Heart-healthy habits can reverse rapid cell aging

The heart health benefits may be related to the positive effects of healthy lifestyle factors on biological aging (the age of the body and its cells), according to a study published in the Journal of the American Heart Association.

“Our results show that, regardless of your actual age, healthy heart habits and managing cardiovascular risk factors are associated with a younger biological age and a reduced risk of heart disease and stroke, cardiovascular mortality, and all-cause mortality,” said Jiangtao Ma, PhD, senior author of the study and an associate professor of nutritional epidemiology and data science at the Friedman School of Nutrition Sciences and Policy at Tufts University in Boston.

This study analyzed a chemical modification process known as DNA methylation, which regulates gene expression and may be one mechanism by which cardiovascular health factors influence cellular aging and mortality risk. DNA methylation levels are the most promising biomarker for assessing biological age. Biological age is determined to some extent by genetic makeup, but it can also be influenced by lifestyle factors and stress.

The researchers examined health data from 5,682 adults (average age 56; 56% women) who participated in the Framingham Heart Study, a large, multigenerational project designed to identify risk factors for heart disease.

Using interviews, physical examinations, and lab tests, all participants were assessed using the American Heart Association's Vital 8 tool. This tool assesses cardiovascular health on a scale of 0 to 100 (with 100 being best) using a combination of four behavioral measures (diet, physical activity, hours of sleep per night, and smoking status) and four clinical measures (body mass index, cholesterol, blood sugar, and blood pressure).

Each participant was also assessed using four tools that estimate biological age based on DNA methylation and a fifth tool that assesses genetic susceptibility to accelerated biological aging. Participants were followed for 11 to 14 years to identify new cardiovascular disease events, cardiovascular mortality, or death from any cause.

The analysis showed:

• For every 13 points increase in the Vital 8 score, the risk of developing cardiovascular disease for the first time decreased by approximately 35%, mortality from cardiovascular disease by 36%, and mortality from all causes by 29%.
• In participants with a genetic predisposition to accelerated biological aging, the Vital 8 score had a greater impact on outcomes, potentially via DNA methylation. DNA methylation explained 39%, 39%, and 78% of the reduction in risk of cardiovascular disease, cardiovascular mortality, and all-cause mortality, respectively.
• Overall, about 20% of the association between Vital 8 scores and cardiovascular outcomes was explained by the influence of cardiovascular health factors on DNA methylation. For participants with higher genetic risk, this association was nearly 40%.

“While there are several DNA methylation-based biological age calculators currently available commercially, we have no clear recommendations on whether people need to know their epigenetic age,” Ma said. “Our message is that everyone should pay attention to the eight factors of heart and stroke health: eat healthy foods, be more active, quit smoking, sleep well, control your weight, and maintain normal cholesterol, blood sugar, and blood pressure levels.”

Randy Foraker, PhD, MS, FAHA, co-author of "The Vital 8: Updating and Improving the American Heart Association's Framework for Cardiovascular Health," said the findings are consistent with previous research.

“We know that modifiable risk factors and DNA methylation are independently associated with cardiovascular disease. This study adds that DNA methylation may mediate the relationship between risk factors and cardiovascular disease,” said Foraker, who is a professor of medicine in the Institute for Informatics, Data Science, and Biostatistics and director of the Center for Population Health Informatics at Washington University School of Medicine in St. Louis, Missouri.

"The study highlights how cardiovascular health can influence biological aging and has important implications for healthy aging and the prevention of cardiovascular disease and possibly other diseases."

Research details, background and design:

• The study analyzed health data from a subgroup of participants who were screened as part of the Framingham Heart Study in the offspring cohort from 2005 to 2008 and in the third-generation cohort from 2008 to 2011.
• Participants were followed for an average of 14 years for the original participants' children and 11 years for the grandchildren.
• Outcomes for analysis included the development of cardiovascular disease (coronary heart disease, myocardial infarction, stroke, or heart failure), death from cardiovascular disease, or death from any cause.
• Results were adjusted for sex, age, and alcohol consumption. Results for all-cause mortality were adjusted for the presence of cancer (excluding non-melanoma skin cancer) or cardiovascular disease at study enrollment. Participants already diagnosed with cardiovascular disease at study enrollment were excluded from the analysis of incident cardiovascular disease.
• Four DNA methylation-based epigenetic age tools were based on established algorithms for assessing DunedinPACE, PhenoAge, DNAmTL and GrimAge. A fifth tool, GrimAge PGS, assessed genetic susceptibility to accelerated biological aging.
• Because the study is an analysis of previously collected health data, it cannot prove a causal relationship between cardiovascular disease risk factors and DNA methylation. In addition, DNA methylation measurements were taken at a single time point, limiting the validity of the mediation effect. The study results are also limited in that the participants were primarily of European descent, so the Vital 8 and genetic aging interaction found in this study may not generalize to people of other races or ethnicities.

"We are now expanding our study to include people of other racial and ethnic groups to further explore the relationship between cardiovascular disease risk factors and DNA methylation," Ma said.

According to the American Heart Association's 2024 statistics, heart disease and stroke claimed more lives in the United States in 2021 than all cancers and chronic lower respiratory diseases combined, and also caused an estimated 19.91 million deaths worldwide.