Life's Simple 7 score and epigenetic age acceleration: associations and effect modification by race and ethnicity

Why it matters

Epigenetic clocks estimate a person's biological age from chemical tags called methyl groups on their DNA. When the clock reads older than a person's real age, that gap is called epigenetic age acceleration, and it has been proposed as one reason heart disease rates differ between racial and ethnic groups. A problem is that most clocks were built using samples from mostly or only White people, so it is not clear they work the same way in everyone. Before these clocks can be used to study health disparities, researchers need to know whether their links with health hold across groups. This study tests that using a widely used measure of heart health.

What they did

The team used data from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, a nationally representative sample. They included 2,401 adults aged 50 to 84 who were non-Hispanic Black, non-Hispanic White, Mexican American, other Hispanic, or another race or ethnicity. They scored each person on the American Heart Association's Life's Simple 7 (LS7), which covers seven factors such as blood pressure, cholesterol and activity. They then compared LS7 with 13 standardised measures of epigenetic age, adjusting for other factors, and tested whether the relationship changed by race and ethnicity.

What they found

People with higher LS7 scores, meaning better cardiovascular health, had lower epigenetic age acceleration on six measures: Hannum, PhenoAge, GrimAge, GrimAge2, DunedinPoAm and a methylation-based telomere measure, where the direction pointed to longer estimated telomeres. The strongest links were for GrimAge (a coefficient of about -0.14) and GrimAge2 (about -0.16). Seven measures, including the original Horvath clock, showed no significant link. Apart from one exception involving the Horvath clock, the relationship did not differ by race and ethnicity. The authors conclude there was not enough evidence of differences between groups, and that clocks trained on physiological age, rather than calendar age, gave the most consistent results and may be useful for disparities research.

Limits

This synopsis is based on the abstract only, although the paper is open access. The study is cross-sectional, measuring everyone at one time, so it shows association, not that better heart health slows epigenetic aging. The data were collected over 20 years ago. Finding no significant difference between groups is not the same as proving the clocks behave identically, since some groups were likely smaller. The coefficients are reported in standardised units, so they do not translate directly into years of age.

Key terms

Epigenetic clock

A formula that estimates age from DNA methylation levels at selected sites in the genome.

Epigenetic age acceleration

How much older (or younger) a person's epigenetic age is than their actual age.

GrimAge / PhenoAge

Second-generation clocks trained to predict health and mortality, not just calendar age.

DunedinPoAm

A methylation measure of the pace of aging, built from changes in body systems over time.

Life's Simple 7

An American Heart Association score of seven heart-health factors, including blood pressure, cholesterol, blood sugar, weight, diet, activity and smoking.

NHANES

A long-running US government survey that combines interviews, physical exams and lab tests.