Regular endurance exercise of overloaded muscle of young and old male mice does not attenuate hypertrophy and improves fatigue resistance

It has been observed that there is an inverse relationship between fiber size and oxidative capacity due to oxygen, ADP, and ATP diffusion limitations. We aimed to see if regular endurance exercise alongside a hypertrophic stimulus would lead to compromised adaptations to both, particularly in older animals. Here we investigated the effects of combining overload with regular endurance exercise in young (12 months) and old (26 months) male mice. The plantaris muscles of these mice were overloaded through denervation of synergists to induce hypertrophy and the mice ran on a treadmill for 30 min per day for 6 weeks. The hypertrophic response to overload was not blunted by endurance exercise, and the increase in fatigue resistance with endurance exercise was not reduced by overload. Old mice demonstrated less hypertrophy than young mice, which was associated with impaired angiogenesis and a reduction in specific tension. The data of this study suggest that combining endurance exercise and overload induces the benefits of both types of exercise without compromising adaptations to either. Additionally, the attenuated hypertrophic response to overload in old animals may be due to a diminished capacity for capillary growth

Endurance exercise plus overload induces fatigue resistance and similar hypertrophy in mice irrespective of muscle mass.

NEW FINDINGS:What is the central question of this study? Does combining endurance and hypertrophic stimuli blunt the adaptations to both modalities and is this effect greater in muscles with larger baseline fibre cross sectional area? What is the main finding and its importance? Endurance exercise and hypertrophic stimuli can be combined to increase fatigue resistance and fibre size without blunting either adaptation regardless of baseline fibre size. ABSTRACT:Previous studies have demonstrated that fibre cross-sectional area (FCSA) is inversely related to oxidative capacity, which is thought to be determined by diffusion limitations of oxygen, ADP and ATP. Consequently, it is hypothesised that (1) when endurance training is combined with a hypertrophic stimulus the response to each will be blunted, and (2) muscles with a smaller FCSA will show a larger hypertrophic response than those with a large FCSA. To investigate this, we combined overload with endurance exercise in 12-month-old male mice from three different strains with different FCSA: Berlin High (BEH) (large fibres), C57BL/6J (C57) (normal-sized fibres) and Berlin Low (BEL) (small fibres). The right plantaris muscle was subjected to overload through denervation of synergists with the left muscle acting as an internal control. Half the animals trained 30 min per day for 6 weeks. The overload-induced hypertrophy was not blunted by endurance exercise, and the exercise-induced increase in fatigue resistance was not impaired by overload. All strains demonstrated similar absolute increases in FCSA, although the BEH mice with more fibres than the C57 mice demonstrated the largest increase in muscle mass and BEL mice with fewer fibres the smallest increase in muscle mass. This study suggests that endurance exercise and hypertrophic stimuli can be combined without attenuating adaptations to either modality, and that increases in FCSA are independent of baseline fibre size

Identification and comparison of m6A modifications in glioblastoma non-coding RNAs with MeRIP-seq and Nanopore dRNA-seq

The most prominent RNA modification – N6-methyladenosine (m6A) – affects gene regulation and cancer progression. The extent and effect of m6A on long non-coding RNAs (lncRNAs) is, however, still not clear. The most established method for m6A detection is methylated RNA immunoprecipitation and sequencing (MeRIP-seq). However, Oxford Nanopore Technologies recently developed direct RNA-seq (dRNA-seq) method, allowing m6A identification at higher resolution and in its native form. We performed whole transcriptome sequencing of the glioblastoma cell line U87-MG with both MeRIP-seq and dRNA-seq. For MeRIP-seq, m6A peaks were identified using nf-core/chipseq, and for dRNA-seq – EpiNano pipeline. MeRIP-seq analysis revealed 5086 lncRNAs transcripts, while dRNA-seq identified 336 lncRNAs transcripts from which 556 and 198 were found to be m6A modified, respectively. While 24 lncRNAs with m6A overlapped between two methods. Gliovis database analysis revealed that the expression of the major part of identified overlapping lncRNAs was associated with glioma grade or patient survival prognosis. We found that the frequency of m6A occurrence in lncRNAs varied more than 9-fold throughout the provided list of 24 modified lncRNAs. The highest m6A frequency was detected in MIR1915HG, THAP9-AS1, MALAT1, NORAD1, and NEAT1 (49–88nt), while MIR99AHG, SNHG3, LOXL1-AS1, ILF3-DT showed the lowest m6A frequency (445–261nt). Taken together, (1) we provide a high accuracy list of 24 m6A modified lncRNAs of U87-MG cells; (2) we conclude that MeRIP-seq is more suitable for an initial m6A screening study, due to its higher lncRNA coverage, whereas dRNA-seq is most useful when more in-depth analysis of m6A quantity and precise location is of interest. Abbreviations: (dRNA-seq) direct RNA-seq, (GBM) glioblastoma, (LGG) low-grade glioma, (lncRNAs) long non-coding RNAs, (m6A) N6-methyladenosine, (MeRIP-seq) methylated RNA immunoprecipitation and sequencing, (ncRNA) non-coding RNA, (ONT) Oxford Nanopore Technologi; Lietuvos Mokslo Taryba</p

Response to three weeks of sprint interval training cannot be explained by the exertional level

Background and Objectives: The all-out mode of sprint interval training (SIT) has been shown to be an efficient method for improving sports performance, exercise capacity, and aerobic fitness. Although the benefits of SIT are well described, the mechanisms underlying the different degrees of response remain largely unexplored. We aimed to assess the effects of exertion on the responsiveness to SIT. Materials and Methods: The participants were 28 young untrained men (mean ± SD age 25.7 ± 6.03 years) who exhibited either a large or small increase in Wingate test average power in response to nine SIT sessions performed over three weeks. Each training session comprised four-six bouts of 30 s all-out cycling interspaced with 4 min of rest. Individual responses were assessed using heart rate (HR) during exercise for all nine sessions, as well as blood lactate concentration up to 1 h, and the decrement in maximal voluntary knee extension torque (MVC) up to 24 h after the first and last training sessions. Peak oxygen uptake (VO2peak) and maximum HR were measured before and after training during an incremental cycling test to exhaustion. Results: Although all participants showed benefits of SIT such as increased VO2peak, the increase in anaerobic cycling power varied between participants. We identified 17 high responders and nine low responders, whose average power outputs were 0.80 ± 0.22 and 0.22 ± 0.19 W/kg, respectively. The HR achieved during any of the training sessions did not differ between high and low responders. The lactate kinetics did not differ between groups before and after the intervention. Training resulted in a more rapid recovery of MVC without any discernible differences between the high and low responders. Conclusion: The differences in the responses to SIT are not dependent on the exertion level during training

Very low volume high-intensity interval exercise is more effective in young than old women

We investigated the acute neuromuscular and stress responses to three different high-intensity interval training sessions in young (age 19.5 +/- 1.3 years) and older (age 65.7 +/- 2.8 years) women. Cycling exercise comprised either 6 x 5 s or 3 x 30 s all-out, or 3 x 60 s submaximal, efforts each performed 5 weeks apart in randomized order. Peak and average power was higher in young than in older women and was largest during the 6 x 5 s strategy in both groups (p < 0.05). The decrease in the ratio of torques evoked by 20 and 100 Hz electrical stimulation, representing low-frequency fatigue, was more evident after the 3 x 30 and 3 x 60 s than the 6 x 5 s bout in both groups and was larger in young than in older women (p < 0.05). Both groups preferred 6 x 5 s cycling for further training. In conclusion, in young women, very low volume (6 x 5 s) all-out exercise induces significant physiological stress and seems to be an effective means of training. For older women, longer exercise sessions (3 x 60 s) are more stressful than shorter ones but are still tolerable psychologically

Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice

Selenium is an essential trace element that maintains normal brain function, mainly due its antioxidant properties. Although the amount of Se in the body is tightly regulated by the liver, both an excess of and deficiency in Se can modulate the cellular redox status and affect the homeostasis of other essential elements for both humans and animals. The aim of this study was to determine the effect of inorganic selenium excess on oxidative stress and iron homeostasis in brain and liver of laboratory BALB/c mice, which were supplemented with Na2SeO3 solution (0.2 mg and 0.4 mg Se/kg body weight) for 8 weeks. The content of the lipid peroxidation product malondialdehyde and antioxidant enzyme catalase activity/gene expression were used as markers of oxidative damage and were evaluated by spectrophotometric assays. Selenium and iron concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). Catalase gene expression was analyzed by qRT-PCR and &Delta;&Delta;Ct methods. Our results showed that doses of 0.2 mg Se and 0.4 mg Se caused a relatively low accumulation of Se in the brain of mice; however, it induced a 10-fold increase in its accumulation in the liver and also increased iron accumulation in both tested organs. Both doses of Se increased the content of malondialdehyde as well as decreased catalase activity in the liver, while the 0.4 mg Se dose has also activated catalase gene expression. Brain of mice exposed to 0.2 mg Se showed reduced lipid peroxidation; however, the exposure to 0.4 mg of Se increased the catalase activity as well as gene expression. One may conclude that exposure to both doses of Se caused the accumulation of this micronutrient in mice brain and liver and have also provided a disrupting effect on the levels of iron. Both doses of Se have triggered oxidative liver damage. In the brain, the effect of Se was dose dependent, where &minus;0.2 mg of Se provided antioxidant activity, which was observed through a decrease in lipid peroxidation. On the contrary, the 0.4 mg dose increased brain catalase activity as well as gene expression, which may have contributed to maintaining brain lipid peroxidation at the control level