背景:肌肉减少症,与年龄有关的疾病,其特征是肌肉质量逐渐丧失,力量,和功能。它与肌管中异常的细胞器功能有关,包括线粒体和内质网(ER)。最近的研究表明,线粒体相关膜(MAM),连接线粒体和ER的位点,可能与骨骼肌老化有关。在这个竞技场上,黄精多糖(PSP)的潜力成为希望的灯塔。PSP,具有显著的抗氧化和抗衰老性能,正处于治疗革命的尖端,提供了一个有希望的策略来减轻肌肉减少症的影响。
目的:本研究的目的是探讨PSP对年龄相关性肌肉功能障碍的影响以及体内和体外的潜在机制。
方法:在这项调查中,我们使用D-半乳糖(D-gal)诱导C2C12肌管衰老的体外实验和老年小鼠的体内实验。评估了关键指标,包括活性氧(ROS)水平,线粒体功能,衰老相关标志物的表达,以及线粒体和MAM部分的关键蛋白。鉴定与线粒体和ER相关的差异表达基因(DEGs),并进行了生物信息学分析以探索潜在的机制。确定肌肉质量和功能以评估体内骨骼肌的数量和质量。
结果:PSP治疗有效缓解了C2C12肌管中D-gal引起的氧化应激和线粒体功能障碍,保持线粒体适应性并减少MAM形成。此外,PSP通过调节钙相关蛋白减弱了D-gal诱导的细胞内Ca2+浓度增加,DEGs的基因本体论(GO)分析也证实了这一点。在老年小鼠中,PSP增加肌肉质量和提高握力,悬挂时间,和其他参数,同时降低ROS水平并增加骨骼肌组织中的抗氧化酶活性。
结论:PSP可预防与年龄相关的肌肉损伤。提出的机制表明,通过调节MAM调节钙稳态会在骨骼肌衰老过程中产生有利的功能结果。这项研究的结果突出了PSP作为肌肉减少症和附属病理状况的治疗干预的前景。保证进一步调查。
BACKGROUND: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia.
OBJECTIVE: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro.
METHODS: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo.
RESULTS: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue.
CONCLUSIONS: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.