| Title: | Structural decomposition enables multi-omics dissection of common and organ-specific aging |
| Journal: | Science China Life Sciences |
| Published: | 8 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42132992/ |
| DOI: | https://doi.org/10.1007/s11427-025-3242-5 |
Publication 20059
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Abstract
Aging exhibits both systemic and organ-specific components, yet existing models struggle to disentangle their shared versus distinct biological determinants at the population level. We present a structural decomposition framework that partitions seven organ-based biological age gaps (BAGs) into a Common BAG (CBAG) and seven Organ-Specific BAGs (OSBAGs) in 501,388 UK Biobank participants. This dual-axis model outperforms undecomposed body/organ BAG approaches in predicting lifespan, healthspan, and organ-specific disease risk. A large-scale aging GWAS identifies 747 novel loci, complemented by integrative proteomic and metabolomic analyses that reveal causal and druggable targets, including CST1. Pathway-guided multi-omics demonstrates a modular aging architecture, with CBAG reflecting cross-tissue regulators (e.g., FOXO3) and OSBAGs capturing organ-restricted effectors (e.g., UMOD). Drug-aging profiling uncovers organ-specific pro-aging effects consistent with known toxicities that are largely missed by undecomposed models. Sex-stratified analyses further reveal divergent molecular trajectories between males and females. All findings are integrated into HONOR, the first open-access atlas for structural aging and multi-omics translation.</p>
16 Authors
- He Huang
- Yi Li
- Qinglin Song
- Liyun Yuan
- Yuqi Yang
- Minwei Zhu
- Renliang Sun
- Yue Hu
- Chenyihang Xiong
- Ting Ni
- Yun Liu
- Andrés Ruiz-Linares
- Guoqing Zhang
- Fan Liu
- Qianqian Peng
- Sijia Wang
1 Application
| Application ID | Title |
|---|---|
| 77803 | Characterization of genetic and phenotypic of obstructive sleep apnea and the potential risk factor of stroke. |
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