The effects of early life nutritional and hormonal signals on mammalian aging

生命早期营养和激素信号对哺乳动物衰老的影响

• 批准号: 8762628
• 负责人: Liou Sun
• 金额: $ 14.69万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8762628
• 关键词: Address; Adipose tissue; Affect; Aftercare; Age; Age-Months; Aging; Aging-Related Process; American; Applications Grants; Area; Biological Preservation; Caloric Restriction; Cardiovascular Diseases; Characteristics; Development; Disease; Dose; Early Intervention; Elderly; Ensure; Environment; Evaluation; Event; Fetal Growth Retardation; Foundations; Generations; Grant; Growth Hormone Receptor; Health; Health Care Costs; Homeostasis; Hormonal; Hormones; Individual; Inflammation; Insulin; Insulin-Like Growth Factor I; Intake; Knock-out; Knockout Mice; Life; Life Cycle Stages; Long-Term Effects; Longevity; Malnutrition; Mentors; Metabolic; Metabolic syndrome; Metabolism; Modeling; Mus; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Nutritional; Oxidative Stress; Pathway interactions; Pattern; Protocols documentation; Public Health; Research; Resistance; Risk; Risk Factors; Sexual Maturation; Signal Transduction; Somatotropin; Somatotropin-Releasing Hormone; Staging; Stress; Time; Writing; age effect; age related; base; career; career development; cost effective; experience; human GHR protein; insulin signaling; mortality; mother nutrition; novel strategies; postnatal; skills; success; trait

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.

描述（由申请人提供）：人们普遍认为，早期发育事件可能对健康和疾病产生深远的长期影响。例如，宫内发育迟缓、母体营养缺乏是包括心血管疾病、2型糖尿病和代谢综合征在内的疾病发展的风险因素。然而，尚不清楚这些早期生命事件是否（或在多大程度上）也影响哺乳动物的衰老和寿命。根据最新的研究结果，我们假设出生后的前几周是一个关键的“发育窗口”，其中衰老的速度是由包括激素水平和营养信号在内的多种因素共同决定的。为了揭示这些早期生命事件的机制，我们将试图了解早期激素信号何时以及如何对衰老率，寿命和与年龄相关的代谢变化产生深远影响。我们还将研究热量限制（CR）在出生后早期的影响。此外，我们将比较GH缺陷和抗性小鼠的早期生命CR效应。这些结果将开始填补目前对衰老和新陈代谢的发育影响的理解中的差距，并为解决具有重大公共卫生意义的更广泛问题奠定基础。为了确保这一职业发展赠款的成功，我已在本提案中建议研究的领域组建了一个专家小组。所有的导师都有相当丰富的经验，在写作和评估拨款申请，以及在研究哺乳动物衰老的不同领域。我们还制定了一个完整的计划，以提高我的研究技能，推动我的职业生涯向前发展。