Heart-healthy behaviors could reverse rapid cellular aging

“Our findings show that engaging in heart-healthy behaviors and managing heart disease risk factors is associated with younger biological age, lower risk of heart disease and stroke, and lower risk of death from heart disease, stroke, and all-cause mortality, regardless of chronological age,” said Jiantao Ma, PhD, assistant professor in the Department of Nutrition Epidemiology and Data Science at the Friedman School of Nutrition Science and Policy at Tufts University, Boston, and lead author of the study.

This study analyzed whether a chemical modification process called DNA methylation, which controls gene expression, is one of the mechanisms by which cardiovascular health factors influence cellular aging and mortality risk. DNA methylation levels are the most promising biomarkers to estimate biological age, which is determined to some extent by genetic makeup but can also be influenced by lifestyle factors and stress.

The researchers looked at health data from 5,682 adults (mean age 56 years; 56% of participants were women) who participated in the Framingham Heart Study, a large ongoing multigenerational research project aimed at identifying risk factors for heart disease. Using interviews, physical examinations, and laboratory tests, all participants were assessed using the American Heart Association's Life's Essential 8 tool, which combines four behavioral measures (dietary intake, physical activity, number of hours of sleep per night, and smoking status) and four clinical measures (body mass index, cholesterol, blood glucose, and blood pressure) to score cardiovascular health between 0 and 100 (100 being the best). Each participant was also assessed by four tools that estimate biological age based on DNA methylation and a fifth tool that assesses genetic propensity for accelerated biological aging. Participants were followed for 11 to 14 years for new-onset cardiovascular disease, cardiovascular death, or death from any cause.

The analysis revealed the following:

• For every 13-point increase in an individual's Life's Essential 8 score, there was an approximately 35% reduction in the risk of a first-time cardiovascular event, a 36% reduction in death from cardiovascular disease, and a 29% reduction in death from any cause.
• For participants whose genetic risk profile made them more likely to experience accelerated biological age, the Life's Essential 8 score could have a significant impact on outcomes via DNA methylation, with DNA methylation reducing the risk of cardiovascular disease, cardiovascular death, and all-cause mortality by 39%, 39%, and 78%, respectively.
• Overall, they estimated that about 20% of the association between Life's Essential 8 score and cardiovascular disease outcomes was due to the effect of cardiovascular health factors on DNA methylation. In contrast, for participants at high genetic risk, the association was almost 40%.

“There are some commercially available biological age calculators based on DNA methylation, but there are no good recommendations on whether people need to know their epigenetic age,” Ma said. “Our message is that everyone should be mindful of the eight health factors for heart disease and stroke: eat healthy foods, be more active, quit smoking, get healthy sleep, manage your weight, and maintain healthy cholesterol, blood sugar, and blood pressure.”

Randy Foraker, PhD, MA, FAHA, co-author of “Life's Essential 8: Updating and Enhancing the American Heart Association's Construct of Cardiovascular Health,” said the findings are consistent with previous research.

“We know that modifiable risk factors and DNA methylation are each independently associated with cardiovascular disease. What this study adds is that DNA methylation may act as a mediator between risk factors and cardiovascular disease,” said Foraker, professor of medicine in the Institute of Informatics, Data Science and Biostatistics and director of the Center for Population Health Informatics at Washington University School of Medicine in St. Louis, Mo. “This study sheds light on how cardiovascular health influences biological aging, which has important implications for healthy aging and the prevention of cardiovascular disease and potentially other health conditions.”

Study details, background and design:

• The study analyzed health data from a subgroup of participants in the Framingham Heart Study who were screened between 2005 and 2008, as well as a third-generation group from 2008 to 2011.
• Participants were followed for an average of 14 years for the first participant's children and 11 years for grandchildren.
• Health outcomes in the analysis included incident cardiovascular disease (coronary heart disease, heart attack, stroke, heart failure), death from any cardiovascular disease, or death from any cause.
• Results were adjusted for sex, age, and alcohol intake. All-cause mortality outcomes were adjusted for the presence of cancer (excluding nonmelanoma skin cancer) or heart disease at study enrollment. Participants who had already been diagnosed with heart disease at study enrollment were excluded from the analysis of new-onset cardiovascular disease.
• The four tools measuring DNA methylation-based epigenetic age scores are based on established algorithms: DunedinPACE Score, PhenoAge, DNAmTL, and GrimAge. The fifth tool, GrimAge PGS, assessed genetic propensity for accelerated biological aging.

Because this study is an analysis of previously collected health data, it cannot prove a causal relationship between cardiovascular health risk factors and DNA methylation. Additionally, DNA methylation measurements were taken from a single time point, limiting the validity of mediation effects. The findings of this study are also limited because participants were primarily of European descent, and the interactions between Life's Essential 8 and genetic aging found in this study may not be generalizable to people of other races and ethnicities.

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

According to the American Heart Association's 2024 Heart Disease and Stroke Statistics, in 2021, heart disease and stroke killed more people in the United States than all types of cancer and chronic lower respiratory tract diseases combined, and caused approximately 19.91 million deaths worldwide.