THE ROLE OF GROWTH HORMONE IN THE AGING PROCESS

生长激素在衰老过程中的作用

基本信息

批准号：
3115051
负责人：
ROBERT M BLIZZARD
金额：
$ 16.83万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1987-11-30
项目状态：
已结题

项目摘要

Our hypothesis is that GH deficiency may be responsible for some physiologic changes associated with aging, including loss of mineral from bone, decreased skin elasticity and loss of lean body mass. The specific aims of the project are: (1) To establish the age(s) at which a significant decrease in somatomedin-C (Sm-C) and mean integrated concentrations of serum GH levels (ICGH) occurs in normal males and females. (2) To determine if males Greater than 50 years of age with low ICGH & Sm-C levels in plasma release GH from the pituitary when given pharmacologic stimuli which cause GH release in children & young adults. (3) To determine the acute metabolic responses relating to N2 and Ca balance, lipid and lipoprotein concentrations, glucose tolerance, hydroxyproline excretion, and to Sm-C concentrations, when GH is given for 5-7 days to normal males (Greater than 45 years), with low GH and Sm-C levels, as compared to the response of young adults who are GH deficient. (4) To establish the effect of daily GH administration for 3 years on the body composition of GH deficient subjects 20-30 years of age (Group HA) and on the body composition of normal males Greater than 45 years of age (Group O). Groups HA and O will be divided into 2 groups (10 in HA1 & HA2, 15 in 01 & 02). 01 & HA1 will receive GH each day. 02 & HA2 will serve as controls. Parameters of body composition to be assessed include total body N2, Ca, fat, lean body mass, bone density, total body water, and skin composition. Skin from punch biopsies will be analyzed for the type and quantity of Type I & III collagen by SDS electrophoresis; fibronectin, laminin, and Type IV collagen by immunofluorescent antibody techniques; levels of hydroxyproline and hydroxylysine by AA analysis: reducible cross links in collagen by chromatography; measurement of fiber bundle diameter and orientation by electron microscopy; and fibronectin levels in plasma. Comparison of all body composition studies will be made between individuals in groups and between groups to ascertain changes with aging and alterations as a result of long term GH administration. In addition to the scientific knowledge gained, it is conceivable that restoration of body tissues to an earlier state could occur with GH administration in older individuals.

我们的假设是GH缺乏症可能是某些人的原因与衰老相关的生理变化，包括从骨骼，皮肤弹性降低和瘦体重的损失。该项目的具体目的是：（1）确定年龄体系C-C（SM-C）和平均整合的显着降低血清GH水平（ICGH）的浓度发生在正常男性中，并且女性。（2）确定男性是否大于50岁给出垂体时等离子体释放GH的ICGH＆SM-C水平在儿童和年轻人中导致GH释放的药理刺激。（3）确定与N2和CA有关的急性代谢反应平衡，脂质和脂蛋白浓度，葡萄糖耐受性，当GH给出GH时，羟基的排泄和SM-C浓度正常男性（大于45年）的5-7天，低GH和SM-C 与GH不足的年轻人的反应相比，水平。（4）建立每日GH管理的影响3年 GH缺乏受试者的身体组成20-30岁（组HA）和关于正常雄性的身体成分大于45岁（组 o）。 HA和O组将分为2组（HA1和HA2中的10组，15 in 01＆02）。 01＆ha1每天将获得GH。 02＆ha2将作为控件。要评估的身体成分参数包括总体 N2，CA，脂肪，瘦体重，骨密度，全身水和皮肤作品。将分析来自打孔活检的皮肤的类型和 SDS电泳的I型胶原蛋白量的数量；纤连蛋白，层粘连蛋白和IV型胶原蛋白通过免疫荧光抗体技术；通过AA分析：可还原的杂交水平色谱中的胶原蛋白链接；纤维束直径的测量和电子显微镜方向；血浆中的纤连蛋白水平。将在个人之间进行所有身体组成研究的比较分组和组之间，以确定衰老和长期GH给药的改变。除了获得科学知识外，可以想象 GH可能会恢复身体组织到早期状态在老年人中给药。