The effects of advanced glycation end products on muscle atrophy induced by denervation

Introduction: Previous studies have reported that advanced glycation end products (AGEs) impair skeletal muscle function. However, the effects of AGEs on denervation-induced muscle atrophy remain unclear. Therefore, this study aims to investigate the effects of AGEs on muscle atrophy caused by denervation. Method: In this study, we used 8-week-old ICR mice. The right hindlimb was denervated (Den group), while the left hindlimb served as a sham-operated control, with the nerve remaining undisturbed, and was subsequently closed (Sham group). Starting from the day of surgery, 25 milligrams (mg)/milliliters (mL) glyceraldehyde-induced AGEs (AGEs group) or 25 mg/mL bovine serum albumin (BSA group) was intraperitoneally administered at a dose of 0.5 mg/gram (g) once a day. The animals were sacrificed one week after surgery, and the soleus (SOL) and gastrocnemius (GAS) muscles were collected. The GAS muscle was used for Western blotting. Result: Compared to the sham-operated group, both the SOL and GAS muscles showed significant atrophy in the denervated group. Moreover, muscle atrophy was exacerbated in the denervated group treated with AGEs compared to the denervated group treated with BSA. The increased expression of MuRF1, a key regulator of protein breakdown, in the denervated group confirmed the induction of muscle atrophy by denervation. While the expression of 4EBP1, a regulator of protein synthesis, was upregulated in the denervated control group, this increase was abolished in the denervated group treated with AGEs, suggesting that AGEs inhibited protein synthesis. The activation of ULK1, an autophagy initiator, was enhanced in the denervated group treated with AGEs compared to the denervated control group. Conversely, the level of LC3 II, an autophagy marker, was decreased in the denervated group treated with AGEs. Conclusion: It was suggested that AGEs accelerate denervation-induced muscle atrophy by affecting protein synthesis systems and autophagy-related molecules in SOL and GAS muscles. This work was supported by JSPS KAKENHI Grant Numbers JP23K21598, JP22K18413, JP23K27973 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.