Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 8081 |
| Number of pages | 1 |
| Journal | Nature Communications |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 15 Sept 2024 |
Keywords
- Humans
- Aging/genetics
- United Kingdom/epidemiology
- Male
- Genome-Wide Association Study
- Biological Specimen Banks
- Female
- Metabolomics/methods
- Aged
- Middle Aged
- Biomarkers/metabolism
- Mendelian Randomization Analysis
- Magnetic Resonance Spectroscopy
- Metabolome
- Longitudinal Studies
- Whole Genome Sequencing
- Adult
- Aged, 80 and over
- UK Biobank