Aging
Sex-specific associations between thyroid hormones and biological aging Rebecca Stutz* Rebecca Stutz Stutz Stutz Department of Epidemiology and Environmental Health, University at Buffalo
Background: Thyroid hormones are master regulators of the metabolic function, which is a core component of biological aging. DNA methylation-based epigenetic clocks, particularly DunedinPoAm, are promising biomarkers of the rate of biological aging, i.e., how fast one ages biologically. However, the thyroid hormonal regulation of the rate of biological aging in adults remains largely unexplored.
Objective: To investigate the association of thyroid hormones with DunedinPoAm using the representative sample from the National Health and Nutrition Examination Survey (NHANES).
Methods: NHANES, a cross-sectional survey of the U.S. non-institutionalized population, assesses lifestyle, nutrition, and health status. From 1999 to 2002, thyroid hormones, including thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured by immunoassay. Among these participants, 831 also had DunedinPoAm estimates from DNAm. We used linear regression models to examine the independent and interactive associations of T4 and TSH with DunedinPoAm, adjusting for demographics, lifestyle factors, and comorbidity. The analysis was stratified by sex to evaluate sex-specific effects.
Results: In males, T4 appeared to accelerate the rate of aging, with a 1-unit increase in T4 associated with a 0.80% (95% CI: 0.28, 1.33) higher DunedinPoAm age acceleration after adjusting for confounders. There is a small, but significant interaction between T4 and TSH where the beta for the interaction term was 0.04% (95% CI: -0.03, 0.11). In females, T4 and TSH both appeared to decelerate aging (T4: β = -0.8%, 95% CI: -1.4, -0.2, TSH: β = -1.7%, 95% CI: -3.5, 0) in the fully adjusted model. T4 and TSH also showed positive and significant interaction (β = 0.3%, 95% CI: 0.07, 0.5).
Conclusion: Among people older than 50 years, thyroid hormones had sex-specific associations with the rate of biological aging, where T4 can accelerate DunedinPoAm in males, but T4 and TSH can decelerate DunedinPoAm in females.