Search Results (796)

Hydrogel-based stem cell therapy uses different stem cells and bioactive molecules for wound healing in the treatment of diabetes and chronic burn wounds by accelerating angiogenesis, collagen deposition, and inhibition of inflammatory responses. Artificial vessels have already been used for patients with cardiovascular diseases, but most of them are polymeric, which can cause thrombosis and restenosis. 3D bioprinting combines cells, growth factors, and biomaterials to create a setting in which cells grow and differentiate into native tissue-like structures. The current study aimed to create a model of blood vessels using collagen and hyaluronic acid hydrogel combined with endothelial and muscle progenitor cells derived from amniotic mesenchymal stem cells using 3D bioprinting. A computer-aided design (CAD) software was employed to create the 3D models of a blood vessel model and printed using a 3D bioprinter with two printheads: one with bioink encapsulating endothelial progenitor cells and the second with bioink encapsulating smooth muscle progenitor cells. The blood vessel constructs were characterized morphologically and structurally by Fourier Transform Infrared (FTIR) Spectroscopy, thermogravimetric analysis (TGA), Scanning Electron Microscopy (SEM), immunohistochemistry, water uptake, and enzymatic degradation. Viability, proliferation, oxidative stress, vascular endothelial growth factor (VEGF) and nitric oxide (NO) production were assessed to demonstrate the cytocompatibility of the blood vessel constructs. Our results showed that collagen–hyaluronic acid hydrogels embedded with stem cells can be used for vascular constructs, meeting the desired requirements of biocompatibility and accuracy in reproducing the model created in the CAD software v1.0. Full article

The global seafood industry faces persistent challenges related to product quality, safety, and authenticity, driven by complex supply chains, increasing demand, and the perishable nature of aquatic products. Traditional analytical methods often fall short in providing rapid, comprehensive, and non-destructive insights into the intricate biochemical changes occurring in seafood. ¹H Nuclear Magnetic Resonance (¹H NMR) spectroscopy has emerged as a powerful and versatile tool for metabolomics, offering a holistic view of the low-molecular-mass compounds (metabolites) present in biological samples. The present study applied ¹H NMR for chemical fingerprint identification in mullets (Mugil liza) from Brazil. Dorsal muscle samples were taken from the fish during summer, autumn, and winter. The procedure involved freeze-drying the muscle tissue, thereafter extracting polar metabolites using designated solvents (methanol, water, and chloroform), and analyzing them using a 600 MHz spectrometer. As a result, 23 metabolites related to degradation biomarkers, essential metabolites, energy expenditure, and muscle structure were identified. The statistical analysis demonstrated a distinct separation between the geographical origins (RJ vs. SC), mostly influenced by variations in the concentrations of lactate, histidine, threonine, phenylalanine, and ornithine. Factors like fish size and seasonal variations did not markedly affect the overall metabolic profile, underscoring the reliability of these chemicals as stable origin indicators. The Principal Component Analysis identified two distinct groups of metabolites, establishing a profile for each geographical origin. The developed protocol can be applied to the processes of geographical identification. Thus, the ¹H NMR tool was efficient in determining metabolites that can be considered biomarkers in analyses for seafood traceability. Full article

Background/Objectives: Cancer cachexia (CC) is a metabolic syndrome characterized by the progressive loss of skeletal muscle and adipose tissue during tumor progression. Despite its clinical prevalence, effective therapeutic options are currently lacking. Phloretin, a natural flavonoid with potent anti-inflammatory and antioxidant properties, has unclear efficacy against CC. This study investigates the therapeutic potential of phloretin in ameliorating cancer cachexia. Methods: Mouse models of CC were established using BALB/c mice implanted with C26 colon carcinoma cells and C57BL/6 mice implanted with Lewis lung carcinoma (LLC) cells. Upon the detection of palpable tumors, phloretin (10 mg/kg) was administered daily via intraperitoneal injection. At the endpoint, hind limb skeletal muscle, inguinal white adipose tissue (iWAT), and hearts were harvested and weighed. Lean body mass was assessed by analyzing the weight of the carcass following the excision of skin, subcutaneous fat, and visceral organs. Gene expression and protein levels in muscle tissues were subsequently quantified. Results: Phloretin administration significantly alleviated tumor-induced loss of tumor-free body weight. It effectively preserved skeletal muscle mass in both C26 and LLC cachexia models, while significantly attenuating adipose tissue depletion in the C26 model. In vitro, phloretin treatment mitigated myotube atrophy induced by C26 conditioned medium. Mechanistically, phloretin inhibited STAT3 activation in skeletal muscle. This inhibition suppressed the expression of the E3 ubiquitin ligases MuRF-1 and Atrogin-1. Furthermore, phloretin concurrently modulated the autophagy pathway. Conclusions: Phloretin effectively ameliorates cancer cachexia-induced muscle wasting by targeting STAT3-mediated protein degradation and autophagy pathways. These findings suggest that phloretin represents a promising therapeutic agent for the clinical management of cancer-associated cachexia. Full article

This study evaluated the effects of dietary supplementation with goji berries (Lycium barbarum) on the nutritional profile, oxidative stability, and shelf life of rabbit meat. Thirty-two rabbits were assigned to two dietary treatments: a control diet (CN) and the same diet supplemented with 3% dried goji berries (GJ). Proximate composition and fatty acid profile of the Longissimus thoracis et lumborum muscle were determined at dissection, whereas physical, microbiological, and biochemical parameters were evaluated during refrigerated storage (4 °C; 1, 4, and 10 days) and frozen storage (−20 °C; 60 and 120 days). Dietary supplementation significantly modified the lipid profile of the meat, reducing saturated fatty acids and increasing long-chain n-3 and n-6 polyunsaturated fatty acids. During refrigerated storage, lipid peroxidation increased in both groups; however, meat from the GJ group showed significantly lower TBARS values after 10 days (0.22 vs. 0.33 mg MDA/kg; p < 0.001), indicating improved oxidative stability. Lower accumulation of total volatile basic nitrogen (TVB-N), reduced formation of biogenic amines, and slower growth of spoilage-related microbial populations, particularly Pseudomonas spp., were also observed in GJ samples. Overall, the GJ diet improved fatty acid composition and delayed degradative processes during storage, suggesting its potential as a functional feed ingredient to enhance rabbit meat quality and shelf life. Full article

Conventional gel electrodes are the gold standard for surface electromyography (sEMG), yet their bulkiness, stiffness, and limited gel lifetime prevents seamless day-long integration with wearable robots. We integrated ultrathin skin-conformal temporary tattoo electrodes with a powered unilateral hip exoskeleton and compared signal quality during treadmill walking against gel. In this pilot study, five healthy participants completed three consecutive walking blocks at fixed speed: (1) using gel electrodes; (2) using tattoo electrodes to compare signal quality; and (3) using the same tattoo electrodes (not repositioned) after eight hours of wear to simulate a full day of typical device use and to evaluate potential degradation in signal quality over time. Electrodes were positioned on muscles not covered by the exoskeleton interface (tibialis anterior and gastrocnemius medialis), as well as on muscles located beneath the exoskeleton cuff, which were potentially subject to motion artifacts due to the application of external forces by the exoskeleton (rectus femoris and biceps femoris, BF). Across all muscles, for both gel and tattoo electrodes, the root mean square error (RMSE) between normalized sEMG envelopes and biological activation profile was 0.069 ± 0.048, and Pearson’s correlation coefficient (ρ) was 0.844 ± 0.091. Re-testing the same tattoo electrode pair after eight hours confirmed day-long stability without the need for recalibration. Statistical analysis revealed no significant differences in signal quality, also when applying assistive forces, between the two electrode types and across all muscles (RMSE, all p ≥ 0.3125; ρ, all p ≥ 0.1250), as well as no degradation after eight hours (RMSE and ρ: all p ≥ 0.0626, uncorrected). Finally, in a proof-of-concept session, BF activity measured with tattoo electrodes was found reliable to drive hip-extension assistance in real time. Collectively, these results show that tattoo electrodes deliver signal quality comparable to gel electrodes while offering a low-profile skin-conformal interface and day-long usability, making them a promising option for enhancing EMG-based control in wearable robots. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Background: Chronic kidney disease (CKD) associated vascular calcification (VC) is a leading cause of cardiovascular mortality, partially driven by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation cellular process. However, the precise role and mechanism of CMA in CKD-associated vascular calcification remain unknown. Methods: We studied calcified arteries from CKD patients and rats fed on a high-phosphate diet using histological and ultrastructural methods. VSMCs’ calcification was induced by a calcification medium containing high phosphate and calcium. CMA activity was measured by a KFERQ reporter and lysosomal staining. The expression of LAMP2a and HSP90AA1 was knocked down by siRNA, overexpressed by plasmid, and activated by QX77.1. Bioinformatic analysis, protein interaction studies, immunofluorescence and co-immunoprecipitation were performed to investigate the potential mechanism of CMA in VC. Results: The expression of LAMP2a was increased in human calcified radial artery tissues (n = 3, p < 0.05) and rats’ calcified aortic tissues (n = 3, p < 0.01), accompanied by lysosomal abnormalities. The activity of CMA was increased during the osteogenic transdifferentiation of VSMCs, as indicated by increased expression of RUNX2 and reduced expression of SM22α (p < 0.05). LAMP2a knockdown attenuated VSMCs’ calcification (p < 0.05), whereas pharmacological activation of CMA aggravated calcification in VSMCs (p < 0.01). Bioinformatic screening identified HSP90AA1 as a candidate involved in CMA in vascular calcification. Elevated HSP90AA1 expression was observed in human calcified radial artery tissues (n = 3, p < 0.01) and rat calcified aortic tissues (n = 3, p < 0.01), which promoted osteogenic transdifferentiation of VSMCs (p < 0.05). HSP90AA1 interacted with LAMP2a and positively regulated its expression (p < 0.01). Conclusions: These findings support an association between CMA activation and CKD vascular calcification. It suggests that HSP90AA1 facilitates vascular calcification in chronic kidney disease involving chaperone-mediated autophagy. Full article

The large yellow croaker (Larimichthys crocea) is a high-value marine fish, but stress during live transport often leads to physiological disturbance and deterioration of muscle quality. This study investigated the effects of pre-transport temporary rearing at three temperatures (8, 10, and 12 °C) over 48 h on stress response, energy allocation, and muscle quality in this fish species. Temporary rearing at 8 °C induced stronger cold stress, characterised by elevated cortisol, marked lipid mobilisation, late lactate rebound, and greater loss of polyunsaturated fatty acids, indicating enhanced stress–catabolism coupling and higher risk of quality deterioration. In contrast, 12 °C did not sufficiently suppress metabolic turnover, resulting in continuous glycogen depletion, rapid ATP degradation, and accelerated accumulation of bitter-tasting nucleotide metabolites such as hypoxanthine. Among the tested temperatures, 10 °C showed the most coordinated response, with relatively stable endocrine status, moderate substrate utilisation, lower accumulation of undesirable degradation products, and better preservation of texture, water-holding capacity, and flavour-related precursors. These findings suggest that 10 °C is a promising pre-transport temporary rearing temperature for large yellow croakers under the present 48 h experimental conditions. The advantage of this temperature appears to lie in achieving a more favourable balance between metabolic suppression and physiological homeostasis, thereby providing a scientific basis for improving pre-transport rearing management and supporting safer, more stable live transport. Future studies incorporating behavioural and molecular indicators are needed to further clarify the regulatory effects of 10 °C during pre-transport rearing. Full article

Meat quality serves as a pivotal determinant of consumer purchasing behavior and of the economic viability of the livestock industry; as such, research into its regulatory mechanisms is of critical significance for the development of modern agriculture. Traditional investigations into meat quality have predominantly centered on sensory and physicochemical assessments of ultimate phenotypic traits, thereby facing inherent limitations in systematically deciphering the intricate molecular regulatory networks underlying meat quality formation. By contrast, an integrated analysis of the transcriptome and metabolome effectively connects the cascade of “gene transcription—metabolic regulation—phenotypic determination,” which has emerged as a core methodological paradigm in contemporary research on the molecular mechanisms governing meat quality. This review systematically delineates the evolutionary trajectory and principal technological frameworks of meat quality evaluation systems, with a focused synthesis of recent advances achieved through combined transcriptomic and metabolomic analyses in the field of meat quality regulation. The scope of this review encompasses core transcriptional regulatory networks associated with meat quality attributes, pivotal metabolic pathways, signal transduction mechanisms, and protein degradation dynamics. Furthermore, the regulatory impacts exerted by genetic variation among breeds, nutritional modulation, rearing environments, and stress responses on meat quality characteristics are comprehensively elucidated. Integrative analysis reveals that combined transcriptome–metabolome approaches transcend the inherent limitations of single-omics investigations, systematically unraveling the hierarchical regulatory mechanisms governing fundamental meat quality traits, such as muscle fiber type differentiation, postmortem glycolytic progression, intramuscular fat deposition, and flavor compound accumulation. Such integrative strategies have facilitated the identification of functional genes and metabolic biomarkers with potential utility for the early prediction of meat quality outcomes. Concurrently, this review acknowledges persistent challenges confronting the field, including the absence of standardized protocols for multi-omics data integration, insufficient functional causal validation, and a discernible disconnect between research discoveries and practical industrial implementation. Building upon this comprehensive assessment, prospective directions for future multi-omics research in meat quality are proposed, accompanied by the formulation of an integrated end-to-end improvement framework spanning fundamental research, technological innovation, and industrial application. Collectively, this review provides a systematic theoretical foundation for the in-depth elucidation of mechanisms that determine meat quality and the precision-oriented regulation of quality-determining traits in livestock production practices, thereby offering substantial scientific guidance for quality improvement initiatives within the animal husbandry sector. Full article

This study evaluated the efficacy of ammonia-nitrogen-reducing biofilms (aquatic nitrifying bacteria biofilm media, a fixed-bed biofilm capable of simultaneous nitrification and denitrification) in mitigating water quality deterioration and transport-induced physiological stress in live-transported Crucian carp (Carassius auratus). In a simulated bag transport system, the application of the biofilm significantly decreased ammonia-nitrogen concentrations through enhanced nitrification, stabilized pH and dissolved oxygen dynamics, and suppressed nitrite accumulation. Correspondingly, biofilm-treated fish exhibited significantly reduced systemic stress responses, as evidenced by reduced serum cortisol, glucose, and lactate dehydrogenase concentrations, along with diminished histopathological changes in gill and liver tissues and preserved muscle fiber integrity. Regarding post-transport muscle quality, biofilm treatment delayed glycogen catabolism and lactate accumulation, maintained elevated muscle pH and water-holding capacity, reduced shear force decline, decelerated ATP hydrolysis and freshness degradation (K-value), and simultaneously suppressed lipid peroxidation and myonuclear apoptosis. These findings demonstrate that ammonia-nitrogen-reducing biofilms represent a viable biotechnological approach for maintaining water quality, mitigating stress-induced physiological disturbances, and preserving flesh quality during live fish transportation. This approach has significant potential for improving post-harvest outcomes in aquaculture logistics. Full article

Background: Muscle atrophy is a major feature of Limb Girdle Muscular Dystrophy R1 (LGMDR1) patients, but its underlying molecular mechanisms have not been fully explored. While the ubiquitin–proteasome system (UPS) is known to be involved in muscle protein degradation, inflammation commonly observed in LGMDR1 patients may further activate the UPS. This study aimed to explore the role of inflammation in the muscle atrophy of LGMDR1 patients. Methods: Muscle biopsies from six confirmed LGMDR1 patients (with CAPN3 variants and reduced calpain-3 protein expression) were analyzed for atrophy-related markers, MuRF1 and Atrogin-1, using qRT-PCR and Western blotting. The expression of cytokines, TNF-α, IL-1β, and IL-6 was analyzed by qRT-PCR from muscle biopsies and by ELISA from serum samples. The NFκB, FOXO1, and FOXO3 gene expression was analyzed using qRT-PCR and Western blotting from muscle biopsies. Results: Elevated TNF-α levels were associated with increased UPS activity, reflected by upregulated NFκB, FOXO1, MuRF1, and Atrogin-1 expression in LGMDR1. Conclusion: Our findings indicate that increased TNF-α expression is associated with muscle wasting in LGMDR1 patients by targeting UPS pathway mediators that activate ubiquitin ligases—MuRF1 and Atrogin-1. These findings suggest that targeting TNF-α signaling and its downstream factors may help develop therapeutic interventions to prevent muscle atrophy in LGMDR1 patients. Full article

Introduction: Intracranial aneurysms (IAs) are focal dilatations of cerebral arteries that carry a significant risk of rupture and subarachnoid hemorrhage (aSAH). Advances in basic science have improved understanding of vascular wall biology, hemodynamic stress, inflammation, and genetic contribution to aneurysm rupture. Rapid progress in neurovascular therapeutics highlights the need to evaluate emerging molecular and pharmacologic strategies targeting IAs. Methodology: This narrative review synthesizes evidence from 2015 to 2025 on the cellular, molecular, and biomechanical mechanisms underlying IA pathophysiology. A structured search of PubMed, Scopus, and Embase identified studies examining molecular pathways, genetic determinants, and therapeutic approaches. Discussion: Aneurysm initiation involves endothelial responses to abnormal shear stress, activating NF-κB, MAPK, and calcium-dependent pathways that promote inflammation, smooth-muscle cell apoptosis, and extracellular matrix degradation. Pharmacologic candidates including MCP-1 antagonists, PPARγ agonists, and IL-6/STAT3 inhibitors reduce inflammatory remodeling, while doxycycline and cathepsin inhibitors preserve matrix integrity. Emerging strategies like microRNA modulation, tyrosine-kinase inhibition, and gene-based delivery offer potential for localized, durable stabilization with minimal systemic toxicity. Conclusions: Integrating surgical and biologic therapies may shift IA management from reactive repair to rupture prevention. Full article

Background: Main risk factors associated with the development of sarcopenia (coexistence of muscle mass loss and dysfunction) are a sedentary lifestyle coupled with obesity. Associated mitochondrial dysfunction leads to energy deficits and perturbations in the balance between protein synthesis and degradation, thereby triggering muscle dysfunction or atrophy. Aside from exercise, which is challenging to implement and maintain, particularly in women, treatments for diminishing sarcopenia are scarce. The objective of the present study was to evaluate the effect of the flavanol (−)-epicatechin (EC) in a hypercaloric diet-induced obese female rat model. Muscle strength and endurance, as well as relative mitochondrial DNA content in skeletal muscle, were assessed. Methods: Female rats were fed a hypercaloric diet to induce obesity, as evidenced by increases in body weight, Lee index, and lipid profile alterations, and by abdominal fat accumulation, and to promote a sarcopenic phenotype. Functional tests of grip strength and mobility (treadmill) were performed. Mitochondrial relative content was evaluated by measuring the ratio of mtDNA/nuclear DNA, and the expression of genes related to mitochondrial biogenesis (Pgc1-α, Tfam), fusion (Mfn1 and Opa1), fission (Drp1 and Fis1), and mitophagy (Pink1 and Pkn), and function; citrate synthase and Ucp3 were also evaluated. Results: A significant decrease in mobility and strength was observed in obese female rats, accompanied by reduced mitochondrial numbers, activity, and dynamics, but not by changes in muscle size or weight. Treatment with EC induced mitochondrial biogenesis and positive changes in mitochondrial dynamics (fission and fusion) and activity, as measured indirectly by changes in citrate synthase and Ucp3 expression. Discussion: Results reinforce the potential of EC as a modulator of mitochondrial function in dysfunctional conditions associated with obesity, thereby attenuating the mechanisms underlying sarcopenia. Full article

Population aging and widespread sedentary lifestyles have increased the prevalence of chronic non-communicable diseases, many of which are linked to progressive disruptions of cellular homeostasis. Autophagy, a conserved cellular degradation and recycling pathway, plays a central role in maintaining metabolic flexibility, proteostasis, and organ function. However, aging and physical inactivity impair autophagic regulation, thereby contributing to the development of sarcopenia, cardiovascular diseases, metabolic disorders, and neurodegenerative diseases. Physical exercise is a non-pharmacological intervention that can restore autophagic activity and confer systemic health benefits in multiple preclinical and clinical contexts. Increasing evidence indicates that these benefits are mediated not only by local tissue adaptations but also by complex inter-organ communication. Central to this process are exercise-induced bioactive factors, collectively termed exerkines, including myokines, cardiokines, adipokines, hepatokines, osteokines, and circulating miRNAs. Rather than acting independently, exerkines form an integrated signaling network that fine-tunes autophagic flux across multiple tissues. Exerkine-mediated regulation of autophagy involves key pathways such as AMPK/mTOR, FoxO, SIRT1, ULK1, and TFEB, thereby coordinating energy metabolism, mitochondrial quality control, inflammation, and protein turnover in skeletal muscle, heart, liver, adipose tissue, bone, and the central nervous system. This review summarizes current evidence on representative exerkines and their roles in autophagy-dependent inter-organ crosstalk, highlighting the exercise–exerkine–autophagy axis as a promising target for preventing and managing chronic diseases. Full article

Background: During aging, skeletal muscle mass constantly diminishes and myogenic potential declines. At the cellular level, a decline in mitochondrial function is a hallmark of the aging process and the deficiency of the mitochondrial network contributes to a progressive reduction in muscle mass. Autophagic clearance of mitochondria through the process of mitophagy is required to remove impaired or damaged mitochondria, while mitophagy is a key regulator of muscle maintenance. Dysfunctional degradation of mitochondria is increasingly associated with aging (mitophaging), while mechanical stimuli have been shown to ameliorate the aging-induced impaired muscle mass and function; however, less is known about the potential effects of mechanical loading on mitophaging. The aim of the present study was to investigate the effect of mechanical stretching on mitophagy in aged myoblasts, in vitro. Methods: Cell senescence was replicated using a multiple cell division model of C2C12 myoblasts. The control and aged cells were cultured on elastic membranes and underwent passive stretching using a mechanical loading protocol of 15% elongation for 12 h at a frequency of 1 Hz. Cell signaling and gene expression responses of mitophagy-associated and myogenic regulatory factors (MRFs) were assessed through immunoblotting and qRT-PCR of the cell lysates derived from stretched and non-stretched control and aged myoblasts. Results: Mitophagy factor AMP-activated protein kinase (AMPK), mitochondrial biogenesis stimulator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), and mitophagy/mitochondrial biogenesis factor Parkin were downregulated in control stretched myoblasts compared to non-stretched cells, while the specific mechanical loading protocol used also reduced the phosphorylation of unc-51-like autophagy-activating kinase 1 (p-ULK1) (p < 0.05), as well as the expression of myogenic factor 5 (Myf5) and myogenic factor 4 (myogenin) (p < 0.001). Interestingly, this mechanical loading resulted in increased PGC-1a and Parkin expression (p < 0.05) and induced the previously undetected BCL2 interacting protein 3-like (BNIP3L/NIX) and AMPK expression and p-ULK1 activation in the aged myoblasts. In addition, mechanical stretching differentially affected the expression of MRFs in aged cells, upregulating the early differentiation factor, Myf5 (p < 0.01), while downregulating the late differentiation factor myogenin (p < 0.001). Conclusions: These findings suggest the beneficial effects of mechanical loading on the impaired mitophagy and early differentiation in aged myoblasts, as indicated by the mitophagy initiation and the promotion of mitochondrial biogenesis in these cells. The mechanical loading-induced downregulation of mitophagy and myogenesis in the control myoblasts might indicate their loading-specific differential responses compared to the aged cells. Full article