Gimcheon University

Advanced glycation end-products (AGEs) contribute to metabolic dysfunction and sarcopenia by promoting oxidative stress and inflammation. The therapeutic impact of exercise on AGEs-induced muscle deterioration and clinical relevance of skin autofluorescence (SAF) as a biomarker remain unclear. Therefore, we aimed to comprehensively investigate the physiological effects of AGEs using two complementary approaches.

This study comprised an animal experiment and a human observational study. In Experiment 1, male mice were administered methylglyoxal (MGO) to induce muscle atrophy and treated with or without treadmill exercise for 12 weeks. Muscle morphology, function, and atrophy-related markers were evaluated. In Experiment 2, 37 older adults (≥65 years) were stratified into low-SAF (<2.3 arbitrary units [AU]) and high-SAF (>2.7 AU) groups. Nε-(carboxymethyl)lysine (CML) and secreted protein acidic and rich in cysteine (SPARC) levels were compared.

In mice, muscle atrophy induced by MGO was associated with upregulation of MuRF1 and Atrogin-1, increased fibrosis, and suppression of MyoD and myogenin proteins. Aerobic exercise prevented these effects, restoring muscle mass, enhancing glucose transporter type 4 and myosin heavy chain expression, and reducing SMAD2/3 signaling. In humans, the high-SAF group showed elevated insulin resistance, higher CML, reduced SPARC, and poor performance in grip strength, five times sit-to-stand (STS), 2-min walk test, and STS power. SAF positively correlated with CML and negatively with muscle function.

Aerobic exercise mitigates AGEs-induced muscle deterioration through molecular and structural improvements. SAF and CML may serve as noninvasive biomarkers of functional decline in older adults. These findings highlight the potential of exercise to counteract sarcopenia associated with AGEs accumulation.

Methylglyoxal (MGO), a reactive glycolytic byproduct, contributes to skeletal muscle atrophy by promoting oxidative stress, inflammation, and protein degradation. This study investigated the therapeutic potential of trans-resveratrol and hesperidin (tRES-HESP) supplementation, alone or in combination with aerobic exercise, in ameliorating MGO-induced muscle dysfunction in mice. ICR mice were divided into five groups and treated with MGO, tRES-HESP, treadmill exercise, or both interventions over eight weeks. Muscle mass, grip strength, endurance performance, histopathology, and molecular biomarkers were assessed. Combined treatment with tRES-HESP and exercise significantly improved muscle function and morphology, restored muscle mass, and suppressed fibrosis. In terms of signaling pathways, the protective effects were associated with activation of the AMPK/SIRT1/PGC-1α pathway for mitochondrial biogenesis, stimulation of the AKT/mTOR pathway for muscle protein synthesis, suppression of MuRF1-mediated protein degradation, and upregulation of MyoD and MyHC, key markers of muscle regeneration and structural integrity. Additionally, inflammatory balance was restored via suppression of pro-inflammatory IL-6 and elevation of anti-inflammatory IL-10 levels. These findings highlight the synergistic benefits of combining polyphenol supplementation with aerobic exercise as a promising strategy for mitigating muscle atrophy under metabolic stress conditions.

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.