Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy.
U.O. Laboratorio di Morfologia Umana Applicata, I.R.C.C.S. Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy.
Int J Mol Sci. 2023 Jun 6;24(12):9798. doi: 10.3390/ijms24129798.
Autophagy dysregulation is commonplace in the pathogenesis of several invalidating diseases, such as musculoskeletal diseases. Polyamines, as spermidine and spermine, are small aliphatic cations essential for cell growth and differentiation, with multiple antioxidant, anti-inflammatory, and anti-apoptotic effects. Remarkably, they are emerging as natural autophagy regulators with strong anti-aging effects. Polyamine levels were significantly altered in the skeletal muscles of aged animals. Therefore, supplementation of spermine and spermidine may be important to prevent or treat muscle atrophy. Recent in vitro and in vivo experimental studies indicate that spermidine reverses dysfunctional autophagy and stimulates mitophagy in muscles and heart, preventing senescence. Physical exercise, as polyamines, regulates skeletal muscle mass inducing proper autophagy and mitophagy. This narrative review focuses on the latest evidence regarding the efficacy of polyamines and exercise as autophagy inducers, alone or coupled, in alleviating sarcopenia and aging-dependent musculoskeletal diseases. A comprehensive description of overall autophagic steps in muscle, polyamine metabolic pathways, and effects of the role of autophagy inducers played by both polyamines and exercise has been presented. Although literature shows few data in regard to this controversial topic, interesting effects on muscle atrophy in murine models have emerged when the two "autophagy-inducers" were combined. We hope these findings, with caution, can encourage researchers to continue investigating in this direction. In particular, if these novel insights could be confirmed in further in vivo and clinical studies, and the two synergic treatments could be optimized in terms of dose and duration, then polyamine supplementation and physical exercise might have a clinical potential in sarcopenia, and more importantly, implications for a healthy lifestyle in the elderly population.
自噬失调在几种无效疾病的发病机制中很常见，例如肌肉骨骼疾病。多胺，如精脒和精胺，是细胞生长和分化所必需的小脂族阳离子，具有多种抗氧化、抗炎和抗细胞凋亡作用。值得注意的是，它们作为天然自噬调节剂具有很强的抗衰老作用。多胺水平在老年动物的骨骼肌中发生了明显改变。因此，补充精脒和精胺可能对预防或治疗肌肉萎缩很重要。最近的体外和体内实验研究表明，精脒可以逆转肌肉和心脏中功能失调的自噬并刺激自噬体，防止衰老。与多胺一样，体育锻炼也可以调节骨骼肌质量，诱导适当的自噬和自噬体。本综述重点介绍了多胺和运动作为自噬诱导剂的最新证据，单独或联合使用，在缓解肌肉减少症和与衰老相关的肌肉骨骼疾病方面的疗效。本文全面描述了肌肉中整体自噬步骤、多胺代谢途径以及自噬诱导剂在多胺和运动中发挥作用的机制。尽管文献中关于这个有争议的主题的数据很少，但当两种“自噬诱导剂”结合使用时，在小鼠模型中观察到对肌肉萎缩的有趣影响。我们希望这些发现能够谨慎地鼓励研究人员继续在这一方向进行研究。特别是，如果这些新的见解能够在进一步的体内和临床研究中得到证实，并且两种协同治疗能够在剂量和时间上得到优化，那么多胺补充和体育锻炼可能在肌肉减少症方面具有临床潜力，更重要的是，对老年人的健康生活方式具有重要意义。
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