New research has shed light on the significant role that environmental factors play in aging and premature death, challenging previous beliefs about genetic influences.
A study published in Nature Medicine explores how genetics and environment interact, providing insights into disease prevention strategies.
Human aging is a complex process marked by biological and subclinical changes that begin in mid-life, typically between ages 40 to 60. Studies have shown that environmental factors can nearly double the risk of premature mortality.
The exposome, encompassing all life-time environmental exposures, has been studied extensively for its impact on aging. However, fewer large-scale studies have examined independent associations between the exposome and population-level health outcomes like age-related diseases.
About the Study
This study compares genetic and environmental influences on premature mortality and major age-related diseases using a robust pipeline to evaluate reverse causation and residual confounding. The research utilized data from 436,891 participants in England, with an additional validation set of 55,676 participants from Scotland and Wales.
Over 12.5 years of follow-up resulted in 31,716 deaths recorded across various age-related diseases. The study identified 25 independent exposures linked to proteomic aging, premature mortality, age-related diseases, and biochemical markers of aging.
Key Environmental Contributors
The primary environmental contributors to aging and death were found to be socioeconomic status and deprivation, smoking habits, the number of household vehicles, physical activity levels, ethnicity, living arrangements (with or without a partner), sleep patterns, mental health wellness, and physical wellness. Additionally,
- Maternal smoking around birth
- Height and body size at age 10
were associated with premature death.
Socioeconomic Status and Smoking Key Factors:
A significant link was found between socioeconomic status, specifically living in council housing versus home ownership, smoking frequency, physical tiredness, and early mortality. Cox proportional hazards models were used to identify how these exposures impact age-related diseases leading to premature death.
Interconnected Environmental Biomarkers
Each of the 25 identified environmental exposures was connected with a wide range of biomarkers linked to various organ systems and mechanistic pathways. On average, each exposure was associated with 20 out of 25 aging biomarkers. For instance,
- Smoking status
- Ethnicity
were connected with all 25 biomarkers.
Genetics vs Environment in Disease:
About two-thirds of mortality-associated exposures were not associated with proteomic aging, suggesting a high variability across many disorders. For example,
- Diseases like dementia and macular degeneration, Alzheimer’s disease, and some cancers (e.g., prostate and breast) are more influenced by polygenic risk.
However, diseases such as rheumatoid arthritis, ischemic heart disease, kidney disorders are significantly impacted by environmental factors.
Conclusions:
This study highlights the importance of large biobanks in understanding how genetic and environmental factors interact to influence aging and premature mortality. It underscores potential for interventions focusing on the environment to prevent early death and age-related diseases. The exposome shapes distinct patterns of disease risk, irrespective of polygenic risks.
Future Research:
Causal modeling studies are needed in future research to identify specific environmental exposures that can help in prevention strategies.
