Zhu Yue, Gao Yufan, Lu Yangguang, Wang Yukai, Pan Ziyu, Sheng Huixiang, Li Jiajun, Chen Yinuo, Lou Jialing, Chen Feng, Yang Fajing
The School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
Tob Induc Dis. 2025 May 8;23. doi: 10.18332/tid/203865. eCollection 2025.
Aging is an irreversible biological process significantly influenced by oxidative stress, which smoking exacerbates. While the impact of direct smoking on aging is well-documented, the association between secondhand smoke (SHS) exposure and biological aging remains less explored. This study examines the connection between SHS exposure in populations and biological aging, highlighting diabetes as a potential mediator due to its established links to both SHS exposure and accelerated aging through mechanisms such as oxidative stress and chronic inflammation. It further employs genetic tools to establish a causal relationship between SHS exposure and biological aging.
This study combines secondary dataset analyses and Mendelian randomization analyses. Data from the NHANES 1999-2010 cycles were used, with serum cotinine levels indicating SHS exposure and phenotypic age, derived from age and clinical biomarkers reflecting inflammation, metabolism, and hematologic function, as the measure of biological aging. Multifactorial linear regression assessed associations, with restricted cubic splines used to explore nonlinear trends. Subgroup and mediation analyses were conducted to explore population-specific effects and the mediating role of diabetes. Two-sample Mendelian randomization (MR) using GWAS summary statistics on workplace SHS exposure (N=90168) and phenotypic age acceleration (N=6148) assessed causality.
In the NHANES analysis, low SHS exposure was associated with a 0.37-year increase in biological aging (β=0.37; 95% CI: 0.04-0.70), while high exposure showed a 0.76-year increase (β=0.76; 95% CI: 0.23-1.29). A U-shaped association was found between log-transformed serum cotinine and biological aging (p<0.001), with a threshold at -1.53. Diabetes mediated 31.25% of this association. In the MR analysis, workplace SHS exposure was causally linked to a 3.05-year acceleration in aging (β=3.05; 95% CI: 0.24-5.85).
SHS exposure accelerates biological aging, partly via diabetes. Genetic evidence supports a causal effect, emphasizing the need to minimize SHS exposure.
衰老是一个不可逆转的生物学过程，受到氧化应激的显著影响，而吸烟会加剧这种影响。虽然直接吸烟对衰老的影响已有充分记录，但二手烟暴露与生物衰老之间的关联仍有待深入研究。本研究探讨了人群中二手烟暴露与生物衰老之间的联系，强调糖尿病作为潜在中介因素，因为它通过氧化应激和慢性炎症等机制与二手烟暴露和加速衰老都存在既定联系。本研究还运用遗传工具来确定二手烟暴露与生物衰老之间的因果关系。
本研究结合了二次数据集分析和孟德尔随机化分析。使用了1999 - 2010年美国国家健康与营养检查调查（NHANES）周期的数据，血清可替宁水平表明二手烟暴露情况，而表型年龄由年龄以及反映炎症、代谢和血液学功能的临床生物标志物得出，作为生物衰老的衡量指标。多因素线性回归评估关联，使用受限立方样条来探索非线性趋势。进行亚组分析和中介分析以探讨特定人群效应和糖尿病的中介作用。使用关于工作场所二手烟暴露（N = 90168）和表型年龄加速（N = 6148）的全基因组关联研究（GWAS）汇总统计数据进行两样本孟德尔随机化（MR）分析来评估因果关系。
在NHANES分析中，低二手烟暴露与生物衰老增加0.37年相关（β = 0.37；95%置信区间：0.04 - 0.70），而高暴露则显示增加0.76年（β = 0.76；95%置信区间：0.23 - 1.29）。在对数转换后的血清可替宁与生物衰老之间发现了U形关联（p < 0.001），阈值为 - 1.53。糖尿病介导了这种关联的31.25%。在MR分析中，工作场所二手烟暴露与衰老加速3.05年存在因果关系（β = 3.05；95%置信区间：0.24 - 5.85）。
二手烟暴露会加速生物衰老，部分是通过糖尿病。遗传证据支持因果效应，强调需要尽量减少二手烟暴露。
