Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge

Abstract

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.

Exogenous and Endogenous Molecules Potentially Proficient to Modulate Mitophagy in Cardiac Disorders

“…They are now evolving as natural autophagy regulators with anti-aging properties. Interestingly, polyamine levels were considerably changed in the skeletal muscles of aged animals [90]. Furthermore, spermine could prevent hypoxia-induced ROS production and a reduction in mitophagy in cardiomyocytes [91].…”

Exploring the Gut Microbiota–Muscle Axis in Duchenne Muscular Dystrophy

“…They exhibit antioxidant, anti-inflammatory, and anti-apoptotic properties, influencing autophagy and mitochondrial apoptosis. Notably, polyamines are down-regulated in aged animals [ 40 ] and play a crucial role in regulating muscle atrophy and muscle fiber size through the rapamycin complex 1 (mTORC1), as well as the expression of spermine and spermidine synthase [ 41 ].…”

Wheat germ, a byproduct of the wheat milling industry, as a beneficial source of anti‐aging polyamines: A quantitative comparison of various forms

“…Polyamine‐rich foods are beneficial for aging retardation and delay, as long‐term oral consumption leads to high levels of polyamines in the blood, increasing cell proliferation, longevity, skin rejuvenation, and hair and nail growth (Oryza Oil & Fat Chemical Co, 2011 ). This also lowers the risk of cardiovascular disease, chronic neurological diseases, chronic inflammatory diseases, rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and cancer (Galasso et al, 2023 ; Karouzakis et al, 2012 ; Makletsova et al, 2022 ; Novita Sari et al, 2021 ; Polis & David Karasik, 2021 ; Saiki et al, 2019 ; Tong & Hill, 2017 ). Spermidine, spermine, and putrescine are the most abundant polyamines in living organisms and can be found in various foods (Nonami, 2002 ).…”