Authors
Kalu DN. Orhii PB. Chen C. Lee DY. Hubbard GB. Lee S. Olatunji-Bello Y.
Institution
Department of Physiology, The University of Texas Health Science Center at
San Antonio, 78284-7756, USA. kalu@uthscsa.edu
Title
Aged-rodent models of long-term growth hormone therapy: lack of deleterious
effect on longevity.
Source
Journals of Gerontology. Series A, Biological Sciences & Medical Sciences.
53(6):B452-63, 1998 Nov.
Abstract
Studies were carried out to examine the effects of long-term recombinant
human growth hormone (GH) therapy on longevity in rodents.
In the first 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 microg GH/kg body weight three times per week; Group 3, 50 microg
GH/kg body weight three times per week. GH and solvent vehicle therapies were
started at 18 months of age and continued until all the animals died
spontaneously. 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 decreased
between 3 and 29 months of age. GH therapy reversed the decrease in a
dose-dependent manner, with the 50 microg GH dose returning the serum IGF-I
level to that of 3-month-old animals. However, statistical analysis 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 nephropathy, cardiomyopathy, leukemia, and testicular
interstitial cell tumor; the prevalence of these lesions was not
significantly altered by GH therapy. We conclude that long-term low-dose GH
therapy that includes doses in the range that is given to humans in clinical
trials in GH deficiency and to revert age-related physiologic declines has no
overt deleterious effects on longevity and pathology in aged
rodents.