The Developmental Origins of Disease and Deterioration in Old Age

说明(申请人提供)：在任何水平的社会经济地位中，寿命都有很大的不同。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童年生活条件启动了病理过程，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。由于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妇女的营养和成长方面的投资将如何增加下一代的寿命。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，包括母亲的身体尺寸、出生尺寸、婴儿和儿童的发育以及现在处于生命末期的人的生活状况。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。我们还建议，在老年时保持身心健康的能力是在发育过程中编程的。我们将探索宫内营养和童年生活条件对老年韧性的影响；我们将检查是否存在对此至关重要的成长期。这将为促进早期生活幸福和保护脆弱老年人的预防战略提供参考。在随后的研究中，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韧性的影响，这些研究不是本申请的主题。具体目标1：考虑到晚年的社会经济条件，确定产妇营养和儿童生活条件如何预测所有死因。在对7086名和13,345名男性和女性进行的两项基于登记的研究中，我们将分别将这些早期生活影响与各种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：考虑到成人的生活方式、社会经济条件和疾病，确定产妇营养和童年生活条件如何预测晚年身心健康的变化。在对1600人进行的一项纵向研究中，我们将把这些对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岁之间是否存在预测全因死亡率和晚年身心健康变化的关键生长期。在一项对13,345名男性和女性进行的基于登记的研究中，在一项对1600人的子样本进行的纵向研究中，我们将检查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死亡率以及生理、心理和生化健康指数的关系。 公共卫生相关性：我们建议母亲和出生后早期环境建立老年对慢性病的脆弱性，并确定老年人维持健康的能力。了解这一点可能有助于识别有身体或精神恶化风险的老年人，并延长健康的生命。

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.