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Organ-specific proteomic aging clocks predict disease and longevity across diverse populations
Yunhe Wang, Sihao Xiao, Bowen Liu, Rongtao Jiang, Yuxi Liu, Yian Hang, Li Chen, Runsen Chen et al.. Nature Aging, 2025-11-26
Topic: Brain proteins, microglia and lab models
Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly linked to mortality. Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the GABBR1 and ECM1 genes, and brain structure. Distinct organ-specific pathogenic pathways were identified, with the brain and artery clocks linking synaptic loss, vascular dysfunction and glial activation to cognitive decline and dementia. The brain aging clock further stratified Alzheimer's disease risk across APOE haplotypes, and a super-youthful brain appears to confer resilience to APOE4. Together, proteomic organ aging clocks provide a biologically interpretable framework for tracking aging and disease risk across diverse populations.
Key findings
- Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the GABBR1 and ECM1 genes, and brain structure.
Why it matters
Using plasma proteomics, this study built organ-specific aging clocks and found that brain aging was linked to cognitive decline and dementia and could stratify Alzheimer's disease risk across APOE types. It is a risk-prediction framework and does not test any treatment, cure, or prevention.
Study details
- Participants43,616
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 43,616 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 32 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Andrew T. Chan: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 14 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41299092) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wang, Y., Xiao, S., Liu, B., Jiang, R., Liu, Y., Hang, Y., et al. (2025). Organ-specific proteomic aging clocks predict disease and longevity across diverse populations. Nature Aging. https://doi.org/10.1038/s43587-025-01016-8
Vancouver
Wang Y, Xiao S, Liu B, Jiang R, Liu Y, Hang Y, et al. Organ-specific proteomic aging clocks predict disease and longevity across diverse populations. Nature Aging. 2025. doi:10.1038/s43587-025-01016-8. PMID: 41299092.
BibTeX
@article{wang2025-41299092,
author = {Wang, Yunhe and Xiao, Sihao and Liu, Bowen and Jiang, Rongtao and Liu, Yuxi and Hang, Yian and Chen, Li and Chen, Runsen and others},
title = {{Organ-specific proteomic aging clocks predict disease and longevity across diverse populations}},
journal = {Nature Aging},
year = {2025},
doi = {10.1038/s43587-025-01016-8},
pmid = {41299092},
url = {https://doi.org/10.1038/s43587-025-01016-8}
}
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