Longitudinal Associations Between Medication Use and Phenotypic Aging: Insights from the Baltimore Longitudinal Study of Aging.

Background: Limited population-based data exist on the association between medication use and changes in phenotypic aging. This study investigated these associations using data from the Baltimore Longitudinal Study of Aging.

Methods: Phenotypic aging (PA) markers were constructed using the Klemera-Doubal (KD) method across four domains: body composition (structural and metabolic changes), energetics (energy generation and utilization capacity), homeostatic mechanisms (internal stability maintenance), and neuroplasticity/neurodegeneration (nervous system function and decline). Associations between 27 common drug categories and changes in these PA markers were analyzed using conditional generalized estimating equations (cGEE), focusing on within-individual variation to control for genetics and early-life factors, with additional adjustments for time-varying covariates.

Results: Five drug categories were associated with significant reductions in PA markers. Vitamin D, bisphosphonates, and proton pump inhibitors were linked to decreases in body composition (Beta = -0.73 years, 95% CI: -1.35 to - 0.10), energetics (Beta = -2.05, 95% CI: -3.98 to - 0.13), and neuroplasticity/neurodegeneration (Beta = -1.00, 95% CI: -2.02 to - 0.03), respectively. Thyroid hormones showed reductions in body composition (Beta = -1.75, 95% CI: -3.24 to - 0.26) and neuroplasticity/neurodegeneration (Beta = -1.04, 95% CI: -1.96 to - 0.12). Thiazides were associated with decreases across body composition (Beta = -1.55, 95% CI: -2.94 to - 0.16), energetics (Beta = -2.36, 95% CI: -4.30 to - 0.42), and homeostatic mechanisms (Beta = -3.83, 95% CI: -6.71 to - 0.96).

Conclusions: These findings suggest potential protective effects of certain medications on phenotypic aging. Further research is needed to validate these results, particularly with data from other populations.