It’s impossible to predict when you’re going to die. But if you’re aiming for a long and healthy life, it pays to worry less about your genes—which you can’t change anyway—and more about your lifestyle and surroundings. That’s the conclusion of a new study in Nature Medicine that takes a broad look at the longstanding environment-vs.-heredity debate, and comes down firmly in the environment camp.
The work was based on data from more than 490,000 people, all of whom are registered with the UK Biobank, a massive collection of participants’ detailed medical histories including gene sequencing; MRIs; blood, urine, and saliva samples; family health stories; and more. Researchers used this rich data to study the influence of genetics and more than 100 environmental factors on the risk of 22 diseases that make up most of the major causes of death.
To do that, they focused especially closely on a subset of 45,000 people whose blood samples had been subjected to what is known as proteomic profiling: an analysis of thousands of proteins that help determine physical age compared to calendar age.
“We can get an estimation of how quickly or slowly each participant is aging biologically compared to their chronological age,” says lead author Austin Argentieri, a research fellow at Massachusetts General Hospital. “This is referred to as the ‘proteomic age gap,’ since it’s the gap in years between protein-predicted age and chronological age. [It] is a very strong predictor of mortality…[and] it is also associated strongly with many important aging traits like frailty and cognitive function.”
Just knowing that age gap, of course, is only part of the picture. Equally important is the cause of that gap. To help determine that, the researchers analyzed people’s many environmental and behavioral exposures that contribute to disease and biological age. These factors include income, neighborhood, employment status, marital status, education, and diet, as well as whether people smoke or exercise regularly.
To cover the genetic side, researchers analyzed people’s genomes, looking for genetic markers associated with the 22 key diseases. In addition, they noted which individuals had already developed any of those diseases.
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The results were striking. Environment and lifestyle accounted for 17% of people’s disease-related risk of dying, compared to just 2% for genetics. Of the various environmental exposures, smoking was the riskiest behavior, linked to 21 diseases; socioeconomic factors such as household income, neighborhood, and employment status were associated with 19 diseases; and a lack of physical activity was linked to 17 diseases. Environmental exposures had the greatest impact on lung, heart, and liver disease, while genetics played the greatest role in determining a person’s risk of breast, ovarian, and prostate cancers, plus dementia.
Disturbingly, the study also revealed that the influence of environment begins early in life. High or low body weight as young as age 10 and maternal smoking around birth were found to affect health and mortality many decades later.
The investigators looked not just at the factors that increase the risk of dying from one of the chronic diseases, but also those that decrease it. Of those, living with a partner, being employed, and being financially comfortable had the greatest effect on extending lifespan.
“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,” said senior author Cornela van Duijn, professor of epidemiology at Oxford Population Health, in a statement that accompanied the release of the paper.
The researchers do not see the current study, for all its sweep, to be the end of their work. In the future, they recommend looking more closely at multiple factors, including diet, exposure to novel pathogens such as COVID-19 and bird flu, and environmental factors such as plastics and pesticides. All of those are potentially powerful—but understudied—influences on lifespan.