Lifestyle and environmental factors affect health and ageing more than our genes

A new study led by researchers from Oxford Population Health has shown that a range of environmental factors, including lifestyle (smoking and physical activity), and living conditions, have a greater impact on health and premature death than our genes.

The researchers used data from nearly half a million UK Biobank participants to assess the influence of 164 environmental factors and genetic risk scores for 22 major diseases on ageing, age-related diseases, and premature death. The study is published today in Nature Medicine.

Key findings

• Environmental factors explained 17% of the variation in risk of death, compared to less than 2% explained by genetic predisposition (as we understand it at present);
• Of the 25 independent environmental factors identified, smoking, socioeconomic status, physical activity, and living conditions had the most impact on mortality and biological ageing;
• Smoking was associated with 21 diseases; socioeconomic factors such as household income, home ownership, and employment status, were associated with 19 diseases; and physical activity was associated with 17 diseases;
• 23 of the factors identified are modifiable;
• Early life exposures, including body weight at 10 years and maternal smoking around birth, were shown to influence ageing and risk of premature death 30-80 years later;
• Environmental exposures had a greater effect on diseases of the lung, heart and liver, while genetic risk dominated for dementias and breast cancer.

Professor Cornelia van Duijn, St Cross Professor of Epidemiology at Oxford Population Heath and senior author of the paper, said ‘Our research demonstrates the profound health impact of exposures that can be changed either by individuals or through policies to improve socioeconomic conditions, reduce smoking, or promote physical activity.

‘While genes play a key role in brain conditions and some cancers, our findings highlight opportunities to mitigate the risks of chronic diseases of the lung, heart and liver which are leading causes of disability and death globally. The early life exposures are particularly important as they show that environmental factors accelerate ageing early in life but leave ample opportunity to prevent long-lasting diseases and early death.’

The authors used a unique measure of ageing (a new “ageing clock”) to monitor how rapidly people are ageing using blood protein levels. This enabled them to link environmental exposures that predict early mortality with biological ageing. This measure was previously shown to detect age-related changes, not only in the UK Biobank but also in two other large cohort studies from China and Finland.

Dr Austin Argentieri, lead author of the study at Oxford Population Health and Research Fellow at Massachusetts General Hospital, said ‘Our exposome approach allowed us to quantify the relative contributions of the environment and genetics to ageing, providing the most comprehensive overview to date of the environmental and lifestyle factors driving ageing and premature death. These findings underscore the potential benefits of focusing interventions on our environments, socioeconomic contexts, and behaviours for the prevention of many age-related diseases and premature death.’

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, added ‘Your income, postcode and background shouldn’t determine your chances of living a long and healthy life. But this pioneering study reinforces that this is the reality for far too many people.

‘We have long known that risk factors such as smoking impact our heart and circulatory health, but this new research emphasises just how great the opportunity is to influence our chances of developing health problems, including cardiovascular disease, and dying prematurely. We urgently need bold action from Government to target the surmountable barriers to good health that too many people in the UK are facing.’

The research shows that whilst many of the individual exposures identified played a small part in premature death, the combined effect of these multiple exposures together over the life course (referred to as the exposome) explained a large proportion of premature mortality variation. The insights from this study pave the way for integrated strategies to improve the health of ageing populations by identifying key combinations of environmental factors that shape risk of premature death and many common age-related diseases simultaneously.

Professor van Duijn said ‘Studies on environmental health have tended to focus on individual exposures based on a specific hypothesis. While this approach has seen many successes, the method has not always yielded reproducible and reliable findings. Instead, we have followed a ‘hypothesis free’ exposome approach and studied all available exposures to find the major drivers of disease and death.

‘We have made a big leap forward in understanding how to provide accurate evidence on the causes and consequences of age-related diseases by combining novel computational methods with clinical and epidemiological knowledge to explore the interplay between multiple exposures. In an ever-changing environment, it is critical that we combine these techniques with novel advances in smart technology to monitor lifestyle and environment, as well as with biological data, to understand the impact of the environment over time. There are a lot of questions still to be answered related to diet, lifestyle, and exposure to new pathogens (such as bird flu and COVID-19) and chemicals (think of pesticides and plastics), and the impact of environmental and genetic factors in different populations.’

The study was led by researchers from Oxford Population Health in collaboration with researchers from the Departments of Psychiatry and Anthropology at the University of Oxford; Massachusetts General Hospital, and the Broad Institute, Boston; the University of Amsterdam; Erasmus University, Rotterdam; and the University of Montpellier.

Technical support was provided by the China Kadoorie Biobank team.

Editor’s notes

Talk to the authors at a press briefing coordinated by the UK Science Media Centre on Tuesday 18 February at 12:00 noon GMT. To join the briefing, please email Fiona Lethbridge. 

For further information or interviews, please email Anne Whitehouse, Director of Communications and Public Engagement, Oxford Population Health, tel +44(0)1865 289474.

Article title: Integrating the environmental and genetic architectures of aging and mortality

DOI:10.1038/s41591-024-03483-9 NMED-A126194

Post-publication link nature.com/articles/s41591-024-03483-9

For more information on the proteomic ageing clock, see the Oxford Population Health website and Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations. Nat Med 30, 2450–2460 (2024).

About Oxford Population Health

Oxford Population Health (the Nuffield Department of Population Health) is a world-leading research institute, based at the University of Oxford that investigates the causes and prevention of disease. The department has around 1000 staff, students and academic visitors working in a number of world-renowned population health research groups, including the Cancer Epidemiology Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, and the National Perinatal Epidemiology Unit, and other groups working on public health, health economics, -omics, ethics and health record linkage. It is also a key partner in the Oxford University Big Data Institute.