Senolytic effects of exercise in human muscles require acute inflammation.

Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16INK4a mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage. In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16INK4a mRNA levels within muscle tissues occurred at 3 h post-exercise (-82%, p < 0.01), gradually recovering over the next 3-24 h. A concurrent reduction pattern in CD11b mRNA (-87%, p < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16INK4a mRNA and CD11b mRNA. The strong correlation (r = 0.88, p < 0.01) between p16INK4a mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.

Cordyceps sinensis accelerates stem cell recruitment to human skeletal muscle after exercise.

Cordyceps sinensis is a parasitic fungus known to induce immune responses. The impact of Cordyceps supplementation on stem cell homing and expansion to human skeletal muscle after exercise remains unexplored. In this study, we examined how pre-exercise Cordyceps supplementation influences cell infiltration, CD34+ cell recruitment, and Pax7+ cell expansion in human skeletal muscle after high-intensity interval exercise (HIIE) on a cycloergometer. A randomized, double-blind, placebo-controlled crossover study was conducted with 14 young adults (age: 24 ± 0.8 years). A placebo (1 g cornstarch) and Cordyceps (1 g Cordyceps sinensis) were administered before exercise (at 120% maximal aerobic power). Multiple biopsies were taken from the vastus lateralis for muscle tissue analysis before and after HIIE. This exercise regimen doubled the VEGF mRNA in the muscle at 3 h post-exercise (P = 0.006). A significant necrotic cell infiltration (+284%, P = 0.05) was observed 3 h after HIIE and resolved within 24 h. This response was substantially attenuated by Cordyceps supplementation. Moreover, we observed increases in CD34+ cells at 24 h post-exercise, notably accelerated by Cordyceps supplementation to 3 h (+51%, P = 0.002). This earlier response contributed to a four-fold expansion in Pax7+ cell count, as demonstrated by immunofluorescence double staining (CD34+/Pax7+) (P = 0.01). In conclusion, our results provide the first human evidence demonstrating the accelerated resolution of exercise-induced muscle damage by Cordyceps supplementation. This effect is associated with earlier stem cell recruitment into the damaged sites for muscle regeneration.

Does ergogenic effect of caffeine supplementation depend on CYP1A2 genotypes? A systematic review with meta-analysis.

BACKGROUND: The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The genetic variation of a specific gene, human cytochrome P450 enzyme 1A2 (CYP1A2) (rs762551), may be one reason for this difference. This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes' exercise performance after caffeine intake. METHODS: A literature search through 4 databases (Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure) was conducted until March 2023. The effect size was expressed as the weighted mean difference (WMD) by calculating fixed effects meta-analysis if heterogeneity was not significant (I2 ≤ 50% and p ≥ 0.1). Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2. RESULTS: The final number of studies meeting the inclusion criteria was 12 (n = 666 participants). The overall analysis showed that the cycling time trial significantly improved after caffeine intake (WMD = -0.48, 95% confidence interval (95%CI): -0.83 to -0.13, p = 0.007). In subgroup analyses, acute caffeine intake improved cycling time trial only in individuals with the A allele (WMD = -0.90, 95%CI: -1.48 to -0.33, p = 0.002), but not the C allele (WMD = -0.08, 95%CI: -0.32 to 0.17, p = 0.53). Caffeine supplementation did not influence the Wingate (WMD = 8.07, 95%CI: -22.04 to 38.18, p = 0.60) or countermovement jump test (CMJ) performance (WMD = 1.17, 95%CI: -0.02 to 2.36, p = 0.05), and these outcomes were not influenced by CYP1A2 genotype. CONCLUSION: Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation. However, compared to placebo, acute caffeine supplementation failed to increase the Wingate or CMJ performance, regardless of CYP1A2 genotype.

DNA oxidation after exercise: a systematic review and meta-analysis.

Purpose: 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a byproduct of DNA oxidation resulting from free radical attacks. Paradoxically, treatment with 8-OHdG accelerates tissue healing. The aim of this study is to quantify the 8-OHdG response after a single session of exercise in both trained and untrained adults. Methods: A systematic review and meta-analysis of exercise intervention studies measuring changes in blood 8-OHdG following resistance exercise and aerobic exercise were conducted. The literature search included Web of Science, PubMed, BASE, and Scopus, with publications up to February 2023 included. Subgroup analysis of training status was also conducted. Results: Sixteen studies involving 431 participants met the eligibility criteria. Resistance exercise showed a medium effect on increasing circulating 8-OHdG levels (SMD = 0.66, p < 0.001), which was similar for both trained and untrained participants. However, studies on aerobic exercise presented mixed results. For trained participants, a small effect of aerobic exercise on increasing circulating 8-OHdG levels was observed (SMD = 0.42; p < 0.001). In contrast, for untrained participants, a large effect of decreasing circulating 8-OHdG levels was observed, mostly after long-duration aerobic exercise (SMD = -1.16; p < 0.05). Similar to resistance exercise, high-intensity aerobic exercise (5-45 min, ≥75% VO2max) significantly increased circulating 8-OHdG levels, primarily in trained participants. Conclusion: Pooled results from the studies confirm an increase in circulating 8-OHdG levels after resistance exercise. However, further studies are needed to fully confirm the circulating 8-OHdG response to aerobic exercise. Increases in 8-OHdG after high-intensity aerobic exercise are observed only in trained individuals, implicating its role in training adaptation. Systematic Review Registration: [https://Systematicreview.gov/], identifier [CRD42022324180].

Senolytic effect of high intensity interval exercise on human skeletal muscle.

p16INK4a expression is a robust biomarker of senescence for stem cells in human tissues. Here we examined the effect of exercise intensity on in vivo senescence in skeletal muscle, using a randomized counter-balanced crossover design. Biopsied vastus lateralis of 9 sedentary men (age 26.1 ± 2.5 y) were assessed before and after a single bout of moderate steady state exercise (SSE, 60% maximal aerobic power) and high intensity interval exercise (HIIE, 120% maximal aerobic power) on a cycloergometer accumulating same amount of cycling work (in kilojoule). Increases in cell infiltration (+1.2 folds), DNA strand break (+1.3 folds), and γ-H2AX+ myofibers (+1.1 folds) occurred immediately after HIIE and returned to baseline in 24 h (p < 0.05). Muscle p16Ink4a mRNA decreased 24 h after HIIE (-57%, p < 0.05). SSE had no effect on cell infiltration, p16Ink4a mRNA, and DNA strand break in muscle tissues. Senescence-lowering effect of HIIE was particularly prominent in the muscle with high pre-exercise p16INK4a expression, suggesting that exercise intensity determines the level of selection pressure to tissue stem cells at late senescent stage in human skeletal muscle. This evidence provides an explanation for the discrepancy between destructive nature of high intensity exercise and its anti-aging benefits.

Pax7+ Satellite Cells in Human Skeletal Muscle After Exercise: A Systematic Review and Meta-analysis.

BACKGROUND: Skeletal muscle has extraordinary regenerative capabilities against challenge, mainly owing to its resident muscle stem cells, commonly identified by Pax7+, which expediently donate nuclei to the regenerating multinucleated myofibers. This local reserve of stem cells in damaged muscle tissues is replenished by undifferentiated bone marrow stem cells (CD34+) permeating into the surrounding vascular system. OBJECTIVE: The purpose of the study was to provide a quantitative estimate for the changes in Pax7+ muscle stem cells (satellite cells) in humans following an acute bout of exercise until 96 h, in temporal relation to circulating CD34+ bone marrow stem cells. A subgroup analysis of age was also performed. METHODS: Four databases (Web of Science, PubMed, Scopus, and BASE) were used for the literature search until February 2022. Pax7+ cells in human skeletal muscle were the primary outcome. Circulating CD34+ cells were the secondary outcome. The standardized mean difference (SMD) was calculated using a random-effects meta-analysis. Subgroup analyses were conducted to examine the influence of age, training status, type of exercise, and follow-up time after exercise. RESULTS: The final search identified 20 studies for Pax7+ cells comprising a total of 370 participants between the average age of 21 and 74 years and 26 studies for circulating CD34+ bone marrow stem cells comprising 494 participants between the average age of 21 and 67 years. Only one study assessed Pax7+ cells immediately after aerobic exercise and showed a 32% reduction in exercising muscle followed by a fast repletion to pre-exercise level within 3 h. A large effect on increasing Pax7+ cell content in skeletal muscles was observed 24 h after resistance exercise (SMD = 0.89, p < 0.001). Pax7+ cells increased to ~ 50% above pre-exercise level 24-72 h after resistance exercise. For a subgroup analysis of age, a large effect (SMD = 0.81, p < 0.001) was observed on increasing Pax7+ cells in exercised muscle among adults aged > 50 years, whereas adults at younger age presented a medium effect (SMD = 0.64, p < 0.001). Both resistance exercise and aerobic exercise showed a medium overall effect in increasing circulating CD34+ cells (SMD = 0.53, p < 0.001), which declined quickly to the pre-exercise baseline level after exercise within 6 h. CONCLUSIONS: An immediate depletion of Pax7+ cells in exercising skeletal muscle concurrent with a transient release of CD34+ cells suggest a replenishment of the local stem cell reserve from bone marrow. A protracted Pax7+ cell expansion in the muscle can be observed during 24-72 h after resistance exercise. This result provides a scientific basis for exercise recommendations on weekly cycles allowing for adequate recovery time. Exercise-induced Pax7+ cell expansion in muscle remains significant at higher age, despite a lower stem cell reserve after age 50 years. More studies are required to confirm whether Pax7+ cell increment can occur after aerobic exercise. CLINICAL TRIAL REGISTRATION: Registered at the International Prospective Register of Systematic Reviews (PROSPERO) [identification code CRD42021265457].

Fermented soybean enhances post-meal response in appetite-regulating hormones among Indonesian girls with obesity.

OBJECTIVE: To assess the post-meal response in appetite-regulating hormones acyl-ghrelin and insulin after fermented soybean (tempeh) consumption in girls with obesity. METHODS: A randomized counter-balanced crossover study was conducted using a breakfast (307 kcal, protein: 28%, fat: 23%, and carbohydrate: 55%) containing fermented soybean or isocaloric non-fermented soybean among 13 females (aged 18-20 y; BMI 25-30) after an overnight fast. The outcome variables were plasma acyl-ghrelin, insulin, arginine and score of the visual analog scale (VAS) appetite questionnaire. RESULTS: While no change was observed after the non-fermented soybean meal, plasma acyl-ghrelin decreased by 35% at 30 min and remained below baseline until 120 min after the fermented soybean meal (P < 0.05). Plasma insulin increased after consumption of both meals and fermented soybean meal-induced 30% greater response in insulin at 120 min than non-fermented soybean meal (P < 0.05). Circulating arginine levels were slightly greater (24%) at 120 min after the fermented soybean meal than the non-fermented soybean meal (P < 0.05). No difference in subjective appetite was observed between the fermented soybean meal and the non-fermented soybean meal. CONCLUSIONS: Fermented soybean meal induced greater response in appetite-regulating hormones compared with non-fermented soybean meal. No difference in post-meal satiety feeling between fermented and non-fermented soybean meal suggests poor sensitivity of the brain to the appetite-regulating hormones among girls with obesity.

The Prospect for Type 2 Diabetes Mellitus Combined with Exercise and Synbiotics: A Perspective.

Change in gut microbiome diversity (the so-called dysbiosis) is correlated with insulin resistance conditions. Exercise is typically the first management for people with type 2 diabetes mellitus (T2DM), which is generally well-known for improving glucose regulation. The new prebiotics and probiotics, like synbiotics, designed to target specific diseases, require additional studies. While the effectiveness of exercise combined with synbiotics seems promising, this review discusses these agents' possibility of increasing the gut microbiota's diversity. Therefore, they could enhance short-chain fatty acids (SCFA). In particular, the synbiotic interaction on gut microbiota, the exercise mechanism in improving gut microbiota, and the prospect of the synergistic effect of the combination of synbiotic and exercise to improve insulin sensitivity are addressed.

The Impact of Weight Loss Program in Metabolic Profile and Body Fat Improvement among Indonesian Young Obese: A Randomized Clinical Trial.

Abdominal obesity is defined as an accumulation visceral fat in abdomen region. It is linked to metabolic disorders that contribute to chronic diseases. Triglyceride (TG) to high-density lipoprotein (TG/HDL) ratio is considered as an insulin resistance (IR) marker. The waist to height ratio (WHtR) has been advocated as an effective and convenient measurement of central adiposity that could potentially be superior instead of BMI in determining cardiometabolic risk. The objective of this study was to investigate the effect of 8-wk-high protein diet and exercise on TG/HDL ratio, waist to height ratio (WHtR), body fat (BF) and body weight (BW). This study was a randomized clinical trial in 43 subjects with BMI >25 kg/m2. Subjects were randomized into 3 groups: High Protein Diet and Exercise (HPDE; n=15) High Protein Diet (HPD; n=15) and Control Group (CG; n=13). The prescribed diet consisted of 1,200 calories; while the exercise was conducted for 5 times/wk for 8 wk. The hypocaloric diet comprised of 55% carbohydrate, 25% protein, and 20% fat. In the end of the study, HPDE group had greater weight loss (-2.3±1.9 kg) than HPD (-1.8±2.2 kg); while CG increased in weight (1.8±1.3 kg). HPDE group had significantly improved TG, HDL, TG/HDL ratio and WHtR by -26.6 mg/dL, 12.7 mg/dL, -1.02, -0.02 respectively (p<0.05). There were significant differences between 3 groups, with ΔTG (p=0.008), ΔHDL (p=0.001), and ΔTG/HDL ratio (p=0.004) and WHtR (p=0.001). In conclusion, t hypocaloric diet combined with exercise has a beneficial effect in weight loss among young obese.