DunedinPACE showed consistent associations of accelerated epigenetic aging with multiple cardiometabolic conditions, and all three epigenetic clocks showed accelerated aging among individuals with diabetes in a Guatemalan adult cohort.
Key Findings
Results
The study population showed accelerated biological aging across all three epigenetic clocks.
Sample consisted of 1,095 Guatemalan adults with mean age 45 years, 60.3% female.
DunedinPACE mean was 1.2 (SD 0.1), indicating a faster pace of aging than the reference population (where 1.0 is expected).
PhenoAge mean was 46.7 years (SD 6.7) and GrimAge mean was 56.3 years (SD 4.1), both suggesting older biological than chronological age.
Pearson correlations among the three clocks were ≥ 0.5.
Results
All three epigenetic clocks showed accelerated aging among individuals with diabetes.
15.4% of participants had diabetes.
DunedinPACE association with diabetes: β = 0.09 (95% CI: 0.07, 0.10).
PhenoAge association with diabetes: β = 2.69 (95% CI: 1.63, 3.74).
GrimAge association with diabetes: β = 1.18 (95% CI: 0.71, 1.65).
Diabetes showed the most consistent associations across all three clocks compared to other cardiometabolic conditions.
Results
DunedinPACE indicated a faster rate of biological aging across all cardiometabolic conditions examined.
Cardiometabolic conditions examined included obesity, hypertension, diabetes, and metabolic syndrome.
73.3% of participants were overweight or obese, 37.8% had hypertension, and 66.9% had metabolic syndrome.
The strength and consistency of associations for PhenoAge and GrimAge varied by condition, unlike DunedinPACE.
DunedinPACE was described as showing the most consistent associations with multiple cardiometabolic conditions across all clocks.
Results
Epigenetic age acceleration showed differential patterns by sex depending on the clock used.
DunedinPACE indicated age acceleration among women: β = 0.04 (95% CI: 0.03, 0.05).
PhenoAge indicated age acceleration among women: β = 0.94 (95% CI: 0.28, 1.60).
GrimAge suggested age acceleration among men: β = -1.02 (95% CI: -1.31, -0.72).
The direction of sex-based epigenetic age acceleration differed across clocks, with GrimAge showing the opposite pattern from DunedinPACE and PhenoAge.
Methods
The study used DNA methylation from buffy coat samples and three distinct epigenetic clocks to measure biological aging in a Guatemalan cohort.
DNA methylation was assessed in buffy coat samples using the MethylationEPIC v2 array with standard quality control procedures.
Epigenetic age was quantified using DunedinPACE, PhenoAge, and GrimAge.
Participants were drawn from the INCAP Nutritional Supplementation Trial Cohort.
Linear regression models assessed associations with cardiometabolic outcomes, with covariates including sex, birth year, and a clustering variable to account for sibships.
Most epigenetic clocks were developed and validated in Western populations, making this Guatemalan cohort an understudied context.
Chapnick M, Yu E, Smith A, Conneely K, Ramírez-Zea M, Qin Z, et al.. (2026). Epigenetic age and cardiometabolic disease in Guatemalan adults: a cross-sectional analysis.. Journal of health, population, and nutrition. https://doi.org/10.1186/s41043-026-01255-4