ArfGAP3 Protects Mitochondrial Function and Promotes Autophagy Through Rab5a‐Mediated Signals in Ageing Skeletal Muscle

作者：Mao Chen, Xiaoyu Huang, Bingshu Li, Ya Xiao, Liying Chen, Fangyi Zhu, Shasha Hong, Jianming Tang, Su‐Ting T. Li, Jie Min, Wenyi Jin, Yubiao Zhang, Lian Yang, Yang Li, Shufei Zhang, Hong Li · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.13725 · 被引用次数：7 · 研究领域：Autophagy in Disease and Therapy、Pelvic floor disorders treatments、Adenosine and Purinergic Signaling

BACKGROUND: Few researches have investigated the molecular mechanism responsible for the age-related loss of the pelvic floor muscle (PFM) mass and functionality-a pivotal contributor to pelvic organ prolapse and diminished physical well-being. ADP ribosylation factor GTPase activating protein 3 (ArfGAP3) is a member of ArfGAPs, which regulates the vesicular trafficking pathway and intracellular proteins transporting. However, its effects on skeletal muscle ageing remain largely unknown. METHODS: Mouse models of natural ageing and D-gal (D-galactose)-induced ageing were subject to analyse the structure, function and pathological alterations of the PFM and the expression of ArfGAP3. Stable ArfGAP3 knockdown and overexpression C2C12 cell lines were established to investigate the anti-senescence effects of ArfGAP3 and the underlying mechanisms in ageing process, complemented by Rab5a genetic intervention and mRFP-GFP-LC3 adenoviral particles transfection. In vivo experiments entailed ArfGAP3 overexpression in mice alongside autophagy inhibitor treatment, with assessments encompassing tissue mass, bladder leak point pressure (BLPP), submicroscopic structure, antioxidative stress system and muscle regeneration. RESULTS: Aged (24-month-old) mice exhibited significant physiological alterations in PFMs, including decreased muscle mass, diminished cross-sectional area (CSA), deteriorated supporting function (as evidenced by reduced BLPP), impaired autophagy and increased levels of oxi...