In a recent study published in the journal JAMA Network Open, researchers conducted a cross-sectional study of midlife-aged Black and White women to evaluate the impacts of diets (specifically, consumption of added sugar and essential nutrients) on their epigenetic age. Their study comprised 342 women (171 Black and 171 White) whose 3-day dietary intakes were scored using the Alternate Health Eating Index (AHEI), the Alternate Mediterranean Diet (aMED), and a novel Epigenetic Nutrient Index (ENI).
Study: Essential Nutrients, Added Sugar Intake, and Epigenetic Age in Midlife Black and White Women. Image Credit: Kateryna Kon / Shutterstock
Study findings revealed that healthy diets with high aMED, AHEI, and ENI scores were associated with younger epigenetic ages (measured using the second-generation GrimAge2 epigenetic clock marker). Added sugar intakes were found to have the opposite effect, with high intakes corresponding to increased epigenetic age. The results quantified that each unit increase in aMED score was associated with a reduction in epigenetic age (β, -0.41), AHEI-2010 (β, -0.05), and ENI (β, -0.17), while each gram increase in added sugar intake was associated with an increase in epigenetic age (β, 0.02). Together, these findings suggest the profound impacts of dietary behaviors on epigenetic aging and, in turn, risk susceptibility to chronic disease.
Background
Epigenetic clocks are biochemical tests that measure an individual’s biological aging independent of chronological age. They are based on differential DNA methylation (DNAm) and have been shown to accurately predict an individual’s susceptibility to chronic, age-associated disease risk (e.g., cancers, cardiovascular disease).
Several epigenetic clock markers have been developed due to their use in evaluating the toll of behavioral, social, and environmental variables on holistic health and disease risk. The first-generation GrimAge marker is one of the most popular due to its sensitivity to the associations between genomic instability, oxidative stress, and systemic inflammation markers and subsequent mortality and morbidity risk. The GrimAge series has recently been updated to version 2.0 (GrimAge2) with additional predictors and improved applicability across a wide range of ages and ethnicities.
Unfortunately, studies investigating the associations between health behaviors (e.g., diet – ‘epigenetic diet’ and ‘nutriepigenetics’) and epigenetic clock markers are rare. Even in the handful of studies conducted, most focus on White populations, limiting their global generalization potential. Furthermore, while the positive impacts of essential nutrients have been repeatedly verified, sugars (known to increase oxidative stress and suggested to accelerate epigenetic aging) have been notably excluded from the literature.
About the study
The present study aims to address current gaps in the literature by evaluating the epigenetic age associations between established dietary scores (the Alternate Health Eating Index [AHEI], the Alternate Mediterranean Diet [aMED]), a novel Epigenetic Nutrient Index [ENI]), and the GrimAge2 epigenetic clock marker.
It follows a cross-sectional methodology with its study cohort derived from the United States (US) National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) across both original (1987-1999) and follow-up (2015-2019) periods. The cohort comprised Californian White and Black women aged 9-10 at baseline and 36-43 at follow-up. Data collection comprised participant-produced demographic (including race and ethnicity) and health records (including smoking status, chronic disease status, and current medication), salivary samples (for DNAm evaluations), and online surveys (for 3-day dietary assessment).
Epigenetic clock estimations were computed using Horvath’s online calculator based on the GrimAge2 model (outcomes presented as Cox Proportional Hazards regression scores), elucidating all-cause mortality risk. Diet quality indices comprised two established (aMED and AHEI-2010) and one novel (ENI) scoring methodologies, reflecting participants’ adherence to preestablished health eating behaviors. High scores indicate a high intake of anti-oxidant-rich, inflammation-suppressive foods such as fresh fruits and vegetables and low intakes of red meats and ultra-processed foods.
“This study developed a novel nutrient index (ENI) after the Mediterranean-style diet, but via a nutrient-based approach rather than a food-based one. Nutrient selection was done a priori based on antioxidant and/or anti-inflammatory capacities as well as roles in DNA maintenance and repair documented in the literature.”
Added sugar intake was measured, and its impact on GrimAge2 scores was independently analyzed. All models were adjusted for potentially confounding covariates (age, memory and effector T-cell densities, smoking status, chronic disease, and current medication).
Study findings
The final sample cohort (after excluding five individuals with low-quality DNAm data or incomplete records) comprised 342 midlife women (171 Black and White women, respectively). The mean age of the cohort was 39.2 years, with 43.9% (n = 150) smokers, 48.0% chronic disease (n = 164), and 17.0% (n = 58) currently on medication.
Mean scores across dietary indices were AHEI-2010 = 55.4 (Range = 0-9; SD = 14.7), aMED 3.9 (0-110; 1.9), and ENI = 13.5 (-024; 5.0), indicating low to moderate diet quality. Mean sugar intake was 61.5g (SD = 44.6g).
GrimAge2 computations revealed that healthier diets (higher scores) were associated with reduced epigenetic ages per unit score– aMED (β, −0.41), AHEI-2010 (β, −0.05), and ENI β, −0.05). In contrast, every gram increase in daily sugar intake was associated with accelerated aging (β, 0.02).
Conclusions
The present study was the first to assess the association between epigenetic age and dietary intake in non-White women (Black, n = 171), the first to utilize the GrimAge2 clock, and the first to evaluate the role of sugar in epigenetic aging. Furthermore, it introduces a novel dietary evaluation, the ENI index.
Study findings highlight that healthier diets (high aMED, AHEI, or ENI scores) were associated with decreased epigenetic aging, while high sugar intake accelerated DNA methylation. Together, these findings highlight the profound impacts of dietary choices on DNAm and, in turn, the risk of chronic diseases.
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