Selvais Camille M, Davis-López de Carrizosa Maria A, Versele Romain, Dubuisson Nicolas, Noel Laurence, Brichard Sonia M, Abou-Samra Michel
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research, UCLouvain, 1200 Brussels, Belgium.
Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, 41004 Seville, Spain.
Antioxidants (Basel). 2024 Sep 3;13(9):1073. doi: 10.3390/antiox13091073.
Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if a shorter AR treatment could effectively offset sarcopenia in older mice. Two groups of old mice (20-23 months) were studied, one untreated (O) and one orally-treated with AR (O-AR) at 50 mg/kg/day for three months, compared with control 3-month-old young mice (Y) or 10-month-old young-adult mice (C-10). Results showed that AR remarkably inversed the loss of muscle mass by restoring the sarcopenia index and fiber count, which were greatly diminished with age. Additionally, AR successfully saved muscle quality of O mice by halving the accumulation of tubular aggregates and aberrant mitochondria, through AMPK pathway activation and enhanced autophagy. AR also bolstered muscle function by rescuing mitochondrial activity and improving exercise endurance. Finally, AR markedly curbed muscle fibrosis and mitigated local/systemic inflammation. Thus, a late three-month AR treatment successfully opposed sarcopenia and counteracted various hallmarks of aging, suggesting AR as a promising anti-aging therapy for skeletal muscles, potentially extending healthspan.
肌肉减少症以肌肉质量、质量和功能丧失为特征，在衰老过程中带来重大风险。我们之前证明，脂联素受体激动剂AdipoRon（AR）长期治疗可减轻中年肥胖小鼠的肌脂肪变性和肌肉退化。本研究旨在确定较短疗程的AR治疗是否能有效抵消老年小鼠的肌肉减少症。研究了两组老年小鼠（20 - 23个月），一组未治疗（O组），另一组以50 mg/kg/天的剂量口服AR治疗三个月（O - AR组），并与对照3个月大的年轻小鼠（Y组）或10个月大的青年成年小鼠（C - 10组）进行比较。结果显示，AR通过恢复随着年龄大幅下降的肌肉减少症指数和纤维数量，显著逆转了肌肉质量的损失。此外，AR通过激活AMPK途径和增强自噬，将管状聚集体和异常线粒体的积累减半，成功挽救了O组小鼠的肌肉质量。AR还通过恢复线粒体活性和提高运动耐力来增强肌肉功能。最后，AR显著抑制了肌肉纤维化并减轻了局部/全身炎症。因此，为期三个月的AR晚期治疗成功对抗了肌肉减少症并抵消了衰老的各种特征，表明AR作为一种有前景的骨骼肌抗衰老疗法，可能延长健康寿命。
