Hu Mengdie, Zhang Ying, Ding Hong, Chao Rui, Cao Zhidong
Department of Orthopedics, Central Hospital of Chongqing University, Chongqing, 400030, China.
Immun Ageing. 2025 Feb 14;22(1):7. doi: 10.1186/s12979-025-00499-8.
Advanced aging invariably triggers an overabundance of apoptosis, stemming from diminished autophagy or a disarray in cellular autophagic processes. This, in turn, leads to an accelerated breakdown of muscle proteins, which exacerbates the ongoing deterioration of skeletal muscle and intensifies the severity of senile sarcopenia. This study aimed to investigate the role and mechanism of miRNA-regulated autophagy in senile sarcopenia.
The miRNAs associated with sarcopenia were screened, and the target genes of significant miRNAs were predicted. The effects of significantly differentially expressed miRNA-144-5p on cell aging and autophagy were validated in vivo and in vitro.
The inhibition of miR-144-5p enhanced the multiplication of mouse myoblasts, increased the expression of MHC and autophagic markers LC3II/LC3I and Beclin-1, facilitated the formation of autophagosomes in mouse myoblasts, and reduced the number of aging cells and the expression of senescence-related proteins acetylated p53, p53, and p21 expression in mouse myoblasts. miR-144-5p affects myoblast senescence, myogenic differentiation, and autophagy by regulating the downstream target gene, Atg2A. Inhibiting miR-144-5p markedly increased the grip strength of the posterior limb in old mice, and the CSA of old mice and young mice was also markedly increased.
All experiments have demonstrated that miRNA-144-5p has a significant impact on the regulation of autophagy and the development of senile sarcopenia.
衰老加剧必然引发过度的细胞凋亡，这源于自噬功能减退或细胞自噬过程紊乱。反过来，这会导致肌肉蛋白加速分解，加剧骨骼肌的持续退化，加重老年肌肉减少症的严重程度。本研究旨在探讨miRNA调控的自噬在老年肌肉减少症中的作用及机制。
筛选与肌肉减少症相关的miRNA，并预测显著miRNA的靶基因。在体内和体外验证显著差异表达的miRNA-144-5p对细胞衰老和自噬的影响。
抑制miR-144-5p可增强小鼠成肌细胞的增殖，增加MHC以及自噬标志物LC3II/LC3I和Beclin-1的表达，促进小鼠成肌细胞中自噬体的形成，并减少衰老细胞数量以及小鼠成肌细胞中衰老相关蛋白乙酰化p53、p53和p21的表达。miR-144-5p通过调控下游靶基因Atg2A影响成肌细胞衰老、肌源性分化和自噬。抑制miR-144-5p可显著增加老年小鼠后肢握力，老年小鼠和年轻小鼠的横截面积也显著增加。
所有实验均表明，miRNA-144-5p对自噬调控及老年肌肉减少症的发展有显著影响。
