SUN-042 - Two-Year Old Growth Hormone Receptor Antagonist Mice (GHA) Have Reduced Frailty and Improved Grip Strength

Growth hormone receptor antagonist (GHA) mice were first developed in the early 1990’s and played a key role in the development of Pegvisomant - the first and only FDA approved GH antagonist used for the treatment of acromegaly. Characterization of this mouse line has served as a valuable tool for evaluating the physiological effects of GHR antagonism. Important to the current study, GHA mice show signs of healthy aging as they exhibit improved cognitive function, reduced fibrosis, reduced cancer susceptibility, and protection from osteoarthritis and kidney damage. However, frailty has not been thoroughly evaluated in this mouse line. Thus, the aim of this study was to evaluate frailty in 24-month male and female GHA mice using the mouse clinical frailty index developed by Howlett and colleagues. Grip strength and body composition were also measured. While the male GHA mice had increased fat percentages, both male and female GHA mice showed significantly improved frailty scores and greater grip strength measurements. In male GHA mice, integumentary factors like loss of fur color and coat condition, indicators of discomfort like piloerection, and musculoskeletal factors like tail stiffening were all significantly improved. The presence of ocular conditions like swelling, discharge, squinting, were decreased in male GHA mice. In female GHA mice, tail stiffening was improved and there was a decrease in the occurrence of corneal opacity. Both male and female GHA mice were significantly stronger than their WT counterparts when normalizing their grip strength to their lean body mass. In summary, these findings indicate that GHR antagonism reduces frailty and improves grip strength. Overall, these findings suggest that GHR antagonism may represent a promising therapeutic avenue for mitigating frailty and enhancing functional capacity in aging populations.

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