The effects of early life nutritional and hormonal signals on mammalian aging (Health Disparities Admin Supp)

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DESCRIPTION (provided by applicant): It is well accepted that early developmental events can have profound long-term effects on health and diseases. For example, Intrauterine growth retardation, maternal nutrition deficiency represent risk factors for development of diseases including cardiovascular diseases, type 2 diabetes and metabolic syndrome. However, it is unknown whether (or to what extent) these early life events also influence mammalian aging and longevity. On the basis of most recent findings, we hypothesize that the first few weeks of postnatal life represents a critical "developmental window" in which the rate of aging is set by a combination of factors including hormonal levels and nutritional signals. To uncover mechanisms responsible for these early life events, we will try to understand when and how early hormonal signaling can have a profound effect on aging rate, lifespan and age-associated metabolic changes. We will also examine the effects of calorie restriction (CR) during early postnatal life. Moreover, we will compared the early life CR effects on the GH-deficient and resistant mice. The results will begin to fill the gap in the present understanding of the developmental influences on aging and metabolism and set the stage for addressing broader questions of major public health significance. To ensure the success of this career development grant, I have assembled a team of experts in the areas that are proposed to be studied in this proposal. All of the mentors have considerable experience in writing and evaluating grant proposals, as well as in researching diverse areas of mammalian aging. We have also developed a complete plan for enhancing my research skills and pushing my career forward.