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Background <p>The effects of obesity and reduced thyroid function vary with age. However, studies integrating obesity, thyroid hormone signaling, and aging are limited. This study aimed to explore age-related discrepancies involving obesity and alterations in thyroid hormone signaling.</p> Methods <p>Data on obesity, thyroid hormone signaling, and phenotypic age were collected from 4425 U.S. adults (51.54% male, mean age: 46.44 ± 0.61&#xa0;years) participating in the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression, restricted cubic spline (RCS), and mediation analysis were used to identify risk factors associated with phenotypic age acceleration (PhenoAgeAccel). Additionally, stratified analyses by age were conducted to examine age-related differences.</p> Results <p>In the overall population, body mass index (BMI) and visceral adiposity index (VAI) positively correlated with PhenoAgeAccel. The multivariable-adjusted ORs of the highest quartile of BMI and VAI were 4.89 (3.60–6.64) and 2.96 (2.24–3.91). VAI partially mediated the association between BMI and PhenoAgeAccel (16.67% and 32.19% mediation for continuous variables and quartiles, respectively; <i>p &lt;</i> 0.001). However, after age stratification, VAI was no longer correlated with age acceleration in older adults. Moreover, free triiodothyronine to free thyroxine ratio (FT3/FT4) became an independently protective factor against aging acceleration in the elderly. The OR (95% Cl) for the highest FT3/FT4 quartile was 0.30 (0.18–0.48). A masking effect of FT3/FT4 was also observed on the relationship between VAI and PhenoAgeAccel (30.16% mediation; <i>p &lt;</i> 0.001).</p> Conclusion <p>Obesity appears to accelerate phenotypic age partly through the accumulation of visceral fat in an age-dependent manner. The FT3/FT4 ratio may exert protective effects against phenotypic age acceleration and may partially mask the association between VAI and phenotypic age acceleration in elderly adults.</p> Key points <p>• <i>Obesity accelerates phenotypic age, partially due to visceral fat accumulation.</i></p> <p>• <i>FT3/FT4 protects against phenotypic age acceleration only in elderly adults.</i></p> <p>• <i>The age-related discrepancy of VAI in accelerating phenotypic age is related to the masking effect of FT3/FT4.</i></p>

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Deciphering the obesity paradox in phenotypic age acceleration through thyroid hormone sensitivity: results from NHANES 2007–2010

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Yiming Wang,
  • Hao Zhu,
  • Chenwen Yuan,
  • Jing Liu,
  • Xiaodong Wang,
  • Yu Duan

摘要

Background

The effects of obesity and reduced thyroid function vary with age. However, studies integrating obesity, thyroid hormone signaling, and aging are limited. This study aimed to explore age-related discrepancies involving obesity and alterations in thyroid hormone signaling.

Methods

Data on obesity, thyroid hormone signaling, and phenotypic age were collected from 4425 U.S. adults (51.54% male, mean age: 46.44 ± 0.61 years) participating in the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression, restricted cubic spline (RCS), and mediation analysis were used to identify risk factors associated with phenotypic age acceleration (PhenoAgeAccel). Additionally, stratified analyses by age were conducted to examine age-related differences.

Results

In the overall population, body mass index (BMI) and visceral adiposity index (VAI) positively correlated with PhenoAgeAccel. The multivariable-adjusted ORs of the highest quartile of BMI and VAI were 4.89 (3.60–6.64) and 2.96 (2.24–3.91). VAI partially mediated the association between BMI and PhenoAgeAccel (16.67% and 32.19% mediation for continuous variables and quartiles, respectively; p < 0.001). However, after age stratification, VAI was no longer correlated with age acceleration in older adults. Moreover, free triiodothyronine to free thyroxine ratio (FT3/FT4) became an independently protective factor against aging acceleration in the elderly. The OR (95% Cl) for the highest FT3/FT4 quartile was 0.30 (0.18–0.48). A masking effect of FT3/FT4 was also observed on the relationship between VAI and PhenoAgeAccel (30.16% mediation; p < 0.001).

Conclusion

Obesity appears to accelerate phenotypic age partly through the accumulation of visceral fat in an age-dependent manner. The FT3/FT4 ratio may exert protective effects against phenotypic age acceleration and may partially mask the association between VAI and phenotypic age acceleration in elderly adults.

Key points

• Obesity accelerates phenotypic age, partially due to visceral fat accumulation.

• FT3/FT4 protects against phenotypic age acceleration only in elderly adults.

• The age-related discrepancy of VAI in accelerating phenotypic age is related to the masking effect of FT3/FT4.