An Evaluation Of Skeletal Muscle Aging Using A Novel Guinea Pig Model

Abstract

Maintenance of the musculoskeletal system is critical to prevent falls and loss of mobility with aging. Sarcopenia, the age-related loss of muscle mass and function, affects 10% of those over 65 years and as much as 50% of people over 80 years of age. Aging is a major risk factor for osteoarthritis (OA) which is characterized by a concomitant loss of skeletal muscle, further contributing to decreased mobility. The “inflammaging” phenotype, (i.e., age-related increases in low-grade inflammation and oxidative stress) is common to both OA and sarcopenia. While progress has been made in understanding the mechanisms of sarcopenia a preclinical model that capitulates human conditions is lacking. Dunkin Hartley (DH) guinea pigs rapidly and spontaneously develop primary knee OA beginning at about 4 months of age. Thus, we speculate that DH guinea pigs may also be a valuable model of sarcopenia. PURPOSE: To determine if DH guinea pigs can serve as a model to understand human skeletal muscle aging. METHODS: We compared skeletal muscle age-related changes in the gastrocnemius (GAS) and soleus (SOL) from 5, 9, and 15-mo DH guinea pigs. We also compared these changes to a strain of guinea pig, strain 13, that does not develop knee OA at an early age. Magnetic resonance imaging was used to examine volume and then used to calculate muscle density. Immunofluorescent histochemistry was used to assess myofiber size distribution. Formalin fixed muscles were stained in India ink to measure pennation angle. Fibrosis was assessed using muscles paraffin embedded and stained with Masson’s Trichrome to quantify % collagen. Analyses are ongoing to identify if DH pigs are characterized by an inflammaging phenotype similar to aging human muscle. RESULTS: DH guinea pigs had a significant decrease in GAS density between 5 and 15-mo that was not present in the SOL (p<0.05). Both in the GAS and SOL, DH guinea pigs also demonstrated a shift towards a smaller average myofiber size with age. However, there were no age-related changes in pennation angle or fibrosis. CONCLUSION: Based on these analyses, the DH guinea pig appears to be a potentially valuable model of musculoskeletal aging. Identifying a model to study muscular aging that mimics human conditions but in a shortened time frame, will potentially allow for effective screening and treatment interventions.