Search Results (1,038)

Background: ETAS^®, a standardized extract of Asparagus officinalis stem, has been found to alleviate cognitive impairment in senescence-accelerated mice prone 8 (SAMP8) and is now considered a functional food in aging. The present study aimed to investigate the impacts of ETAS^® on relieving aging-related muscle atrophy in SAMP8 mice. Methods: The SAMP8 mice were fed a regular diet supplemented with 200 or 1000 mg/kg BW ETAS^®50 for 12 weeks. Grip strength, muscle mass, and molecular markers of protein synthesis, degradation, and mitochondrial quality were assessed. Results: We found that ETAS^® significantly increased grip strength and muscle mass in SAMP8 mice. At the molecular level, ETAS^® significantly upregulated protein synthesis via PI3K/Akt/mTOR/p70S6K and downregulated protein degradation via FoxO1a/atrogin-1 and MuRF-1 and myostatin via NFκB expression. In addition, ETAS^® improved mitochondrial quality via promoting mitochondrial biogenesis genes, oxidative respiration genes, fusion/fission genes, PGC1α, and PINK1 proteins and maintained the autophagic flux via reducing ATG13, LC3-II/LC3-I, and p62. Conclusions: ETAS^® exerts beneficial effects on sarcopenia by modulating the positive protein turnover and improving mitochondrial quality in aging. Full article

Polyphenols have been widely recognized for their potential anti-obesity effects. This study aimed to evaluate the impact of a polyphenol compound-epigallocatechin-3-gallate, quercetin, and rutin (EQR) on obesity-related parameters and gut microbiota composition. After four weeks of high-fat diet (HFD) induction, the obese Wistar male rats received EQR treatment for an additional four weeks. EQR supplementation significantly reduced body weight gain, feed efficiency, adipose tissue accumulation, and liver lipid content in obese rats. Additionally, it enhanced fecal short-chain fatty acid (SCFA) levels and modulated gut microbiota composition. Specifically, EQR treatment significantly induced Fusobacteria, Fusobacteriaceae, Christensenellaceae, Christensenellaceae R-7 group, Lachnoclostridium, Enterorhabdus, and Parvibacter levels and reduced Deferribacteres and Mucispirillum levels. Gene expression analysis in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) revealed that EQR upregulated the expression of liver PPAR-α, WAT SIRT-1, and BAT PGC-1α, while downregulating liver PPAR-γ, liver FATP-1, and WAT FAS, indicating its role in promoting fatty acid oxidation and thermogenesis, as well as suppressing lipid synthesis and transport. In conclusion, EQR demonstrated significant anti-obesity effects by modulating gut microbiota and lipid metabolism, suggesting its potential as a functional ingredient for obesity management. Full article

Stem cell therapies, including mesenchymal (MSCs) and haematopoietic stem cells (HSCs), have shown promise in neurodegenerative diseases. Here, we investigated the therapeutic effects of a defined combination of unmanipulated MSCs and CD34⁺ HSCs, termed Neuro-Cells (NC), in a murine model of Alzheimer’s disease (AD), the APPswe/PS1dE9 mouse. At 12 months of age, mice received intracisternal injections of NC (1.39 × 10⁶ MSCs + 5 × 10⁵ HSCs) or vehicle. After 45 days, behavioural testing, immunohistochemical analyses of amyloid plaque density (APD), and cortical gene expression profiling were conducted. NC-treated APP/PS1 mice exhibited preserved object recognition memory and reduced anxiety-like behaviours, contrasting with deficits observed in untreated transgenic controls. Histologically, NC treatment significantly reduced the density of small amyloid plaques (<50 μm²) in the hippocampus and thalamus, and total plaque burden in the thalamus. Gene expression analysis revealed that NC treatment normalised or reversed disease-associated changes in insulin receptor (IR) signalling and neurotrophic pathways. Specifically, NC increased expression of Bdnf, Irs2, and Pgc-1α, while attenuating aberrant upregulation of Insr, Igf1r, and markers of ageing and AD-related pathology (Sirt1, Gdf15, Arc, Egr1, Cldn5). These findings indicate that NC therapy mitigates behavioural and molecular hallmarks of AD, potentially via restoration of BDNF and insulin receptor-mediated signalling. Full article

Fenofibrate (FF), a lipid-lowering drug, may decrease the risk of cardiovascular diseases in some pathological settings, yet data on its cardiac effects in physiological aging is scarce. To determine FF and age effects on the heart’s morphology and expression of metabolism-related genes, we treated young and old male rats for 30 days with 0.1% or 0.5% FF. FF did not affect serum activities of LDH and creatine kinase in both age groups. Upon FF treatment the structure of the heart muscle did not change in young rats; however, 0.5% FF increased the abundance of collagen fibers in old rats, and lipid accumulation in cardiomyocytes in young and old animals. FF increased immunoreactivity of the hypertrophy marker NPPA that was more pronounced in old than in young rats, while VEGFB immunoreactivity did not change. FF upregulated phospho-AMPK and PGC1α protein levels only in the cardiac muscle of old rats, while in both age groups it mildly increased the expression of selected fatty acid oxidation genes. We conclude that the cardiac muscle response to FF is dose-dependent and influenced by age. The observed negative impact of high-dose FF in the hearts of aged rats underscores the importance of dose optimization in the elderly. Full article

The capability to generate induced pluripotent stem cells (iPSCs) from adult somatic cells, enabling them to differentiate into any cell type, has been demonstrated in several studies. In humans and mice, iPSCs have been shown to differentiate into primordial germ cells (PGCs), spermatozoa, and oocytes. However, research on iPSCs in deer is novel. Despite the necessity for establishing germplasm banks from endangered cervid species, the collection and cryopreservation of gametes and embryos have proven complex for this group. Therefore, the focus of this study was to establish protocols for deriving stable iPSC lines from Blastocerus dichotomus (Marsh deer) using primary cells derived from antler, adipose tissue, or skin, with the ultimate goal of producing viable gametes in the future. To achieve this, two main reprogramming approaches were tested: (1) transfection using PiggyBac transposons (plasmid PB-TET-MKOS) delivered via electroporation and (2) lentiviral transduction using the STEMCCA system with either human (hOSKM) or murine (mOSKM) reprogramming factors. Both systems utilized murine embryonic fibroblasts (MEFs) as feeder cells. The PiggyBac system was further supplemented with a culture medium containing small molecules to aid reprogramming, including a GSK inhibitor, MEK inhibitor, ALK/TGF inhibitor, and thiazovivin. Initial colony formation was observed; however, these colonies failed to expand post-selection. Despite these challenges, important insights were gained that will inform and guide future studies toward the successful generation of iPSCs in deer. Full article

Regular physical activity induces a dynamic crosstalk between skeletal muscle and adipose tissue, modulating the key molecular pathways that underlie metabolic flexibility, mitochondrial function, and inflammation. This review highlights the role of myokines and adipokines—particularly IL-6, irisin, leptin, and adiponectin—in orchestrating muscle–adipose tissue communication during exercise. Exercise stimulates AMPK, PGC-1α, and SIRT1 signaling, promoting mitochondrial biogenesis, fatty acid oxidation, and autophagy, while also regulating muscle hypertrophy through the PI3K/Akt/mTOR and Wnt/β-catenin pathways. Simultaneously, adipose-derived factors like leptin and adiponectin modulate skeletal muscle metabolism via JAK/STAT3 and AdipoR1-mediated AMPK activation. Additionally, emerging exercise mimetics such as the mitochondrial-derived peptide MOTS-c and myostatin inhibitors are highlighted for their roles in increasing muscle mass, the browning of white adipose tissue, and improving systemic metabolic function. The review also addresses the role of anti-inflammatory compounds, including omega-3 polyunsaturated fatty acids and low-dose aspirin, in mitigating NF-κB and IL-6 signaling to protect mitochondrial health. The resulting metabolic flexibility, defined as the ability to efficiently switch between lipid and glucose oxidation, is enhanced through repeated exercise, counteracting age- and disease-related mitochondrial and functional decline. Together, these adaptations demonstrate the importance of inter-tissue signaling in maintaining energy homeostasis and preventing sarcopenia, obesity, and insulin resistance. Finally, here we propose a stratified treatment algorithm based on common age-related comorbidities, offering a framework for precision-based interventions that may offer a promising strategy to preserve metabolic plasticity and delay the age-associated decline in cardiometabolic health. Full article

Obesity and associated metabolic disorders are rising globally, necessitating effective dietary strategies. CKDB-322, a formulation containing Lactiplantibacillus plantarum Q180 and Phaeodactylum tricornutum, was evaluated for anti-obesity efficacy using in vitro adipocyte differentiation and in vivo high-fat-diet (HFD)-induced obese mouse models. In 3T3-L1 cells, CKDB-322 suppressed adipogenesis by downregulating PPARγ and C/EBPα and enhancing glycerol release. In mice, 8 weeks of oral administration—particularly at the CKDB-322-M dose—significantly reduced body weight gain, adiposity, and serum glucose, triglyceride, and cholesterol levels without affecting liver function. Gene expression analysis revealed the strong inhibition of lipogenic markers (SREBP-1c, ACC, and FAS) in addition to activation of the fatty acid oxidation (CPT-1α and PPARα) and energy metabolism (PGC-1α and AMPK) pathways, with the most pronounced effects in the CKDB-322-M group, which also exhibited the greatest reduction in leptin. These molecular effects were confirmed histologically by decreased adipocyte hypertrophy and ameliorated hepatic steatosis. Collectively, these findings demonstrate that CKDB-322 exerts lipid-modulatory effects through multiple pathways, supporting its potential as a novel functional dietary ingredient for obesity and metabolic disorder prevention. Full article

Background/Objectives: Sarcopenic obesity, defined by the coexistence of excessive fat accumulation and progressive muscle loss, is associated with an increased risk of metabolic dysfunction and physical disability. While 5,7-dimethoxyflavone (DMF), a bioactive flavone derived from Kaempferia parviflora, has demonstrated anti-obesity and muscle-preserving properties, its effects on sarcopenic obesity remain unclear. Methods: Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 6 weeks to induce sarcopenic obesity, followed by 8 weeks of continued HFD with the oral administration of DMF. Muscle function was assessed through grip strength and treadmill running tests, while muscle and fat volumes were measured using micro-CT. Mechanistic analyses were performed using gene expression and Western blot analysis. Results: DMF significantly reduced body weight, fat mass, and adipocyte size while enhancing grip strength, endurance, skeletal muscle mass, and the muscle fiber cross-sectional area. In the gastrocnemius muscle, DMF increased the gene expression of peroxisome proliferator-activated receptor gamma coactivator-1α (Ppargc1a) and its isoform Ppargc1a4, thereby promoting mitochondrial biogenesis. It also improved protein turnover by modulating protein synthesis and degradation via the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin signaling pathway. In subcutaneous and brown adipose tissues, DMF increased mitochondrial DNA content and the expression of thermogenic and beige adipocyte-related genes. These findings suggest that DMF alleviates sarcopenic obesity by improving mitochondrial function and regulating energy metabolism in both skeletal muscle and adipose tissues via PGC-1α-mediated pathways. Thus, DMF represents a promising therapeutic candidate for the integrated management of sarcopenic obesity. Full article

Gastric ulcer (GU) is a common gastrointestinal disorder that impacts quality of life. Currently, several drugs are available for GU treatment, including proton pump inhibitors like omeprazole (OMP); however, their use is limited by numerous potential adverse effects. Glycyrrhizic acid (GLY), a natural anti-inflammatory agent, exhibits promising gastroprotective properties; however, its use is likewise limited by numerous potential adverse effects. This study aimed to synthesize GLY nanoparticles (GLY-NPs) to enhance their therapeutic potential and to comparatively evaluate their efficacy against OMP in an ethanol-induced GU in male Wistar rats. GLY-NPs were synthesized via a hydrothermal method and characterized using TEM, XRD, FTIR, and zeta potential analyses. In vivo, GLY-NPs significantly attenuated gastric mucosal damage compared to OMP, as evidenced by macroscopic and histopathological analyses. Biochemical assays revealed that GLY-NPs markedly improved antioxidant defenses by elevating SOD, catalase, and glutathione peroxidase activities while reducing MDA levels, surpassing the effects of OMP. Furthermore, GLY-NPs modulated inflammatory responses by downregulating p38 MAPK, NF-κB, and TNF-α expression, concomitant with upregulation of the anti-inflammatory cytokine IL-10. Mechanistic insights indicated that GLY-NPs favorably regulated key signaling pathways implicated in gastric mucosal protection, including suppression of the JAK2/STAT3 and TGF-β1/Smad3 pathways, alongside activation of the SIRT1/FOXO1/PGC-1α axis. In conclusion, these findings indicate that GLY-NPs offer higher gastroprotective effects relative to traditional OMP therapy through comprehensive modulation of oxidative stress, inflammation, and molecular signaling pathways. This study highlights GLY-NPs as a potent nanotherapeutic candidate for the effective management of GU. Full article

Migraine is a complex neurological disorder characterized by recurrent headaches and sensory disturbances. Emerging evidence highlights a critical role for mitochondrial dysfunction in migraine pathophysiology, including impairments in oxidative phosphorylation, disruptions in mitochondrial dynamics, and altered biogenesis. Experimental migraine models—ranging from nitroglycerin-induced attacks to inflammatory stimuli—consistently demonstrate mitochondrial swelling, cristae disruption, decreased ATP production, and increased oxidative stress. These findings are accompanied by the altered expression of key mitochondrial regulators such as PGC-1α, Drp1, and Mfn1. Recent studies have further identified distinct metabolic subtypes of mitochondria, including P5CS-containing subsets, which exhibit unique structural and functional profiles, including cristae loss and reduced ATP synthase expression. Notably, the mitochondrial alterations observed in migraine models show remarkable parallels to those described in P5CS-related mitochondrial subsets. These similarities suggest a potential mechanistic link between metabolic reprogramming within mitochondria and migraine pathogenesis. Understanding the contribution of these newly defined mitochondrial populations could offer novel insights into migraine biology and open new avenues for targeted therapeutic strategies. Full article

Sarcopenia, the progressive loss of skeletal muscle mass and function with age, significantly contributes to frailty and mortality in older adults. Notably, muscles do not age uniformly—some retain structure and strength well into old age. This review explores the mechanisms underlying differential resistance to muscle aging, with a focus on sarcopenia-resistant muscles. We analyzed current literature across molecular biology, genetics, and physiology to identify key regulators of muscle preservation during aging. Special attention was given to muscle fiber types, mitochondrial function, neuromuscular junctions, and satellite cell activity. Muscles dominated by slow-twitch (type I) fibers—such as the soleus, diaphragm, and extraocular muscles—demonstrate enhanced resistance to sarcopenia. This resilience is linked to sustained oxidative metabolism, high mitochondrial density, robust antioxidant defenses, and preserved regenerative capacity. Key molecular pathways include mTOR, PGC-1α, and SIRT1/6, while genetic variants in ACTN3, MSTN, and FOXO3 contribute to interindividual differences. In contrast, fast-twitch muscles are more vulnerable due to lower oxidative capacity and satellite cell depletion. Unique innervation patterns and neurotrophic support further protect muscles like extraocular muscles from age-related atrophy. Resistance to sarcopenia is driven by a complex interplay of intrinsic and extrinsic factors. Understanding why specific muscles age more slowly provides insights into muscle resilience and suggests novel strategies for targeted prevention and therapy. Expanding research beyond traditionally studied muscles is essential to develop comprehensive interventions to preserve mobility and independence in aging populations. Full article

Pulmonary hypertension syndrome (PHS), a metabolic disorder causing economic losses in broilers, arises from hypoxia-induced portal hypertension and liver cirrhosis, triggering mitochondrial oxidative damage, excessive ROS production, and altered mitochondrial biogenesis. This study explored terpinen-4-ol (T4O), known for antimicrobial and anti-inflammatory properties, in mitigating PHS. Broilers were divided into four groups, including PHS-affected birds with/without T4O supplementation. Analyses revealed that PHS birds exhibited reduced antioxidant capacity, elevated MDA and ROS levels, increased mitochondrial numbers, and upregulated expression of oxidative stress markers (Keap1, HO-1, Nrf-2) and mitochondrial biogenesis regulators (PGC-1α, Nrf-1, Tfam). T4O administration enhanced antioxidant activity, reduced ROS and MDA, suppressed compensatory mitochondrial proliferation, and downregulated Keap1/Nrf-2 and mitochondrial biogenesis pathways. These effects suggest that T4O alleviates hypoxia-driven oxidative stress and mitochondrial dysfunction in broilers. Findings highlight T4O’s potential as a therapeutic agent to mitigate PHS-related losses in poultry production. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Circadian rhythms are intrinsic 24 h cycles that regulate metabolic processes across multiple tissues, with skeletal muscle emerging as a central node in this temporal network. Muscle clocks govern gene expression, fuel utilisation, mitochondrial function, and insulin sensitivity, thereby maintaining systemic energy homeostasis. However, circadian misalignment, whether due to behavioural disruption, nutrient excess, or metabolic disease, impairs these rhythms and contributes to insulin resistance, and the development of obesity, and type 2 diabetes mellitus. Notably, the muscle clock remains responsive to non-photic cues, particularly exercise, which can reset and amplify circadian rhythms even in metabolically impaired states. This work synthesises multi-level evidence from rodent models, human trials, and in vitro studies to elucidate the role of skeletal muscle clocks in circadian metabolic health. It explores how exercise entrains the muscle clock via molecular pathways involving AMPK, SIRT1, and PGC-1α, and highlights the time-of-day dependency of these effects. Emerging data demonstrate that optimally timed exercise enhances glucose uptake, mitochondrial biogenesis, and circadian gene expression more effectively than time-agnostic training, especially in individuals with metabolic dysfunction. Finally, findings are integrated from multi-omic approaches that have uncovered dynamic, time-dependent molecular signatures that underpin circadian regulation and its disruption in obesity. These technologies are uncovering biomarkers and signalling nodes that may inform personalised, temporally targeted interventions. By combining mechanistic insights with translational implications, this review positions skeletal muscle clocks as both regulators and therapeutic targets in metabolic disease. It offers a conceptual framework for chrono-exercise strategies and highlights the promise of multi-omics in developing precision chrono-medicine approaches aimed at restoring circadian alignment and improving metabolic health outcomes. Full article

The stomach has been a highly conserved organ throughout vertebrate evolution; however, there are now over 20 lineages composed of monotremes, lungfish and teleost fish displaying a secondary loss of stomach function and morphology. This “agastric phenotype” has evolved convergently and is typified by a loss of gastric glands and gastric acid secretion and a near-to-complete loss of storage capacity of the stomach. All agastric species have lost the genes for gastric enzymes (Pga and Pgc) and proton pump subunits (Atp4a and Atp4b), and gastrin (Gast) has been lost in monotremes. As a key gastric hormone, the conservation of gastrin has not yet been investigated in the lungfish or agastric teleosts, and it is unclear how the loss of gastrin affects the evolution and selection of the native receptor (Cckbr), gastrin-releasing peptide (Grp) and gastrin-releasing peptide receptor (Grpr) in vertebrates. Furthermore, there are still many genes implicated in gastric development and function which have yet to be associated with the agastric phenotype. We analysed the evolution, selection and conservation of the gastrin pathway and a novel gastric gene repertoire (Gkn1, Gkn2, Tff1, Tff2, Vsig1 and Anxa10) to determine the correlation with the agastric phenotype. We found that the loss of gastrin or its associated genes does not correlate with the agastric phenotype, and their conservation is due to multiple pleiotropic roles throughout vertebrate evolution. We found a loss of the gastric gene repertoire in the agastric phenotype, except in the echidna, which retained several genes (Gkn1, Tff2 and Vsig1). Our findings suggest that the gastrin physiological pathway evolved differently in pleiotropic roles throughout vertebrate evolution and support the convergent evolution of the agastric phenotype through shared independent gene-loss events. Full article