The Developmental Origins of Disease and Deterioration in Old Age

老年疾病和恶化的发育起源

基本信息

批准号：
7886374
负责人：
David J Barker
金额：
$ 17.4万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7886374
关键词：
Accounting Admission activity Adult Affect Age Age at Menarche American Animals Behavior Biochemical Biological Process Birth Birth Records Blood specimen Body Size Body mass index Breast Feeding Cardiovascular Diseases Cardiovascular system Censuses Cessation of life Child Childhood Chronic Disease Cohort Studies Competence Conceptions Coronary heart disease Country DNA Data Data Set Deterioration Development Diabetes Mellitus Diet Disease Economic Conditions Elderly Environment Epigenetic Process Fathers Fatty acid glycerol esters Fetal Malnutrition Fetus Finland Genes Genetic Genotype Growth Head circumference Health Health Benefit Healthcare Height Home environment Hormonal Hospitals Human Human Development Income Individual Infant Infection Investments Length Life Life Expectancy Life Style Link Longevity Longitudinal Studies Low Birth Weight Infant Malignant Neoplasms Malnutrition Measurement Measures Menarche Mental Health Metabolic Metabolism Molecular Mothers Newborn Infant Nutrient Occupations Pathologic Processes Persons Pharmaceutical Preparations Phenotype Physiological Placenta Plastics Pregnancy Prevention strategy Proteins Psyche structure Records Recurrence Relative (related person)Research Risk Sampling Schools Signal Transduction Socioeconomic Status Structure Uterus Variant Weight Woman base cohort critical period developmental plasticity fetus nutrition genome wide association study girls indexing insight men mortality mother nutrition next generation nutrition postnatal programs public health relevance resilience response socioeconomics stressor

项目摘要

DESCRIPTION (provided by applicant): Within any level of socio-economic status there is a wide variation in lifespan. Our hypothesis is that this variation is programmed during development. We propose that poor intrauterine nutrition and poor childhood living conditions initiate pathological processes and permanently change the body's structure and function in ways that make it vulnerable to stressors in postnatal life. Because intrauterine nutrition is determined by the mother's lifetime nutrition our findings will quantify how investment in the nutrition and growth of girls and young women will increase the lifespan of the next generation. The Helsinki Birth Cohort Study of 20,000 people is the only known data set in the world that includes maternal body size, birth size, infant and childhood growth and living conditions of people now at the end of their lives. The cohort includes detailed socioeconomic data recorded at each 5 yearly national census. We also propose that the ability to sustain physical and mental health in old age is programmed during development. We will explore the effects of intrauterine nutrition and childhood living conditions on resilience in old age; and we will examine whether there are periods of growth that are critical for this. This will inform preventive strategies that promote well being in early life and protect vulnerable elderly people. In subsequent studies, which are not the subject of this application, we will use the genome wide scan that has already been carried out to distinguish environmental and genetic effects on resilience in old age. Specific Aim 1: To determine how maternal nutrition and childhood living conditions predict all cause mortality, taking into account socio-economic conditions in later life. In two register-based studies of 7086 and 13,345 men and women, we will relate these early life influences to mortality from all causes and from cardiovascular and non-cardiovascular causes separately. Specific Aim 2: To determine how maternal nutrition and childhood living conditions predict changes in physical and mental health in later life, taking into account adult life-style, socio-economic conditions and illness. In a longitudinal study of a sub-sample of 1600 people we will relate these early life influences to changes in indices of physiological, mental and biochemical health. Specific Aim 3: To determine whether there are critical periods of growth between birth and age eleven years that predict all-cause mortality and changes in physical and mental health in later life. In a register- based study of 13,345 men and women, and in a longitudinal study in a sub-sample of 1600 people, we will examine how change in height and body mass index between different ages is related to mortality from cardiovascular and non-cardiovascular causes and to indices of physiological, mental and biochemical health. PUBLIC HEALTH RELEVANCE: We propose that the maternal and early postnatal environments establish vulnerability to chronic disease in old age, and determine elderly people's ability to sustain their health. An understanding of this may make it possible to identify elderly people who are at risk of physical or mental deterioration, and to prolong healthy life.

描述（由申请人提供）：在任何社会经济地位水平中，寿命都有很大差异。我们的假设是这种变异是在发育过程中编程的。我们认为，不良的宫内营养和不良的儿童生活条件会引发病理过程，并永久性地改变身体的结构和功能，使其在产后生活中容易受到压力源的影响。由于宫内营养取决于母亲一生的营养，我们的研究结果将量化对女孩和年轻女性的营养和成长的投资将如何延长下一代的寿命。赫尔辛基出生队列研究涉及 20,000 人，是世界上唯一已知的数据集，其中包括孕妇体型、出生体型、婴儿和儿童生长以及临终者的生活条件。该队列包括每五年一次的全国人口普查记录的详细社会经济数据。我们还提出，老年时维持身心健康的能力是在发育过程中规划的。我们将探讨宫内营养和儿童生活条件对老年复原力的影响；我们将研究是否存在对此至关重要的增长时期。这将为促进生命早期福祉和保护弱势老年人的预防策略提供信息。在后续研究（不是本申请的主题）中，我们将使用已经进行的全基因组扫描来区分环境和遗传对老年复原力的影响。具体目标 1：确定孕产妇营养和儿童生活条件如何预测全因死亡率，同时考虑到晚年的社会经济条件。在两项针对 7086 名和 13,345 名男性和女性的登记研究中，我们将分别将这些早期生活影响与所有原因以及心血管和非心血管原因的死亡率联系起来。具体目标 2：确定孕产妇营养和儿童生活条件如何预测以后生活中身心健康的变化，同时考虑到成人生活方式、社会经济条件和疾病。在对 1600 人的子样本进行的纵向研究中，我们将这些早期生活影响与生理、心理和生化健康指数的变化联系起来。具体目标 3：确定从出生到 11 岁之间是否存在可预测全因死亡率以及晚年身心健康变化的关键生长时期。在一项针对 13,345 名男性和女性的登记研究以及一项针对 1600 人的子样本的纵向研究中，我们将研究不同年龄之间身高和体重指数的变化与心血管和非心血管疾病死亡率的关系。原因以及生理、心理和生化健康指标。公共卫生相关性：我们认为，孕产妇和产后早期环境容易导致老年时罹患慢性疾病，并决定老年人维持健康的能力。了解这一点可能有助于识别面临身体或精神恶化风险的老年人，并延长健康寿命。