Telomere Length in Epidemiology: A Biomarker of Aging, Age-Related Disease, Both, or Neither?
Telomere Length in Epidemiology: A Biomarker of Aging, Age-Related Disease, Both, or Neither?
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DOI：
10.1093/epirev/mxs008
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发表时间：
2013-02-04
影响因子：
5.5
通讯作者：
Newman, Anne B.
中科院分区：
文献类型：
--
作者：
Sanders, Jason L.;Newman, Anne B.
端粒是DNA两侧的核蛋白帽。它们因细胞分裂和氧化应激而缩短，并因端粒酶和有丝分裂期间的DNA交换而延长。短端粒诱导细胞衰老。作为氧化应激和衰老（两个过程被认为是衰老的基础）的指标，端粒长度被假设为衰老的生物标志物。这个假设已经用流行病学研究方法验证了十多年。在横断面研究中，研究人员调查了白细胞端粒长度（LTL）是否与人口统计学、行为和健康变量相关。在前瞻性研究中，基线LTL被用于预测死亡率和偶尔的其他不良健康结果。相互矛盾的数据引发了关于LTL作为整体衰老生物标志物的价值的激烈争论。在这篇综述中，我们分析了LTL的流行病学数据，并证明较短的LTL与年龄、男性、高加索人种以及可能的动脉粥样硬化有关；与其他健康指标的关联并不明确。我们讨论了研究差异的原因，包括对端粒长度测量方法的详细回顾，因为它们适用于流行病学。最后，我们总结了LTL作为衰老生物标志物的问题，以及如何使用流行病学来回答这些问题。
Telomeres are nucleoprotein caps flanking DNA. They are shortened by cell division and oxidative stress and are lengthened by the enzyme telomerase and DNA exchange during mitosis. Short telomeres induce cellular senescence. As an indicator of oxidative stress and senescence (2 processes thought to be fundamental to aging), telomere length is hypothesized to be a biomarker of aging. This hypothesis has been tested for more than a decade with epidemiologic study methods. In cross-sectional studies, researchers have investigated whether leukocyte telomere length (LTL) is associated with demographic, behavioral, and health variables. In prospective studies, baseline LTL has been used to predict mortality and occasionally other adverse health outcomes. Conflicting data have generated heated debate about the value of LTL as a biomarker of overall aging. In this review, we address the epidemiologic data on LTL and demonstrate that shorter LTL is associated with older age, male gender, Caucasian race, and possibly atherosclerosis; associations with other markers of health are equivocal. We discuss the reasons for discrepancy across studies, including a detailed review of methods for measuring telomere length as they apply to epidemiology. Finally, we conclude with questions about LTL as a biomarker of aging and how epidemiology can be used to answer these questions.