Social status, cellular aging, and mortality

描述(由申请人提供)：大量证据表明，低社会经济地位(SES)与年龄相关疾病的发展和早期死亡率有关。其生物学机制尚未得到很好的阐明，尽管这似乎部分是由于长期暴露在应激条件下和应激介导的损害。端粒(染色体末端的DNA帽)的维持可能与疾病过程和过早死亡有关。白细胞端粒长度通常随着年龄和慢性应激而缩短，并独立于年龄而预测死亡率。此外，最近的一项研究发现，社会经济地位较低的人端粒较短。因此，白细胞端粒长度可能会将社会劣势与早期死亡率联系起来，这也是本研究的重点。方法：利用1999-2002年国家健康和营养检查调查(NHANES)的数据，这项拟议的研究将首次在具有全国代表性的样本中检查端粒长度，使我们能够扩展过去的发现，将SES与较短的端粒长度联系起来，并将端粒长度与死亡率联系起来。我们将能够在不同种族和民族的样本中检查这些关系，并检查遗传脆弱性的调节作用，以及健康行为和心理健康的中介作用。我们的跨学科团队代表流行病学、遗传学、生物统计学、心理学和社会学。我们将从存档的DNA中测量端粒长度和三个调节端粒长度的基因(TERT、TERC、PINX1)的多态，这些基因来自大约7,200名年龄在20岁到85岁以上的男性和女性，他们参与了NHANES 1999-2002年的研究。我们将研究SES是否预测端粒长度，以及这是否通过健康行为和心理健康来调节。我们还将研究基因与环境的相互作用，特别是低SES是否与这三个基因的多态相互作用来预测端粒长度。最后，在50岁以上的样本中，我们将检验端粒长度是否预测8年后的死亡率，以及端粒长度是否中介了SES和死亡率之间业已确立的关系。对于所有分析，我们将检查整个样本和三个种族/民族群体(即墨西哥裔美国人、非裔美国人和非西班牙裔白人)之间是否存在关系。相关性：这项研究将有助于确定社会劣势是否与端粒缩短有关；SES和端粒长度之间关系的行为和心理健康调节因素和遗传调节因素；以及端粒长度是否调节SES低和早期死亡率之间的关系。因此，它将有助于确定端粒长度是否可能成为监测和干预目标的有用风险因素。了解衰老过程对于预防过早发病和死亡以及延长健康寿命至关重要。 公共卫生相关性：这项研究将提供可能的干预措施和政策，以帮助国家实现消除健康差距的2010年健康人目标，这需要了解差距形成的机制。这项拟议研究的结果将阐明细胞衰老是一种生物途径，通过这种途径，社会劣势可能会增加过早死亡的脆弱性。利用具有全国代表性的样本，它将提供关于种族/民族群体内和跨种族/民族群体的社会经济地位的作用以及与遗传脆弱性的相互作用在确定细胞老化方面的数据，进而提供细胞老化如何预测死亡率的数据。

DESCRIPTION (provided by applicant): A large body of evidence links low socioeconomic status (SES) to the development of age- related diseases and to earlier mortality. The biological mechanisms are not well elucidated, although it appears to be in part through chronic exposure to stressful conditions and stress-mediated damage. The maintenance of telomeres (the DNA caps at the ends of chromosomes) may be mechanistically involved in disease processes and premature mortality. Leukocyte telomere length generally shortens with chronological age and with chronic stress, and predicts mortality independent of age. Further, a recent study found shorter telomeres in people with low socioeconomic status (SES). Leukocyte telomere length thus may link social disadvantage to earlier mortality, and is the focus of this study. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 1999- 2002, the proposed study will be the first to examine telomere length in a nationally representative sample, allowing us to expand on past findings linking SES to shorter telomere length, and telomere length to mortality. We will be able to examine these relationships in a racially and ethnically diverse sample, and examine moderating effects of genetic vulnerabilities, as well as mediating effects of health behaviors and mental health. Our interdisciplinary team represents epidemiology, genetics, biostatistics, psychology, and sociology. We will measure telomere length and polymorphisms in three genes (TERT, TERC, PINX1) that regulate telomere length from archived DNA in approximately 7,200 men and women, aged 20 to 85+, who participated in the NHANES 1999-2002 study. We will examine whether SES predicts telomere length and whether this is mediated by health behaviors and mental health. We will also examine gene-environment interactions, specifically whether low SES interacts with polymorphisms in these 3 genes to predict telomere length. Lastly, in the sample over 50 years of age, we will examine whether telomere length predicts mortality 8 years later, and whether telomere length mediates the well-established relationship between SES and mortality. For all analyses, we will examine whether relationships exist across the entire sample and within three racial/ethnic groups (i.e., Mexican-Americans, African-Americans, and non-Hispanic Whites). Relevance: This study will help determine if social disadvantage is linked to telomere shortening; the behavioral and mental health mediators and genetic moderators of the association between SES and telomere length; and if telomere length mediates the relationship between low SES and early mortality. It will thus help determine whether telomere length might become a useful risk factor to monitor and target of intervention. Understanding the aging process is central to preventing premature morbidity and mortality and to lengthening the healthy lifespan. PUBLIC HEALTH RELEVANCE: This study will inform possible interventions and policies to help the nation to achieve the Healthy People 2010 goal of eliminating health disparities, which necessitates understanding the mechanisms by which disparities develop. Findings from the proposed research will shed light on cellular aging as a biological pathway through which social disadvantage may increase vulnerability to premature mortality. Using a nationally representative sample, it will provide data on the role of socioeconomic status within and across racial/ethnic groups and the interaction with genetic vulnerabilities in determining cell aging, and in turn, how cell aging predicts mortality.