The Developmental Origins of Disease and Deterioration in Old Age

描述（由申请人提供）：在任何社会经济地位的水平上，寿命都有很大的差异。我们的假设是，这种变化是在发育过程中被编程的。我们认为，不良的宫内营养和不良的童年生活条件引发了病理过程，并永久性地改变了身体的结构和功能，使其在出生后的生活中容易受到压力源的影响。因为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在女孩和年轻女性的营养和成长方面的投资将如何延长下一代的寿命。赫尔辛基出生队列研究对2万人进行了研究，这是世界上唯一已知的数据集，包括母亲的体型、出生时的体型、婴儿和儿童的成长情况以及人们在生命结束时的生活状况。该队列包括每五年一次的全国人口普查中记录的详细社会经济数据。我们还提出，维持老年身心健康的能力是在发育过程中制定的。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；我们将研究是否存在对这一点至关重要的增长时期。这将为促进早期生活健康和保护脆弱老年人的预防战略提供信息。在随后的研究中（不是本应用的主题），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，同时考虑到以后生活中的社会经济条件。在对7086名和13345名男性和女性进行的两项基于登记的研究中，我们将把这些早期生活影响与所有原因、心血管和非心血管原因造成的死亡率分别联系起来。具体目标2：在考虑到成人生活方式、社会经济条件和疾病的情况下，确定产妇营养和儿童生活条件如何预测晚年身心健康的变化。在一项对1600人的纵向研究中，我们将把这些早期生活的影响与生理、心理和生化健康指标的变化联系起来。具体目标3：确定从出生到11岁之间是否存在预测全因死亡率和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中，以及一项针对1600人的纵向研究中，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原因导致的死亡率以及生理、心理和生化健康指数之间的关系。

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.