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有关。其生物学机制尚未得到很好的阐明，尽管它似乎部分是通过长期暴露于应激条件和应激介导的损伤。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年龄和慢性应激而缩短，并预测与年龄无关的死亡率。此外，最近的一项研究发现，社会经济地位低的人的端粒更短。因此，白细胞端粒长度可能将社会劣势与早期死亡联系起来，这是本研究的重点。方法：利用1999- 2002年国家健康与营养调查（NHANES）的数据，该研究将是第一个在全国代表性样本中检查端粒长度的研究，使我们能够扩展过去的研究结果，将SES与端粒长度缩短以及端粒长度与死亡率联系起来。我们将能够在一个种族和民族多样化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。我们的跨学科团队包括流行病学、遗传学、生物统计学、心理学和社会学。我们将测量端粒长度和三个基因（TERT， TERC, PINX1）的多态性，这些基因调节端粒长度，来自大约7200名男性和女性的DNA，年龄在20至85岁以上，他们参加了NHANES 1999-2002年的研究。我们将研究SES是否预测端粒长度，以及这是否由健康行为和心理健康介导。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3个基因的多态性相互作用以预测端粒长度。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，以及端粒长度是否介导了SES与死亡率之间的既定关系。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，非洲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；社会地位与端粒长度关系的行为和心理健康调节因子和遗传调节因子；以及端粒长度是否介导了低社会地位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。

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.