Murine exercise models can provide information on factors that influence muscle adaptability with aging, but few translatable solutions exist. Progressive weighted wheel running (PoWeR) is a simple, voluntary, low-cost, high-volume endurance/resistance exercise approach for training young mice. In the current investigation, aged mice (22-month-old) underwent a modified version of PoWeR for 8 weeks. Muscle functional, cellular, biochemical, transcriptional, and myonuclear DNA methylation analyses provide an encompassing picture of how muscle from aged mice responds to high-volume combined training. Mice run 6-8 km/day, and relative to sedentary mice, PoWeR increases plantarflexor muscle strength. The oxidative soleus of aged mice responds to PoWeR similarly to young mice in every parameter measured in previous work; this includes muscle mass, glycolytic-to-oxidative fiber type transitioning, fiber size, satellite cell frequency, and myonuclear number. The oxidative/glycolytic plantaris adapts according to fiber type, but with modest overall changes in muscle mass. Capillarity increases markedly with PoWeR in both muscles, which may be permissive for adaptability in advanced age. Comparison to published PoWeR RNA-sequencing data in young mice identified conserved regulators of adaptability across age and muscles; this includes Aldh1l1 which associates with muscle vasculature. Agrn and Samd1 gene expression is upregulated after PoWeR simultaneous with a hypomethylated promoter CpG in myonuclear DNA, which could have implications for innervation and capillarization. A promoter CpG in Rbm10 is hypomethylated by late-life exercise in myonuclei, consistent with findings in muscle tissue. PoWeR and the data herein are a resource for uncovering cellular and molecular regulators of muscle adaptation with aging.
Background Patellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5–15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return to activity. Methods/design This is a parallel-group, superiority, randomized, double-blinded, placebo-controlled clinical trial at the University of Kentucky, sports medicine clinic that aims to recruit 78 patients with acute patellar dislocations randomly allocated into two groups: (1) sham BFRT and (2) BFRT. Both groups will receive the current standard of care physical therapy 3 times per week for up to 9 weeks. Physical therapy sessions will consist of typical standard of care treatment followed by BFRT or sham BFRT. Primary outcomes include the Norwich Patellar Instability Scale, quadriceps strength, and imaging and biochemical biomarkers of cartilage degradation. Discussion The current standard of care for non-operative treatment of patellar instability is highly variable does not adequately address the mechanisms necessary to restore lower extremity function and protect the long-term health of articular cartilage following injury. This proposed novel intervention strategy uses an easily implementable therapy to evaluate if BFRT significantly improves patient-reported outcomes, function, and joint health over the first year of recovery. Trial registration Blood Flow Restriction Training, Aspiration, and Intraarticular Normal Saline (BRAINS) NCT04554212. Registered on 18 September 2020.
Skeletal muscle plasticity in response to countless conditions and stimuli mediates concurrent functional adaptation, both negative and positive. In the clinic and the research laboratory, maximal muscular strength is widely measured longitudinally in humans, with knee extensor musculature the most reported functional outcome.Pathology of the knee extensor muscle complex is well documented in aging, orthopedic injury, disease, and disuse; knee extensor strength is closely related to functional capacity and injury risk, underscoring the importance of reliable measurement of knee extensor strength. Repeatable, in vivo assessment of knee extensor strength in pre-clinical rodent studies offers valuable functional endpoints for studies exploring osteoarthritis or knee injury. We report an in vivo and non-invasive protocol to repeatedly measure isometric peak tetanic torque of the knee extensors in mice across time. We demonstrate consistency using this novel method to measure knee extensor strength with repeated assessment in multiple mice producing similar results.
Objective Long-term quadriceps femoris muscle performance and physical function after surgical repair of a lower extremity fracture remains largely undefined. The purpose of this study was to investigate between-limb differences in quadriceps performance 12 months after surgical fixation of a lower extremity fracture. It was hypothesized that the injured limb would be significantly weaker, have a lower rate of torque development, and that there would be a reduced step-down performance compared to the uninjured limb 12 months after surgery. Additionally, this study sought to identify demographic, surgical, and psychological factors associated with poor quadriceps function 12 months after surgery. Methods Quadriceps performance was measured bilaterally in 95 participants (49 female), aged 42 (SD = 14.5) years, 12 months after surgical fixation of a lower extremity fracture. Isometric quadriceps strength and rate of torque development were quantified using isometric dynamometry, and a timed step-down test was used to evaluate quadriceps performance. Independent predictor variables from the time of surgery were extracted from participants’ medical records. Kinesiophobia was screened at the time of testing. Wilcoxon signed-rank tests and linear regression analyses were used to assess between-limb differences in quadriceps performance and to determine factors associated with quadriceps performance 12 months after surgery. Results Significant between-limb differences in each measure of quadriceps performance were identified (peak torque involved: 1.37 [0.71] Nm*kg−1; uninvolved: 1.87 [0.74] Nm*kg−1; rate of torque development involved: 4.16 [2.75] Nm*kg−1*s−1; uninvolved: 6.10 [3.02] Nm*kg−1*s−1; and single-leg step-downs involved: 12.6 [5.0]; uninvolved: 21.7 [14.8]). Female sex, external fixation, and kinesiophobia at 12 months were associated with reduced after-surgery quadriceps performance outcomes. Conclusion Quadriceps performance is impaired 12 months after surgical repair of a lower extremity fracture, particularly in females, in cases requiring external fixation, and in those with higher kinesiophobia 12 months after surgery. Impact Because long-term quadriceps weakness negatively impacts functional mobility, targeted strengthening should be emphasized after surgical repair of lower extremity fracture.
baseline, there were no significant differences among groups for DI o [median values ranged from 1.97 (3.00) mM -1 for LM to 2.48 (3.14) mM -1 for HV]. After 6 months of exercise training, only the CL group significantly improved DI o [0.71 (0.28-1.15) mM -1 ;p=0.002]. Within-group changes for the exercise-only groups were 0.10 (-0.68-0.87) mM -1 for LM; -0.19 (-0.73-0.34) mM -1 for HM; and -0.41 (-0.83-0.02) mM -1 for HV. The Kruskal-Wallis test revealed changes in DI o were significantly better for the CL group compared to both high amount groups. CONCLUSIONS: For adults with prediabetes, combining a dietary intervention and weight loss with aerobic exercise improves DI o . Compared to findings from previous STRRIDE studies, improving β-cell function appears to be more challenging with aerobic exercise alone for those with a glycemic status closer to type 2 diabetes. Supported by NIH R01DK081559 828 Rate Of Torque Development Improvements Are Greatest Within First 2 Weeks Of Power-based Training
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