The Developmental Origins of Disease and Deterioration in Old Age

老年疾病和恶化的发育起源

• 批准号: 8324214
• 负责人: Kent L.R. Thornburg
• 金额: $ 16.72万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8324214
• 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 Growth; 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; physical conditioning; postnatal; programs; public health relevance; resilience; response; socioeconomics; stressor

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下，寿命都有很大的差异。我们的假设是，这种变化是在发展过程中编程。我们认为，宫内营养不良和儿童生活条件差启动病理过程，并永久改变身体的结构和功能的方式，使其容易受到压力在产后生活。由于子宫内营养是由母亲一生的营养决定的，我们的研究结果将量化对女孩和年轻妇女营养和成长的投资将如何增加下一代的寿命。赫尔辛基20,000人出生队列研究是世界上唯一已知的数据集，包括产妇体型，出生尺寸，婴儿和儿童成长以及现在处于生命尽头的人的生活条件。该队列包括每5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，在老年维持身心健康的能力是在发展过程中编程的。我们将探讨宫内营养和童年生活条件对老年恢复力的影响;我们将研究是否有生长期对此至关重要。这将为促进生命早期福祉和保护弱势老年人的预防战略提供信息。在随后的研究中，这不是本申请的主题，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恢复力的影响。具体目标1：确定母亲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。在两项基于登记的研究中，7086名和13,345名男性和女性，我们将这些早期生命影响与所有原因以及心血管和非心血管原因的死亡率分别联系起来。具体目标二：确定母亲营养和童年生活条件如何预测晚年身心健康的变化，同时考虑到成年生活方式、社会经济条件和疾病。在一项对1600人的子样本的纵向研究中，我们将这些早期生活的影响与生理，心理和生化健康指数的变化联系起来。具体目标3：确定在出生到11岁之间是否存在关键的生长期，以预测全因死亡率以及以后生活中身心健康的变化。在一项对13,345名男性和女性进行的基于登记的研究中，以及在一项对1600人进行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如何与心血管和非心血管原因的死亡率以及生理、心理和生化健康指数相关。 公共卫生相关性：我们认为，产妇和产后早期环境建立在老年慢性疾病的脆弱性，并确定老年人的能力，以维持他们的健康。了解这一点，就有可能确定哪些老年人有身体或精神退化的危险，并延长健康的寿命。