The purpose of this study was to test the hypothesis that macrophage polarization is altered in old compared to young skeletal muscle, possibly contributing to the poor satellite cell response observed in older muscle tissue. Muscle biopsies were collected prior to and at 3, 24, and 72 h following a muscle‐damaging exercise in young and old individuals. Immunohistochemistry was used to measure i.m. macrophage content and phenotype, and cell culture experiments tested macrophage behavior and influence on primary myoblasts from older individuals. We found that macrophage infiltration was similar between groups at 24 (young: 3712 ± 2407 vs. old: 5035 ± 2978 cells/mm3) and 72 (young: 4326 ± 2622 vs. old: 5287 ± 2248 cells/mm3) hours postdamage, yet the proportion of macrophages that expressed the proinflammatory marker CD11b were markedly lower in the older subjects (young: 74.5 ± 15 vs. old: 52.6 ± 17%). This finding was coupled with a greater overall proportion of CD206+, anti‐inflammatory macrophages in the old (group: P = 0.0005). We further demonstrate in vitro that proliferation, and in some cases differentiation, of old primary human myoblasts increase as much as 30% when exposed to a young macrophage‐conditioned environment. Collectively, the data suggest that old macrophages appear less capable of adapting and maintaining inflammatory function, which may contribute to poor satellite cell activation and delayed recovery from muscle damage.—Sorensen, J. R., Kaluhiokalani, J. P., Hafen, P. S., Deyhle, M. R., Parcell, A. C., Hyldahl, R. D. An altered response in macrophage phenotype following damage in aged human skeletal muscle: implications for skeletal muscle repair. FASEB J. 33,10353–10368 (2019). http://www.fasebj.org

Epidemiological data indicate that repeated heat stress improves cardiovascular health, making passive heat therapy (PHT) a potential alternative for those unable to exercise. Few studies to date have examined the potential exercise mimetic effects in humans, and it is unclear how adaptations compare in magnitude to exercise training. OBJECTIVE: To examine the effects of 6 weeks of localized, muscle-focused PHT on resistance artery vascular function, exercise hemodynamics, and exercise performance relative to the adaptations observed following high-intensity aerobic exercise training focused on the same muscles. HYPOTHESIS: 6 weeks of PHT, applied through pulsed shortwave diathermy (2 hr, 3 days/week), would increase resistance artery function, improve exercise hemodynamics, and enhance exercise performance more than a sham treatment, but less than single-leg knee extension (KE) exercise training (EX; 40 min, 3 days/week). We also hypothesized that these functional adaptations would be accompanied by increased skeletal muscle capillarity. METHODS: We randomized 34 sedentary but otherwise healthy, young adults (ages 18–36; n = 17 female, 17 male) to receive PHT, EX, or sham heating sessions (SHAM; 2 hr, 3 days/week) over 6 weeks. Vascular function was determined through the blood flow response during both a passive leg movement (PLM) assessment and a knee extension graded exercise test (GXTmax). Muscle biopsies were taken from the vastus lateralis at baseline and after 6 weeks of intervention. RESULTS: Peak muscle treatment temperature was significantly different between all groups with PHT exhibiting a higher peak temperature (~40.80°C) than those in the EX (~37.75°C, P<0.001) and SHAM groups (~36.10°C, P<0.001). Peak blood flow during PLM increased to the same extent (P=0.625) in both the EX (~10.5% increase, P=0.009) and PHT groups (~8.5% increase, P=0.044); but tended to decrease in the SHAM group (P=0.087). KE peak flow increased in EX (~19%, P=0.005), but did not change in PHT (P=0.523) and decreased in SHAM (~7%, P=0.020). Peak vascular conductance during KE significantly increased by ~25% in EX (P=0.030) and PHT (P=0.012). KE peak power increased in EX by ~27% (P=0.001) but did not significantly change in PHT(P=0.175) and SHAM groups (P=0.111). EX, but not PHT or SHAM increased muscle capillary-to-fiber ratio (P = 0.0003), capillary density (P = 0.0428), and the Capillary to Fiber Perimeter Exchange Index (P = 0.0089). CONCLUSIONS: 6 weeks of localized PHT, when applied to young healthy individuals, improved resistance artery function at rest and during exercise to the same extent as exercise training. However, PHT did not lead to increased KE peak flow, microvascular remodeling, or improved exercise performance. Therefore, PHT mimics many, but not all the vascular benefits of exercise training. Further research is necessary to determine the mechanism by which 6 weeks of PHT led to improved vascular function at rest and during exercise. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

AIM: Mild heat stress can improve mitochondrial respiratory capacity in skeletal muscle. However, long-term heat interventions are scarce, and the effects of heat therapy need to be understood in the context of the adaptations which follow the more complex combination of stimuli from exercise training. The purpose of this work was to compare the effects of 6 weeks of localized heat therapy on human skeletal muscle mitochondria to single-leg interval training. METHODS: Thirty-five subjects were assigned to receive sham therapy, short-wave diathermy heat therapy, or single-leg interval exercise training, localized to the quadriceps muscles of the right leg. All interventions took place 3 times per week. Muscle biopsies were performed at baseline, and after 3 and 6 weeks of intervention. Mitochondrial respiratory capacity was assessed on permeabilized muscle fibers via high-resolution respirometry. RESULTS: The primary finding of this work was that heat therapy and exercise training significantly improved mitochondrial respiratory capacity by 24.8 ± 6.2% and 27.9 ± 8.7%, respectively (p < 0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p < 0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. CONCLUSION: Six weeks of muscle-localized heat therapy significantly improves mitochondrial respiratory capacity, comparable to exercise training. However, unlike exercise, heat does not improve fatty acid oxidation capacity.

No abstract

PURPOSE:The gut microbiota modulates a variety of physiologic processes. Recent studies from our group have shown that regular endurance exercise alters the composition of the gut microbiome and metabolome in mice and humans, and we hypothesized that the presence of microbes would affect endurance training adaptations in muscular endurance capacity, mitochondrial activity and gene expression in mice. METHODS:To discern differences in adaptations from 6 wks of voluntary wheel running (VWR), we depleted microbes with antibiotics (ABX) and used germ free (GF) mice to compare to control (CON). Male and female C57Bl/6 mice of all groups underwent daily VWR or sedentary (SED) conditions in a 2 x 3 design (VWR/SED, CON/ABX/GF, n=56). After the intervention, treadmill endurance was assessed and gastrocnemius and soleus tissue were harvested and analyzed for activity of key Krebs cycle enzyme Citrate Synthase (CS) and expression of genes indicating mitochondrial adaptations respectively. RESULTS: Two way ANOVA revealed that VWR increased treadmill endurance, ABX had no effect, and that GF status significantly reduced performance. Additionally, VWR increased Citrate Synthase enzyme activity in gastrocnemius muscle tissue in all groups, and ABX and GF status did not reduce VWR's effect or have an effect of their own. VWR also tended to increase expression of genes associated with increased mitochondrial activity (PGC-1α, CS, Succinate Dehydrogenase) in soleus tissue, but ABX had no effect on these observations. CONCLUSIONS: We conclude that ABX treatment and GF status do not affect VWR induced adaptations in endurance capacity, gastrocnemius mitochondrial activity or expression of metabolic genes in soleus tissue, but that GF status significantly hinders endurance capacity. This indicates that removing gut microbes does not inhibit muscular endurance training adaptations, but that germ free mice possess hindered endurance exercise capacity.