RESUMO
Sarcopenia is a multifactorial process defined by loss of strength and skeletal muscle mass, which leads to a reduction in muscle cross-sectional area (CSA). Although resistance training (RT) has been indicated as a tool to counteract sarcopenia, the protein profile associated with skeletal muscle adaptations remains to be determined. We investigated the effects of 12 weeks of RT on the skeletal muscle proteome profile and CSA of young and older rats. Twenty-four animals were divided into four groups: young sedentary or trained and older sedentary or trained (six animals per group). A 12-week RT protocol was performed, which consisted of climbing a vertical ladder. The proteins from the gastrocnemius were analysed by LC-ESI-MS/MS. One-hundred and thirty-one proteins were identified, of which 28 were assessed between the groups. Ageing induced an increase in proteins associated with the glycolytic pathway, transport and stress response, which represent crucial mechanisms for muscle adaptation. RT upregulated metabolic enzymes, anti-oxidant activity and transport proteins, besides increasing hypertrophy, regardless of age, suggesting a beneficial adaptation to mitigate age-related sarcopenia. RT reduced muscle atrophy through the regulation of stress response and by increasing proteins related to energy production and transport, which in turn might protect tissue damage arising from exercise and ageing. SIGNIFICANCE OF THE STUDY: Protein abundance levels related to the metabolic process and stress response were increased in the aged muscle. RT proved to be an important intervention capable of inducing significant effects on muscle proteome regardless of ageing, due to upregulation of glycolytic enzymes, and anti-oxidant and transport proteins. This effect could lead to a beneficial adaptation in muscle structure, cellular function and overall homeostasis maintenance. This study contributes to better understanding of the basic biology of ageing and clarifies more profoundly the molecular networks behind physiological adaptations promoted by exercise training. Therefore, the results open new perspectives and insights for studies based on transcriptomics, metabolomics and functional assays.
Assuntos
Envelhecimento/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Proteômica , Animais , Masculino , Ratos , Ratos WistarRESUMO
Os avanços da biologia molecular, biologia celular e genética tem melhorado muito a nossa compreensão da biologia do músculo esquelético, demonstrando que as características biológicas das células satélites (CSs) são fundamentais no processo de regeneração muscular. O potencial terapêutico destas células vem sendo discutido pela literatura, por isso o entendimento do metabolismo e a regulação das células precursoras das fibras musculares merece atenção. Assim, o objetivo desta revisão narrativa é apresentar aspectos relacionados aos fatores de regulação das células satélites durante o processo de regeneração do músculo esquelético. A regeneração do músculo esquelético é um processo orquestrado que envolve a ativação e diferenciação das CSs. As interações celulares ocorrem com os diversos fatores miogênicos, de crescimento e hormonais. Entre eles destacam-se o HGF (fator de crescimento hepatocitário), IGF (fator de crescimento semelhante a insulina), MRFs (fatores regulatórios miogênicos), IL-6 (interleucina-6), VEGF (fator de crescimento vascular endotelial), Myf5 (fator miogênico 5), MRf4 (fator miogênico 4), MyoD (fator miogênico 1), androgênios e outros hormônios como a insulina. Todos estes fatores são dinâmicos e podem levar a uma maior compreensão da participação dessas células nos processos de regeneração tecidual. A interação com essas células promove ações positivas e negativas, levando a ativação ou inibição de suas atividades. O processo inflamatório e os fatores de crescimento atuam positivamente na diferenciação e proliferação celular. Entretanto, anti-inflamatórios, glicocorticoides e hormônios tireoidianos (T3) em excesso podem alterar o ciclo dessas células essenciais para o remodelamento tecidual. O entendimento de suas relações com as alterações fenotípicas e a sinalização que induzem modificações musculares é importante para o planejamento de estratégias de reabilitação e futuras terapias celulares.(AU)
The advance of molecular biology, cell biology and genetics has greatly improved our understanding of skeletal muscle biology, demonstrating that the biological characteristics of satellite cells (SCs) are essential in muscle regeneration. The therapeutic potential of these cells has been discussed in the literature, so the understanding of metabolism and regulation of precursor cells of the muscle fibers requires attention. The aim of this narrative review is to show aspects related to the regulatory factors of satellite cells during the process of skeletal muscle regeneration. Regeneration of skeletal muscle is an orchestrated process involving the activation and differentiation of SCs. The cellular interactions occur with various myogenic factors, growth factors and hormones. Stand out from HGF (Hepatocyte growth factor), IGF (insulin-like growth factor), MRFs (myogenic regulatory factors), IL-6 (interleukin-6), VEGF (vascular endothelial growth factor), Myf5 (myogenic factor 5), MRF4 (myogenic factor 4), MyoD (myogenic factor 1), androgens and other hormones such as insulin. All these factors are dynamic and can lead to a greater understanding of the role of cells in tissue regeneration processes. The interaction with these cells promotes positive and negative actions, leading to activation or inhibition of its activities. The inflammation and growth factors act positively on cell differentiation and proliferation. However, antiinflammatory, glucocorticoid and excess thyroid hormone (T3) may change the cycle of these cells essential to tissue remodeling. Understanding their relationship with the phenotypic changes and the signs inducing muscle changes is important for planning rehabilitation strategies and future cell therapies.(AU)