Healthy Lifestyle Linked to Slower Epigenetic Aging, Better Cardiac Outcomes

Image of a heart with a DNA double helix in front of it to indicate cardiovascular disease and the impact of epigenetic aging changes.
Credit: iStock/SvetaP DNA double helix: iStock/Kagenmi

Research led by the Tufts University in Boston shows that having a high combined score of eight heart healthy behaviors is associated with reduced cell aging, as measured by epigenetic biomarkers.

The team also found that a one standard deviation (SD) increase in the score they created was linked to a lower risk of cardiovascular disease and death over the follow up period.

Epigenetic age biomarkers were positively impacted by a healthier lifestyle, with the most pronounced impact seen in those with genetic markers of premature aging.

“Our study findings tell us that no matter what your actual age is, better heart-healthy behaviors and managing heart disease risk factors were associated with a younger biological age and a lower risk of heart disease and stroke, death from heart disease and stroke and death from any cause,” said Jiantao Ma, co-lead investigator and an assistant professor in the division of nutrition epidemiology and data science at the Friedman School of Nutrition Science and Policy at Tufts University in Boston.

Cardiovascular disease has been the leading cause of death in the U.S. for the last 100 years, with around 700,000 people dying from different cardiovascular diseases each year. Lifestyle changes can significantly reduce the chance of people having life changing cardiovascular events such as heart attacks, but such changes can be difficult to implement and measure the impact of.

To try and make the impact of lifestyle changes clearer, the American Heart Association created the “Life Essential 8” (LE8) tool. It measures lifestyle factors related to heart health and creates a score for each person. The factors include diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipid levels, blood glucose levels, and blood pressure.

In the current study, published in the Journal of the American Heart Association, Ma and colleagues calculated the LE8 score for 5682 participants of the Framingham Heart Study. They also calculated scores for four DNA methylation based epigenetic age scores (DunedinPACE Score, PhenoAge, DNAmTL and GrimAge) for the cohort, following the assumption that increased epigenetic age correlates with faster biological aging.

Overall, a one SD increase in the LE8 score among the participants was linked to a 35 percent reduction in risk for cardiovascular disease events over 11–14 years of follow up. Similarly, deaths linked to cardiovascular disease were reduced by 36 percent and all-cause mortality by 29 percent.

Epigenetic aging scores were linked to these reductions in risk, particularly when using the GrimAge and the DunedinPACE scores. The researchers used a polygenic risk score to assess which participants were at higher risk for increased epigenetic age. They found that a higher LE8 score had a greater positive impact in those at higher risk for increase epigenetic age.

“For example, in participants with higher GrimAge polygenic scores (greater than median), the mean proportion of mediation was 39%, 39%, and 78% for the association of the LE8 score with incident cardiovascular disease, cardiovascular disease‐specific mortality, and all‐cause mortality, respectively,” write the authors.

Overall, the researchers estimated a 20 percent impact of epigenetic factors on cardiovascular outcomes, with an increase to 40 percent in those at higher genetic risk for increased epigenetic age.

“We know that modifiable risk factors and DNA methylation are independently associated with cardiovascular disease. What this study adds is that DNA methylation may serve as a mediator between risk factors and cardiovascular disease,” said Randi Foraker, a professor of medicine at the Institute for Informatics, Data Science and Biostatistics and director of the Center for Population Health Informatics, both at Washington University School of Medicine in St. Louis, Missouri, in a press statement.

“The study highlights how cardiovascular health can impact biological aging and has important implications for healthy aging and prevention of cardiovascular disease and potentially other health conditions.”


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