Curtis Sarah W, Cobb Dawayland O, Kilaru Varun, Terrell Metrecia L, Marder M Elizabeth, Barr Dana Boyd, Marsit Carmen J, Marcus Michele, Conneely Karen N, Smith Alicia K
Genetics and Molecular Biology Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Aging (Albany NY). 2019 Aug 2;11(15):5498-5517. doi: 10.18632/aging.102134.
Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
高龄会增加患癌症、心血管疾病和全因死亡率的风险。然而,人们衰老的速度并不相同,生物年龄(通常通过DNA甲基化来衡量)可能比实际年龄更大。环境因素与生物衰老的速度有关,但尚不清楚像多溴联苯(PBB)这样的持久性内分泌干扰化合物(EDC)是否会与年龄加速有关。根据来自高暴露于PBB人群(N = 658)全血中的现有表观遗传数据,计算了三种不同的表观遗传年龄加速指标(内在、外在和表型)。测试了血清PBB浓度与这些指标之间的关联,并控制了性别、血脂水平和估计的细胞类型比例。较高的PBB水平与年龄加速增加有关(内在:β = 0.24,95%CI = 0.01 - 0.46,p = 0.03;外在:β = 0.39,95%CI = 0.12 - 0.65,p = 0.004;表型:β = 0.30,95%CI = 0.05 - 0.54,p = 0.01)。暴露于PBB时的年龄和性别在统计学上均未与PBB相互作用以预测年龄加速,但在分层分析中,PBB与年龄加速之间的关联仅存在于青春期前暴露的人群和男性中。这表明EDC可能与生物衰老过程有关,有必要进一步开展研究以调查其他环境污染物对衰老的影响。