Redox regulation is a fundamental physiological phenomenon related to oxygen-dependent metabolism, and skeletal muscle is mainly regarded as a primary site for oxidative phosphorylation. Several studies have revealed the importance of reactive oxygen and nitrogen species (RONS) in the signaling process relating to muscle adaptation during exercise. To date, improving knowledge of redox signaling in modulating exercise adaptation has been the subject of comprehensive work and scientific inquiry. The primary aim of this review is to elucidate the molecular and biochemical pathways aligned to RONS as activators of skeletal muscle adaptation and to further identify the interconnecting mechanisms controlling redox balance. We also discuss the RONS-mediated pathways during the muscle adaptive process, including mitochondrial biogenesis, muscle remodeling, vascular angiogenesis, neuron regeneration, and the role of exogenous antioxidants.

Exercise-induced reactive oxygen and nitrogen species are increasingly considered as beneficial health promotion. Astaxanthin (ASX) has been recognized as a potent antioxidant suitable for human ingestion. We investigated whether ASX administration suppressed antioxidant enzyme activity in moderate-intensity exercise. Seven-week-old male C57BL/6 mice (n = 8/group) were treated with ASX (5, 15, and 30 mg/kg BW) combined with 45 min/day moderate-intensity swimming training for four weeks. Results showed that the mice administrated with 15 and 30 mg/kg of ASX decreased glutathione peroxidase, catalase, malondialdehyde, and creatine kinase levels in plasma or muscle, compared with the swimming control group. Beyond that, these two (15 and 30 mg/kg BW) dosages of ASX downregulated gastrocnemius muscle erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Meanwhile, mRNA of Nrf2 and Nrf2-dependent enzymes in mice heart were also downregulated in the ASX-treated groups. However, the mice treated with 15 or 30 mg/kg ASX had increased constitutive nitric oxidase synthase and superoxide dismutase activity, compared with the swimming and sedentary control groups. Our findings indicate that high-dose administration of astaxanthin can blunt antioxidant enzyme activity and downregulate transcription of Nrf2 and Nrf2-dependent enzymes along with attenuating plasma and muscle MDA.

Background: Alzheimer’s disease (AD) is a progressive disorder characterized by cognitive decline. Physical exercise and audiovisual stimulation have gained increasing concern for their potential to mitigate AD pathology. However, the therapeutic advantages of combining these interventions and the precise molecular mechanisms underlying these strategies need further demonstration. Objectives: This study aimed to assess the protective effects and underlying mechanisms of physical exercise combined with audiovisual stimulation on cognitive and affective functions, as well as on pathological alterations in AD mice. Methods: Both AD model mice established by injecting Aβ₄₂ oligomers into hippocampus and APP/PS1 AD transgenic mice were used. Mice were subjected to treadmill training, 40 Hz audio-visual stimulation, or a combination of these interventions, respectively. After the interventions, the cognitive and anxiety/depression-like behaviors were evaluated by novel object recognition, morris water maze, open field, tail suspension, or forced swimming, respectively. Quantitative proteomics combined with molecular analyses and transmission electron microscopy were used to systematically evaluate the underlying mechanism of multimodal interventions in AD model mice. Results: The multimodal intervention significantly prevented cognitive impairment and ameliorated anxiety/depression-like behaviors of APP/PS1 AD transgenic mice and AD model mice induced by injecting Aβ₄₂ oligomers, outperforming single-modality treatments. It markedly diminished hippocampal accumulation of β-amyloid (Aβ) and tau phosphorylation in AD mice. Multiple interventions also reversed synapse loss of AD mice. Proteomic analyses revealed that multimodal intervention exerted a more comprehensive restoration of dysregulated proteins in AD mice compared to single-modality interventions. The interventions have synergetic effects in decreasing inflammation reactions and restoring the autophagy-lysosomal function. Multimodal intervention upregulated the expression TFEB, and concurrently increased HSPA1L expression to restore lysosomal membrane integrity. The degradation function of lysosomes was also improved by multimodal intervention as revealed by the decreased LC3II/I ratio, reduced p62 level, as well as alleviated lysosome enlargement in AD mice. Upregulation of HSPA1L reversed the disruption of lysosome membrane integrity of AD transegenic mice, thereby reversed the increased accumulation of Aβ and cognitive defects of AD. Conclusion: Physical exercise and audiovisual stimulation exert synergistic effects in decreasing the inflammation reaction and maintaining autophagy-lysosomal homeostasis by increasing the biogenesis of lysosomes and restoring the integrity of lysosome membrane, thereby reducing Aβ deposition and cognitive defect of AD mice. This study highlights the significant therapeutic potential of multimodal, non-pharmacological strategies for Alzheimer’s disease.