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基于质谱的多组学鉴定恒河猴骨骼肌衰老特征的代谢特征。

Mass Spectrometry-Based Multiomics Identifies Metabolic Signatures of Sarcopenia in Rhesus Monkey Skeletal Muscle.

机构信息

Department of Cell and Regenerative Biology, University of Wisconsin─Madison, Madison, Wisconsin 53705, United States.

Department of Medicine, University of Wisconsin─Madison, Madison, Wisconsin 53705, United States.

出版信息

J Proteome Res. 2024 Aug 2;23(8):2845-2856. doi: 10.1021/acs.jproteome.3c00474. Epub 2023 Nov 22.

Abstract

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in "omics" technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offers new insights into the molecular mechanisms underlying sarcopenia for the evaluation and monitoring of a therapeutic treatment of sarcopenia.

摘要

肌肉减少症是一种进行性疾病,其特征是与年龄相关的骨骼肌质量和功能丧失。尽管近年来在确定肌肉减少症的分子决定因素方面取得了重大进展,但与年龄相关的收缩功能丧失的确切机制仍不清楚。“组学”技术的进步,包括基于质谱的蛋白质组学和代谢组学分析,为更好地理解肌肉减少症提供了巨大的机会。在此,我们对年轻、中年和老年恒河猴的股外侧肌进行了基于质谱的分析,以鉴定肌肉减少症的分子特征。在我们的蛋白质组学分析中,我们鉴定了随年龄变化的蛋白质,包括参与三磷酸腺苷和一磷酸腺苷代谢以及脂肪酸β氧化的蛋白质。在我们的非靶向代谢组学分析中,我们鉴定了随年龄变化的代谢物,这些代谢物主要与能量代谢有关,包括脂肪酸β氧化。对年龄反应蛋白和代谢物的途径分析揭示了肌肉结构和收缩以及脂质、碳水化合物和嘌呤代谢的变化。总之,这项研究发现了新的代谢特征,并为肌肉减少症的分子机制提供了新的见解,可用于评估和监测肌肉减少症的治疗。

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