Increased Depression, Anxiety, and Stress Survey (DASS) scores are associated with increased epigenetic age acceleration in a prospective study
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Background. Epigenetic age acceleration (EAA), a measure of biological ageing based on DNA methylation, is known to be affected by environmental and social factors, and to be predictive of systemic morbidity and mortality. This epidemiologic study assessed temporal changes in EAA in relation to temporal changes in perceived stress, anxiety, and depression.
Methods. DNA methylation was measured in 279 blood samples (3 per person at 4-month intervals) from 97 adults (mean age 58 years, range 31–85 years) using Illumina EPIC microarrays. Epigenetic age values were estimated using formulas developed by Hannum et al. (2013) and Li et al. (2018), and EAA values were calculated as residuals from regressing them on chronological age. Two EAA slopes for each person were derived from linear regression of EAA values on time. Depression, Anxiety, and Stress Survey (DASS) questionnaires were administered at baseline and end of follow-up. Results were scored for each component using the standard DASS methodology.
Results. Temporal changes in depression, anxiety, and stress scores were consistently positively but not statistically significantly associated with both Li’s and Hannum’s EAA slopes in linear regression models. Stronger evidence of associations was observed when combining Li’s and Hannum’s EAA slopes into a single ordinal outcome variable with three categories: (1) both slopes negative (N=19); (2) slopes in different directions (N=43); and (3) both slopes positive (N=35). Ordinal logistic models with non-proportional odds adjusted for baseline EAA values showed that ten-point increases in depression, anxiety, stress, and total DASS scores were associated with 4.4 (95% confidence limits 1.3; 15), 2.1 (0.7; 6.6), 2.8 (1.1; 7.3), and 1.9 (1.2; 3.2) odds ratios of having two positive slopes vs. two negative slopes.
Conclusion. This study linked, for the first time, temporal increases in stress, anxiety, and depression levels with epigenetic aging.