Stomach Ghrelin Homeostasis in Aging

研究主题：#18--功能性衰老 在老龄化的人口中，生长激素(GH)的分泌和营养受到影响。GH是一个 调节身体几乎每一个组织的必需荷尔蒙。随着年龄的增长，生长激素分泌和营养的下降可能会显著降低整体身心功能和承受压力侮辱的能力。我们的长期目标是确定新的临床方法，以避免老年人类生长激素分泌和营养摄入的恶化。 新的证据支持这一假设，即垂体GH的分泌不仅受来自下丘脑的GH释放激素(GHRH)的调节，也受来自胃的Ghrelin的调节。Ghrelin是一种新的胃激素，可以刺激GH的分泌，促进食物的摄取，促进肥胖和体重增加。我们长期有效的假设是，胃Ghrelin是连接胃肠道系统的关键角色，即营养摄入与GH分泌的调节、维持体重和生长，以及胃Ghrelin-垂体GH轴受到衰老过程的影响。 对于这一提议，我们的假设是，肠道激素CCK和胰腺高血糖素对胃Ghrelin的产生和分泌的调节会随着衰老过程而改变。初步研究结果表明，胃促生长激素垂体轴受饮食摄入量、胃肠-胰腺激素、CCK和胰升糖素的影响。我们的具体目标是：目的1.验证GRELIN改变脑下垂体GH分泌的假说。目的2.验证胃促生长素稳态中与GGE相关的升高是由胰高血糖素和胆囊收缩素(CCK)调节的改变机械激活的假说。 这项研究意义重大，因为我们将确定Omach Ghrelin调节GH分泌的潜在机制，以及营养和营养激活激素在调节GH分泌中的作用。这项研究将为治疗体重减轻或增加起关键作用的衰老疾病开辟新的治疗策略。这是一个令人信服的理由来定义Ghrelin的营养调节及其在生长激素分泌、体重增加和生长中的作用。

RESEARCH TOPIC: #18 - Functional Senescence in the aging population, growth hormone (GH) secretion and nutrition are compromised. GH is an essential hormone that regulates nearly every tissue in the body. Aging associated declines in GH secretion and nutrition may contribute significantly to reductions in overall physical and mental function and ability to tolerate stress insults. Our long-term goal is to identify new clinical approaches that avert deterioration in GH iecretion and nutritional intake in aging humans. Emerging evidence supports the hypothesis that pituitary GH secretion is regulated not only by GH releasing hormone (GHRH) from the hypothalamus, but also by ghrelin from the stomach. Ghrelin is a new stomach hormone that stimulates GH secretion, food intake, adiposity and weight gain. Our long-term, working hypotheses are that stomach ghrelin is a key player in linking the gastrointestinal system, i.e., nutritional intake with regulation of GH secretion, maintenance of body weight and growth, and that the stomach ghrelin-pituitary GH axis is compromised by the aging process. For this proposal, our hypothesis is that regulation of stomach ghrelin production and secretion by the intestinal hormone cholecystokinin (CCK) and pancreatic glucagon is altered by the aging process. Preliminary findings implicate a stomach-ghrelin pituitary GH axis that is influenced by dietary intake and the gut-pancreatic hormones, CCK and glucagon. Our Specific Aims are: Aim 1. To test the hypothesis that the ging process alters the regulation of pituitary GH secretion by ghrelin. Aim 2. To test the hypothesis that ging associated elevations in stomach ghrelin homeostasis are activated mechanistically by alterations in regulation by glucagon and cholecystokinin (CCK). This research is significant because we will identify mechanisms underlying regulation of GH secretion by omach ghrelin and the role of nutrition and nutritionally activated hormones in the regulation of GH secretion. This research will open up new therapeutic strategies for treatment of diseases of aging in which weight loss or gain plays a critical role. This is a compelling reason to define nutritional regulation of ghrelin and its role ingulation of GH secretion, weight gain and growth.