New research shows that environmental factors, from smoking to socio -economic status, have a stronger influence on aging and premature death than genetics – which translates our understanding of disease prevention.
Study: Integration of the environmental and genetic architectures of aging and mortality. Image Credit: Shutterstock AI Generator / Shutterstock.com
A recent Nature Medicine Study compares the relative contributions of genetics and the environment with aging and premature mortality.
The impact of environmental and genetic factors on the aging of man
Human aging is a complex process associated with biological and subclinical changes that start in the middle of life, usually between 40 and 60 years old. Various studies have reported that non-genetic environmental factors can speed up the aging process and increase the risk of early mortality by almost dual-time.
The exposome refers to the total set of interconnected environmental bastles during the life of an individual. Despite earlier exposome-wide study designs that offer crucial insights into how the environmental exposure influences the aging, few large-scale studies have investigated potential independent associations between the exposome, population level mortality and age-related illness.
About the study
The current study compares the contributions of the genome and exposome to premature mortality and large age -related diseases using a robust pipeline that has been developed to evaluate reverse causal connection and remaining confounding.
Initially, an exposome-wide analysis was performed using population-based data from the United Kingdom of the British Biobank to systematically determine exposures that are independently linked to the risk of premature mortality. Subsequently, a phenoom-wide analysis was performed for each mortality-associated exposure to remove expansions that are sensitive to confusion and crime.
A total of 176 unique exposures were available, both for men and women. Expositions only associated with a proteomic aging clock were considered, because this made it possible to identify factors that were exclusively related to the aging process. The effect of the identified exhibitions was assessed with regard to the beginning of 25 large age -related diseases.
Genetics versus environment: important contributors to aging and death
The current study included a total of 436,891 UKB participants from England. An extra 55,676 UKB participants from Scotland and Wales were used as a validation set for definitive multivariable disease models. After a median of 12.5 years of follow-up, 31,716 deaths were registered of all causes.
The study cohort showed several age -related diseases, including brain cancer and osteoarthritis. Multiple step-by-step analyzes were carried out, including an exposome-wide association study (XWAS), Fenoom-wide association study (Phewas) and hierarchical clustering in a single COX model. These analyzes identified 25 independent exposures associated with proteomic aging, premature mortality, age -related diseases and biochemical markers of aging.
The primary contributors to aging and premature death were socio -economic status and hardship, smoking, the number of household vehicles, physical activity, ethnicity, living with a partner, sleep, as well as mental and physical well -being.
Maternal smoking near birth time, as well as length and body size at the age of 10, were also associated with premature death. Among these factors, current smokers, people who are more often tired to feel tired, and those who live in the municipality compared to home ownership, mainly associated with premature death and aging.
COX models for proportional dangers were used to determine whether the identified exposures increased the risk of developing age-related diseases that contribute to premature mortality. Each of the 25 exposures was associated with a wide range of aging biomarkers related to various organ systems and mechanistic routes.
Many interconnected factors connect the environmental architecture of mortality and aging, which has not contributed significantly to the outcome individually. On average, every exposure was associated with 22 of the 25 biomarkers. For example, smoking status and ethnicity were linked to all 25 biomarkers.
Metabolic risk factors of common diseases, such as obesity and hypertension, were transversal associated with most studied exposures. That is why many age-specific diseases share a common environmental etiology that can contribute to life expectancy, including premature death.
About 66% of the mortality-associated exposures were not associated with proteomic aging.
The genome and environmental factors have attributed a high variability for many disorders. Certain diseases, such as dementia due to all causes and macular degeneration, Alzheimer’s disease, and certain cancers, including those of the prostate and chest, were mainly influenced by the polygene risk. However, diseases such as rheumatoid arthritis, ischemic heart disease and kidney diseases were considerably influenced by the exposome.
Conclusions
The current study emphasizes the importance of large biobanks to offer crucial insights into the interplay between genetic and environmental bolts in aging and premature mortality. These findings emphasize the potential of environmental interventions to prevent premature mortality and the development of countless age -related diseases.
The exposome is different patterns of disease and mortality risk, regardless of the risk of polygene diseases. “
In the future, causal modeling studies are needed to identify specific investments of interest.
Journal Reference:
- Argentieri, Ma, Amin, N., Nevado-Holgado, AJ, et al .. (2025) Integration of the environmental and genetic architectures of aging and mortality. Nature Medicine; 1-10. DOI: 10.1038/S41591-024-03483-9