THE ROLE OF GROWTH HORMONE IN THE AGING PROCESS

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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.