| Title: | Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk |
| Journal: | Nature Communications |
| Published: | 26 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40419465/ |
| DOI: | https://doi.org/10.1038/s41467-025-59964-z |
| URL: | https://www.nature.com/articles/s41467-025-59964-z.pdf |
Publication 15231
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Abstract
Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25<r < 0.42). Crucially, including composite metabolites (e.g. sums or ratios of raw metabolites) results in poor generalizability to independent test data due to multicollinearity. Genome-wide associations identify 405 MetBAG-locus pairs (P < 5 × 10−8/5). Using SBayesS, we estimate the SNP-based heritability (0.09<hSNP2$${h}_{{SNP}}^{2}$$ < 0.18), negative selection signatures (−0.93 < S < −0.76), and polygenicity (0.001<Pi < 0.003) for the 5 MetBAGs. Genetic correlation and Mendelian randomization analyses reveal potential causal links between the 5 MetBAGs and cardiometabolic conditions (e.g., metabolic disorders and hypertension). Integrating multi-organ and multi-omics features improves disease category and mortality predictions. The 5 MetBAGs extend existing biological aging clocks to study human aging and disease across multiple biological scales. All results are publicly available at https://labs-laboratory.com/medicine/.</p>
16 Keywords
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cardiovascular Diseases
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Metabolic Diseases
- Metabolome
- Metabolomics
- Middle Aged
- Polymorphism, Single Nucleotide
- United Kingdom
6 Authors
- Filippos Anagnostakis
- Sarah Ko
- Mehrshad Saadatinia
- Jingyue Wang
- Christos Davatzikos
- Junhao Wen
1 Application
| Application ID | Title |
|---|---|
| 35148 | iSTAGING (Imaging-based coordinate SysTem for AGing and NeurodeGenerative diseases) |
Enabling scientific discoveries that improve human health