SAT-047 - Built for Growth, Prone to Frailty: A Longitudinal Frailty Study in Bovine Growth Hormone (Bgh) Transgenic Mice

Frailty characterizes aging trajectories and is used to differentiate between chronological and biological age. Frail individuals are more susceptible to adverse health outcomes than healthy, non-frail individuals of the same age. This frail phenotype is commonly observed in patients with acromegaly. Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, often leading to shortened lifespan, among many other negative health pathologies. This study investigated the onset and progression of frailty in bovine growth hormone (bGH) mice, a mouse model of acromegaly, to better understand the correlation between chronic excessive GH action and accelerated biological aging. bGH mice exhibit a shortened lifespan with significant organ dysfunction, emphasizing the importance of investigating the onset and progression of frailty. Male and female bGH and WT mice (n=8/sex/genotype) were evaluated via body composition analysis, frailty index assessment, grip strength measurements, and serum collection monthly from 5-14 months of age. Our results showed that bGH mice are significantly more susceptible to frailty starting at 5 months of age and progress to a more severe phenotype at an accelerated rate compared to WT mice. Notable deficits in male and female bGH mice were particularly apparent in the musculoskeletal system and included kyphosis, tail stiffening, and gait disorders. Interestingly, female mice regardless of genotype, were protected from frailty more than their male counterparts. Despite having a greater body mass and lean mass, bGH mice of both sexes displayed significantly lower grip strength compared to their WT counterparts. Overall, these findings indicate that chronic GH/IGF-1 excess drives premature and accelerated frailty in bGH mice, highlighting the need for early therapeutic interventions for conditions of excess in the GH/IGF-1 axis, particularly to address notable musculoskeletal deficits, which may have implications for patients with acromegaly. Further investigation into the mechanisms driving frailty and potential biomarkers underlying GH-associated frailty in serum are planned, and samples collected over the duration of the study will be utilized.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*