AGED-RODENT MODELS OF LONG-TERM GROWTH-HORMONE THERAPY - LACK OF DELETERIOUS EFFECT ON LONGEVITY

Studies were carried out to examine the effects of long-term recombina nt human growth hormone (GH) therapy on longevity in rodents. In the f irst study, 150 18 month-old female F344 rats were divided into three groups of 50 rats per group: Group 1, solvent vehicle; Group 2, 10 mu g GH/kg body weight three times per week; Group 3, 50 mu g GH/kg body weight three times per week. GH and solvent vehicle therapies were sta rted at 18 months of age and continued until all the animals died spon taneously. Serum insulin-like growth factor (IGF)-I was measured at 18 and 29 months of age and on 3-month-old rats. Serum IGF-I level decre ased between 3 and 29 months of age. GH therapy reversed the decrease in a dose-dependent manner, with the 50 ag GH dose returning the serum IGF-I level to that of 3-month-old animals. However, statistical anal ysis revealed no significant effect of GH therapy on median life span, 10th percentile life span, or maximum life span. Similar observations on longevity were made on aged F344 male rats and on aged Balb/c mice , even when the dose of GH was increased to 1.0 mg/kg body weight two times per week. The main pathologic lesions in control animals were ne phropathy, cardiomyopathy, leukemia, and testicular interstitial cell tumor; the prevalence of these lesions was not significantly altered b y GH therapy. We conclude that long-term low-dose GH therapy that incl udes doses in the range that is given to humans in clinical trials in GH deficiency and to revert age-related physiologic declines has no ov ert deleterious effects on longevity and pathology in aged rodents.