Age-specific relationships between free triiodothyronine and biological aging.

Objective: Our study aims to examine the associations of thyroid function parameters with phenotypic age acceleration (PhenoAgeAccel) in different age groups.

Method: The analysis included 7,564 participants from the NHANES 1999-2018. PhenoAgeAccel was defined as calculated phenotypic age (PhenoAge) exceeding chronological age. Weighted multivariable logistic regression models were used to analyze the relationship between free triiodothyronine (FT3) and PhenoAgeAccel. The restricted cubic spline method was used to assess nonlinear associations of FT3 level with PhenoAgeAccel. Nomogram and the receiver operating characteristic (ROC) curve were constructed to evaluate the diagnostic performance of the predictive model.

Results: Higher FT3 levels were associated with increased risk of PhenoAgeAccel in participants under 60 years old (OR: 1.316, 95% CI: (1.010, 1.715), p = 0.042). For those aged 60 years and above, higher FT3 levels were linked with decreased risk of PhenoAgeAccel (OR: 0.485, 95% CI: (0.309, 0.761), p = 0.002). These associations were more pronounced in males than in females. Restricted cubic spline curves showed similar trends between FT3 levels and PhenoAgeAccel in both age subgroups. The ROC curves including FT3 indicated that both models had fair prediction performance (age >  = 60 years, AUC = 0.722 (0.700-0.743); age < 60 years, AUC = 0.765 (0.751- 0.780)).

Conclusion: This study revealed a novel age-dependent association between FT3 levels and biological aging acceleration, with lower FT3 potentially serving as a biomarker for accelerated aging in elderly individuals, while an inverse relationship was observed in younger adults. The study provides novel insights into the intricate relationship between thyroid function and systemic health across the lifespan.