Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2‐related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis. We hypothesized daily treatment with a purported Nrf2 activator, PB125, in Hartley guinea pigs, a model of musculoskeletal decline, would attenuate the progression of skeletal muscle mitochondrial dysfunction and impaired proteostasis and preserve musculoskeletal function. We treated 2‐ and 5‐month‐old male and female Hartley guinea pigs for 3 and 10 months, respectively, with the phytochemical compound PB125. Longitudinal assessments of voluntary mobility were measured using Any‐MazeTM open‐field enclosure monitoring. Cumulative skeletal muscle protein synthesis rates were measured using deuterium oxide over the final 30 days of treatment. Mitochondrial oxygen consumption in soleus muscles was measured using high resolution respirometry. In both sexes, PB125 (1) increased electron transfer system capacity; (2) attenuated the disease/age‐related decline in coupled and uncoupled mitochondrial respiration; and (3) attenuated declines in protein synthesis in the myofibrillar, mitochondrial and cytosolic subfractions of the soleus. These effects were not associated with statistically significant prolonged maintenance of voluntary mobility in guinea pigs. Collectively, treatment with PB125 contributed to maintenance of skeletal muscle mitochondrial respiration and proteostasis in a pre‐clinical model of musculoskeletal decline. Further investigation is necessary to determine if these documented effects of PB125 are also accompanied by slowed progression of other aspects of musculoskeletal dysfunction. Key points Aside from exercise, there are no effective interventions for musculoskeletal decline, which begins in the fifth decade of life and contributes to disability and cardiometabolic diseases. Targeting both mitochondrial dysfunction and impaired protein homeostasis (proteostasis), which contribute to the age and disease process, may mitigate the progressive decline in overall musculoskeletal function (e.g. gait, strength). A potential intervention to target disease drivers is to stimulate nuclear factor erythroid 2‐related factor 2 (Nrf2) activation, which leads to the transcription of genes responsible for redox homeostasis, proteome maintenance and mitochondrial energetics. Here, we tested a purported phytochemical Nrf2 activator, PB125, to improve mitochondrial function and proteostasis in male and female Hartley guinea pigs, which are a model for musculoskeletal ageing. PB125 improved mitochondrial respiration and attenuated disease‐ and age‐related declines in skeletal muscle protein synthesis, a component of proteostasis, in both male and female Hartley guinea pigs.

Objective: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn. Methods: Ten 12-month-old male Hartley guinea pigs—which characteristically have moderate to advanced OA at this age—were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression. Results: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups. Conclusion: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

Background: The purpose of this study was to examine the accuracy of heart rate (HR) and energy expenditure (EE) estimated by the Apple Watch Series 1 worn both on the wrist and the upper arm. Methods: Thirty healthy, young adults (15 females) wore the two monitors while participating in a maximal exercise test. Criterion measures were obtained from the Parvo Medics TrueOne 2400 Metabolic Cart and an electrocardiograph. Results: The HR estimations of the arm-worn (AW) Apple Watch had the highest agreement with the electrocardiogram, with mean absolute percent error (MAPE) of <2.5% for the entire sample, for males, and for females, at all exercise intensities. The HR estimations of the wrist-worn Apple Watch had MAPEs ranging from 3.61% (females at very light intensity) to 14.97% (males at very vigorous intensity). When estimating EE for total exercise bout in the entire sample, the arm-worn Apple Watch overestimated EE, with a MAPE of 39.63%, whereas the wrist-worn underestimated EE, with a MAPE of 32.28%. Both the arm- and wrist-worn overestimated EE for females and underestimated EE for males. Conclusion: Wearing the Apple Watch Series 1 on the upper arm versus the wrist improves the MAPE for HR estimations, but does not improve MAPE for the EE calculations when compared to a criterion measure.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression.

Background: The infrapatellar fat pad (IFP) is the largest adipose deposit in the knee; however, its contributions to the homeostasis of this organ remain unknown. To determine the influence of this depot on joint health, this study determined the progression of osteoarthritis (OA) following excision of the IFP in a rodent model of naturally-occurring disease. Methods: Male Dunkin-Hartley guinea pigs (n=10) received surgical removal of the IFP in one knee at 3 months of age; contralateral knees received sham surgery as matched internal controls. Treadmill-based gait analysis was performed prior to IFP removal and monthly thereafter. Animals were harvested at 7 months of age. Both knees were processed for microcomputed tomography (microCT), histopathology, transcript expression analyses, and immunohistochemistry (IHC). Results: Fibrous connective tissue (FCT) developed in place of the native fat pad. Gait demonstrated no significant differences between IFP removal and contralateral limbs. MicroCT OA scores were improved in knees with the FCT. Histopathology confirmed maintenance of articular cartilage structure, proteoglycan content, and chondrocyte cellularity in FCT-containing knees. Transcript analyses revealed decreased expression of adipose-related molecules and inflammatory mediators in FCTs compared to IFPs. This was corroborated via IHC for select inflammatory mediators. Discussion/Conclusion: Formation of the FCT resulted in reduced OA-associated changes in both bone and cartilage. A decrease in inflammatory mediators at transcript and protein levels may be associated with these improvements. The IFP may therefore play a role in the pathogenesis of knee OA in this strain, with removal prior to disease onset appearing to have short-term benefits.