Social Disadvantage and Fetal Programming of Newborn-Infant Telomere Biology

新生儿端粒生物学的社会劣势和胎儿编程

基本信息

批准号：
9105960
负责人：
ELIZABETH H BLACKBURN
金额：
$ 67.24万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9105960
关键词：
Accounting Address Alcohol or Other Drugs use Animals Attenuated Back Behavioral Biological Biological Markers Biological Process Biology Birth Birth Weight Cellular biology Characteristics Child Child Development Classification Cohort Studies Conceptions Data Development Diet Disadvantaged Discipline of obstetrics Discrimination Disease Early Intervention Early identification Endocrine Equation Ethnic Origin Ethnic group Exposure to Food Functional disorder Future Generations Genomics Genotype Gestational Age Goals Graph Growth Health Hematopoietic Human Hydrocortisone Immune Infant Infection Interleukin-6 Interpersonal Violence Intervention Isoprostanes Length Leukocytes Life Longevity Maintenance Maternal Age Maternal and Child Health Measures Mediating Mediation Minority Mitogens Modeling Mothers National Institute on Aging Newborn Infant Not Hispanic or Latino Oxidative Stress Paternal Age Pathway Analysis Pathway interactions Peripheral Blood Mononuclear Cell Phenotype Physical activity Play Population Pregnancy Process Protocols documentation Proxy Public Health Publishing Race Research Risk Role Skin Sleep Social support Societies Socioeconomic Status Staging Stress Subgroup System Systems Biology Telomerase Testing Time Translational Research Trees Validation Variant Vertical Disease Transmission Vulnerable Populations age related base biophysical properties burden of illness disadvantaged population disorder risk ethnic difference ethnic minority population feeding fetal fetal programming gestational weight gain health difference health disparity intergenerational man maternal stress novel offspring pediatric trauma population health postnatal prenatal stress primary outcome programs prospective psychologic public health relevance racial and ethnic racism sex social socioeconomic disadvantage study population telomere transmission process

项目摘要

DESCRIPTION (provided by applicant): Population health disparities are evident from the earliest stages of the life, persist over the life span, and are perpetuated across generations. Their most salient determinant is exposure to social disadvantage. Research has elucidated how social disadvantage gets biologically embedded to impact disease risk over the life span, but little is known about how its effects are transmitted across generations. Our application addresses this important gap. We propose to investigate the process of intergenerational (mother-to-child) transmission of social disadvantage, with a focus on newborn and infant telomere biology as the primary outcome, the intrauterine period as the transmission time window, and maternal-placental-fetal (MPF) stress biology as the proximate transmission pathway. Telomere dynamics play a fundamental, causal role in the maintenance of genomic and cellular integrity, and telomere dysfunction represents perhaps the most salient antecedent cellular phenotype of disease risk for common, age-related disorders. Animal and human studies converge to support the critical importance of the initial (early life) setting of telomere length (TL) and telomerase activity (TA) for future health and disease risk, but little is currentl known about the determinants of this initial setting. Published and preliminary data by us and others provides biological plausibility for the novel concept that the initial setting of the telomre system is plastic and substantially influenced by developmental conditions. We hypothesize that, at the cellular level, the origins of health disparities may trace back, in part, to the effets of maternal social disadvantage on the on the initial setting of her child's telomere length and telomerase expression capacity, mediated by the "programming" actions of maternal-placental-fetal (MPF) endocrine, immune and oxidative stress biology. We propose to test this hypothesis in a prospective, longitudinal cohort study of N=1,000 child-mother dyads with serial measures across gestation and birth through the first year of life. Because race/ethnicity and socioeconomic status (SES) represent the principal proxy measures of social disadvantage, and because racial/ethnic differences in health are most pronounced between Non-Hispanic Blacks (hereinafter `Black') and Non-Hispanic Whites (hereinafter `White'), our proposed study population will include approximately equal numbers of Black and White mothers and their offspring. A unique strength of this population is the substantial variation in SES not only across but also within the two racial/ethnic groups, which will enable us to extricate their independent and combined (interaction) effects. We also will evaluate whether effects vary by the sex of the child. Specific Aims: A1: To test the hypothesis that maternal social disadvantage is prospectively associated with newborn and infant telomere biology. A2: To test the hypothesis that maternal-placental-fetal (MPF) stress biology mediates the effects of social disadvantage on newborn and infant telomere biology. A3: Identify and quantify the maternal psychological, behavioral and biophysical characteristics that are associated with social disadvantage and may account for its impact on newborn and infant telomere biology. The significance and impact of this study derives from the importance of better understanding the determinants and mechanisms underlying age-related disease risk in minority, disadvantaged populations (NIA Reversibility Initiative 2012) to inform translational research on early identification and intervention.

描述（由申请人提供）：人口健康差异从生命的最初阶段就很明显，在整个生命周期中持续存在，并且在几代人之间持续存在。研究已经阐明了社会劣势是如何从生物学角度产生的。影响整个生命周期的疾病风险，但对其影响如何跨代传播却知之甚少，我们建议研究社会代际（母婴）传播的过程。缺点，重点关注新生儿和婴儿端粒生物学作为主要结果，子宫内时期作为传播时间窗口，母体-胎盘-胎儿（MPF）应激生物学作为最近的传播途径，发挥着基本的因果作用。在维持基因组和细胞完整性方面，端粒功能障碍可能代表了常见的、与年龄相关的疾病风险的最显着的先行细胞表型。动物和人类研究共同支持了最初的至关重要性。（早期生活）端粒的设置长度（TL）和端粒酶活性（TA）对未来健康和疾病风险的影响，但目前对这种初始设置的决定因素知之甚少，我们和其他人发布的初步数据为初始设置的新概念提供了生物学合理性。端粒系统是可塑的，并且在很大程度上受到发育条件的影响，我们相信，在细胞水平上，健康差异的根源可能部分归因于母亲的社会劣势对其初始环境的影响。儿童的端粒长度和端粒酶表达能力是由母体-胎盘-胎儿 (MPF) 内分泌、免疫和氧化应激生物学的“编程”作用介导的。我们建议在一项对 1,000 名儿童进行的前瞻性纵向队列研究中检验这一假设。 - 母亲二元组，在怀孕和出生到生命第一年期间进行一系列测量，因为种族/民族和社会经济地位（SES）代表了社会劣势的主要代理措施，并且由于健康方面的种族/民族差异在非西班牙裔黑人（以下简称“黑人”）和非西班牙裔白人（以下简称“白人”）之间最为明显，因此我们提议的研究人群将包括数量大致相等的黑人和白人母亲及其后代该群体的一个独特优势是社会经济地位的巨大差异不仅存在于不同国家之间。而且在两个种族/族裔群体中，这将使我们能够摆脱其独立和组合（相互作用）的影响。我们还将评估影响是否因孩子的性别而异：A1：检验母亲的假设。社会劣势与新生儿和婴儿端粒生物学存在前瞻性关联 A2：检验母体-胎盘-胎儿（MPF）应激生物学介导社会劣势对新生儿和婴儿端粒生物学的影响的假设。量化与社会劣势相关的母亲心理、行为和生物物理特征，并可能解释其对新生儿和婴儿端粒生物学的影响。这项研究的意义和影响源于更好地理解与年龄相关的决定因素和机制的重要性。少数民族、弱势群体的疾病风险（NIA 可逆性倡议 2012），为早期识别和干预的转化研究提供信息。