Phytochemical compound, PB125, improved mechanisms of proteostasis in a guinea pig model of musculoskeletal decline 

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Presenter(s)

Josh Survis

Abstract or Description

Protein homeostasis (proteostasis) is the collective processes to synthesize, breakdown, and chaperone proteins. Loss of proteostasis is a hallmark of aging and drives the development of age-related chronic diseases. Specifically, loss of proteostasis drives musculoskeletal aging which includes declines in skeletal muscle, joints, and bones. Currently, there is a lack of effective treatments to slow musculoskeletal declines in older adults. One reason is the absence of effective preclinical models that recapitulate human aging. However, our lab has identified the Hartley guinea pig (HGP) as a model of musculoskeletal decline. Our lab previously demonstrated that age-related decline in skeletal muscle mitochondrial of HGPs was attenuated with the phytochemical compound, PB125, which is a nuclear factor erythroid factor 2-related factor 2 (Nrf2) activator. Nrf2 is a transcription factor at the nexus of redox homeostasis and proteostasis. The purpose of this study is to examine if PB125 treatment improves mechanisms of proteostasis in the tibialis anterior (TA) muscle. We assessed mechanisms of proteostasis with the stable-isotope deuterium to quantify rates of protein and DNA synthesis. Rates of protein synthesis were maintained in the TA in 10 mo treated HGPs. However, there was a significant decrease in DNA synthesis in PB125 treated HGPs. When examining protein synthesis in the content of cellular proliferation (DNA synthesis) we observed a greater ratio of protein synthesis to DNA synthesis in 10 mo treated HGPs indicating improved mechanisms to maintain proteostasis. These results provide a foundation for human trials with PB125 to slow the progression of musculoskeletal decline.

Mentor

Maureen Walsh