Integrating the environmental and genetic architectures of aging and mortality
Argentieri MA, Amin N, Nevado-Holgado AJ, Sproviero W, Collister JA, Keestra SM, Kuilman MM, Ginos BNR et al.. Nature medicine, 2025-02-19
Topic: Air pollution and environmental exposures
Plain-language summary
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3-26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5-49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Argentieri, M. A., Amin, N., Nevado-Holgado, A. J., Sproviero, W., Collister, J. A., Keestra, S. M., et al. (2025). Integrating the environmental and genetic architectures of aging and mortality. Nature medicine. https://doi.org/10.1038/s41591-024-03483-9
Vancouver
Argentieri MA, Amin N, Nevado-Holgado AJ, Sproviero W, Collister JA, Keestra SM, et al. Integrating the environmental and genetic architectures of aging and mortality. Nature medicine. 2025. doi:10.1038/s41591-024-03483-9. PMID: 39972219.
BibTeX
@article{argentieri2025-39972219,
author = {Argentieri, M. A. and Amin, N. and Nevado-Holgado, A. J. and Sproviero, W. and Collister, J. A. and Keestra, S. M. and Kuilman, M. M. and Ginos, B. N. R. and others},
title = {{Integrating the environmental and genetic architectures of aging and mortality}},
journal = {Nature medicine},
year = {2025},
doi = {10.1038/s41591-024-03483-9},
pmid = {39972219},
url = {https://doi.org/10.1038/s41591-024-03483-9}
}
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.
Key findings
- To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging.
- These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors.
- Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points.
- Polygenic risk explained a greater proportion of variation (10.3-26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5-49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver.
- Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.
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Study details
- Participants492,567
- Effect size26.2%; 49.4%
- Evidence strengthLow
How this study scored 66/100
Published in a top-tier journal. Scored zero for study design and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 38 of the 58 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 492,567 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39972219) |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 38 of the 58 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
What each of these 20 components measures, and what this score is not →
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