The Developmental Origins of Disease and Deterioration in Old Age

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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.