A groundbreaking study by Argentieri and colleagues (2025) published in Nature Medicine revealed that our lifestyle choices and environment impact mortality more strongly than our genetic makeup. Analyzing data from nearly half a million participants in the UK Biobank, researchers examined genetic markers and over 100 environmental variables to understand their relative contributions to 22 major diseases. The study incorporated an innovative approach by measuring biological aging through blood protein analysis in 45,000 individuals, establishing the "proteomic age gap" — the difference between one's biological and chronological age. This measurement was a powerful predictor of mortality risk and age-related conditions such as cognitive decline and frailty.
The research quantified this disparity strikingly: environmental and lifestyle factors accounted for 17% of disease mortality risk, while genetics contributed just 2%. Among the environmental factors, smoking emerged as the most harmful, linked to 21 different diseases, followed by socioeconomic status (influencing 19 diseases) and physical inactivity (connected to 17 diseases).
The lungs, heart, and liver were most vulnerable to environmental influences, while genetics played a stronger role in certain cancers (breast, ovarian, and prostate) and dementia. Importantly, the researchers discovered that environmental influences begin early, with factors like maternal smoking and childhood weight having health consequences that extend decades into the future.
Why This Disease Mortality Study Matters
The study identified risk factors and highlighted protective elements that promote longevity, including partnership status, employment, and financial stability. These modifiable factors represent opportunities for intervention at both individual and policy levels, including efforts to reduce smoking rates, encourage physical activity, and address socioeconomic inequalities.
Reference
Argentieri, M. A., Amin, N., Nevado-Holgado, A. J., Sproviero, W., Collister, J. A., Keestra, S. M., Kuilman, M. M., Ginos, B. N. R., Ghanbari, M., Doherty, A., Hunter, D. J., Alvergne, A., & van Duijn, C. M. (2025). Integrating the environmental and genetic architectures of aging and mortality. Nature Medicine, 10.1038/s41591-024-03483-9. Advance online publication. https://doi.org/10.1038/s41591-024-03483-9
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