A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank
The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention.
Authors
- Xingxing Jian (ORCID: https://orcid.org/0000-0003-3587-662X)
- Julian Mutz (ORCID: https://orcid.org/0000-0001-5308-1957)
- Kun Xia (ORCID: https://orcid.org/0000-0001-8090-6002)
- Jinchen Li (ORCID: https://orcid.org/0000-0001-5522-806X)
- Yixiao Zhu
- Beisha Tang (ORCID: https://orcid.org/0000-0003-2120-1576)
- Bin Li (ORCID: https://orcid.org/0000-0002-8442-0154)
- Zheng Wang (ORCID: https://orcid.org/0000-0002-8388-6139)
- Guihu Zhao (ORCID: https://orcid.org/0000-0003-4033-1843)
- Yijing Wang (ORCID: https://orcid.org/0000-0002-5267-5697)
- Qiao Zhou (ORCID: https://orcid.org/0000-0001-5929-5438)
- Jian Qiu (ORCID: https://orcid.org/0000-0001-7873-0722)
- Shiyu Zhang (ORCID: https://orcid.org/0000-0003-3863-4685)
Institutions
- Central South University (CN)
- Hunan University (CN)
- King's College London (GB)
- National Clinical Research (US)
- First Affiliated Hospital of University of South China (CN)
- Xiangya Hospital Central South University (CN)
- University of South China (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-15
- DOI
- https://doi.org/10.1038/s41467-024-52310-9
- Citations
- 79
- Primary Topic
- Metabolomics and Mass Spectrometry Studies
- Type
- article
- Field-Weighted Citation Impact
- 18.47
Funders
- South London and Maudsley NHS Foundation Trust
- National Institute for Health and Care Research
- King's College London
- National Natural Science Foundation of China
- Central South University
- NIHR Maudsley Biomedical Research Centre
- Fundamental Research Funds for the Central Universities