiden (050-060-810, 05040202, 10‐000‐1002)
- Rijksuniversiteit Groningen (10‐000‐1002)
- ZonMw (Addiction‐31160008, Middelgroot‐911‐09‐032, 985-10-002, 400‐05‐717, 480-15-001/674, 733051021, 56-464-14192, 184.021.007, 904-61-193, 911‐09‐032, 91816631, grant number 10-000-1002, 904-61-090, 05040202, 91816631/528, 31160008, 90700217, 480‐04‐004, 10‐000‐1002, 91711319, 050-060-810)
- Universiteit van Amsterdam
- Erasmus Universiteit Rotterdam
- Technische Universiteit Delft
- Radboud Universiteit
- Vrije Universiteit Amsterdam (FP7/2007-2013)
- Universiteit Maastricht
- College voor Zorgverzekeringen
- Erasmus Medisch Centrum (050-060-810)
- Diabetes Fonds (98.901, 940-35-034)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (184021007, 10-000-1002, 400‐05‐717, 050.060.810, 904-61-193, 904-61-090, 917.11.319, FP7 2007-2013, NWO 480‐15‐001/674, 311-60008, 940–35–034, MagW/ZonMW grants 904-61-090, 56‐464‐14192, 98.901, 918-56-602, Addiction-31160008, 230374, SenterNovem IGE05007, Spinozapremie 56-464-14192, 602633, 911-09-032, 985-10002, Middelgroot-911-09-032, 14192, 91816631/528, 05040202, 480-04-004, 480-15-001, 904-61-090, 985-10-002, 480‐15‐001/674, NWO 184.021.007)
- GGZ inGeest
- GGZ Friesland
- GGZ Drenthe
- Novo Nordisk
- Maastricht Universitair Medisch Centrum
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Radboud Universitair Medisch Centrum
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Hersenstichting
- Internationale Stichting Alzheimer Onderzoek
- Stichting De Weijerhorst (31O.041)
- Alzheimer Nederland
- Centre for Medical Systems Biology (05040202, 480-04-004)
- Amsterdam Neuroscience
- Dutch Arthritis Association (05040202, 050-060-810, DAA_10_1-402)
- National Institutes of Health (R01D0042157-01A, FP7/2007-2013, 184.021.007, QLG2-CT-2002-01254, NWO 184.021.007, 480-15-001/674, 1r01mh081802-01, 400-05-717)
- U.S. Public Health Service (R01D0042157‐01A)
- Wageningen University and Research
- European Regional Development Fund (FP7/2007‐2013, 2007 – 2013, NWO 184.021.007, 31O.041)
- CARIM School for Cardiovascular Diseases, Universiteit Maastricht
- Netherlands Heart Institute (200T401)
- National Heart, Lung, and Blood Institute (R01HL076200)
- National Institute of Mental Health (MH068457, MH-081802, HEALTH-F4-2007-201413, MH089951, U24MH068457, MH068457-06, NIMH U24 MH068457-06, RC2MH089951)
- Cilag
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- metabolic age, biological age, blood metabolome, age-related diseases, cardiovascular risk, mortality, functional capacity, age prediction, 1H NMR metabolomics, cardiometabolic health, web-based calculator
- MeSH terms
- Aging, Cardiovascular Diseases, Humans, Netherlands, Risk Factors, User-Computer Interface, Biomarkers, Proportional Hazards Models, Metabolomics, Proton Magnetic Resonance Spectroscopy
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