Abstract
Skeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progression of human musculoskeletal aging is slow, researchers rely on rodent models to identify mechanisms and test interventions. The Dunkin Hartley guinea pig is an outbred strain that begins developing primary osteoarthritis by 4 months of age with a progression and pathology similar to aging humans. The purpose of this study was to determine if skeletal muscle remodeling during the progression of osteoarthritis in these guinea pigs resembles musculoskeletal aging in humans. We compared Dunkin Hartley guinea pigs to Strain 13 guinea pigs, which develop osteoarthritis much later in the lifespan. We measured myofiber type and size, muscle density, and long-term fractional protein synthesis rates of the gastrocnemius and soleus muscles in 5, 9, and 15-month-old guinea pigs. There was an age-related decline in skeletal muscle density, a greater proportion of smaller myofibers, and a decline in type II concomitant with a rise in type I myofibers in the gastrocnemius muscles from Dunkin Hartley guinea pigs only. These changes were accompanied by age-related declines in myofibrillar and mitochondrial protein synthesis in the gastrocnemius and soleus. Collectively, these findings suggest Dunkin Hartley guinea pigs experience myofiber remodeling alongside the progression of osteoarthritis, consistent with human musculoskeletal aging. Thus, Dunkin Hartley guinea pigs may be a model to advance discovery and therapeutic development for human musculoskeletal aging.
Highlights
Musculoskeletal aging broadly describes the progressive decline in skeletal muscle, bone, tendon, and articular cartilage that contributes to disability, chronic disease, and impaired quality of life in older adults (Roux et al, 2005; Landi et al, 2013; Batsis et al, 2014; Yokota et al, 2015; Williams et al, 2018; Ogawa et al, 2018)
Obtaining a full understanding of mechanisms contributing to musculoskeletal decline is hampered by complex contributions from systemic components including skeletal muscle, bone, articular cartilage, and tendon, and by the relative absence of preclinical models that closely and comprehensively model the human musculoskeletal aging phenotype
For the first time, evidence of skeletal muscle remodeling in Dunkin Hartley guinea pigs that is consistent with those observed during musculoskeletal aging in humans
Summary
Musculoskeletal aging broadly describes the progressive decline in skeletal muscle, bone, tendon, and articular cartilage that contributes to disability, chronic disease, and impaired quality of life in older adults (Roux et al, 2005; Landi et al, 2013; Batsis et al, 2014; Yokota et al, 2015; Williams et al, 2018; Ogawa et al, 2018). The projected increase in the aged population will lead to a growing number of individuals living with skeletal muscle dysfunction, and overall musculoskeletal decline (Dhillon and Hasni, 2017), leading to an increased economic burden (Goates et al, 2019). Given both the health and financial burdens, understanding the etiology and discovering therapies to prevent or mitigate age-related skeletal muscle decline, and promote overall musculoskeletal health with aging, is critical
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