Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94118, USA.
Brain Res. 2011 Mar 16;1379:224-31. doi: 10.1016/j.brainres.2010.10.033. Epub 2010 Oct 18.
Longer duration of reproductive years of life and thus greater exposure to endogenous estrogen may be associated with a lower risk of age-related diseases in women. The present study examined the relationship between estimated endogenous estrogen exposure and telomere length (TL) and telomerase activity, two biomarkers of cellular aging, in a sample of postmenopausal women at risk for cognitive decline. Telomere length was measured using a quantitative PCR method and telomerase activity by TRAP (Telomere-Repeats Amplification Protocol) assay in peripheral blood mononuclear cells (PBMCs). Study subjects were 53 postmenopausal women (35 with natural and 18 with surgical menopause) receiving hormone therapy (HT) for at least one year or longer. Length of reproductive years of life, computed as the difference between age at menopause and age at menarche, was used as a proxy of duration of exposure to endogenous estrogen. Length of time on HT was the measure used for duration of exogenous estrogen exposure. We found that longer endogenous estrogen exposure was associated with greater TL (standardized β=0.06, Wald χ(2)=3.7, p=0.04) and with lower telomerase activity (standardized β=-0.09, Wald χ(2)=5.0, p=0.03). Length of reproductive years was also inversely associated with the combination of short TL and high telomerase (OR=0.78, 95% CI: 0.63, 0.97, p=0.02). Length of HT use was not associated with TL or telomerase activity in this study. The results suggest that the endogenous estrogens may be associated with deceleration of cellular aging. This is the first study to examine associations between endogenous estrogens, telomere length and telomerase activity.
生育年限较长，即女性有更多的内源性雌激素暴露时间，可能与女性与年龄相关疾病的低风险相关。本研究在有认知能力下降风险的绝经后妇女样本中，检查了内源性雌激素暴露估计值与端粒长度（TL）和端粒酶活性（细胞衰老的两个生物标志物）之间的关系。端粒长度通过定量 PCR 方法测量，端粒酶活性通过 TRAP（端粒重复扩增协议）测定法在外周血单核细胞（PBMCs）中测量。研究对象为 53 名绝经后妇女（35 名自然绝经，18 名手术绝经），她们接受激素治疗（HT）至少一年或更长时间。生育年限的计算方法是绝经年龄与初潮年龄之差，用作内源性雌激素暴露时间的替代指标。HT 的使用时间是用于测量外源性雌激素暴露时间的指标。我们发现，较长的内源性雌激素暴露与较长的 TL 相关（标准化β=0.06，Wald χ²=3.7，p=0.04），与较低的端粒酶活性相关（标准化β=-0.09，Wald χ²=5.0，p=0.03）。生育年限也与 TL 短和端粒酶活性高的组合呈负相关（OR=0.78，95%CI：0.63，0.97，p=0.02）。在本研究中，HT 的使用时间与 TL 或端粒酶活性无关。结果表明，内源性雌激素可能与细胞衰老的减速有关。这是首次研究内源性雌激素、端粒长度和端粒酶活性之间的关联。
