Wu Zi-Jian, Li Ying-Chao, Zheng Yan, Zhou Meng-Qing, Li Hui, Wu Shi-Xiang, Zhao Xin-Yue, Yang Yu-Hong, Du Lei
Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, No. 105 Jiefang Road, Jinan, Shandong, 250013, China.
Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan, Shandong, 250012, China.
Food Funct. 2025 Jan 20;16(2):601-616. doi: 10.1039/d4fo04341c.
Sarcopenia frequently occurs with aging and leads to major adverse impacts in elderly individuals. The protective effects of omega-3 polyunsaturated fatty acids against aging-related sarcopenia have been demonstrated; however, the effect and underlying mechanism of EPA or DHA alone remain inconclusive. Hence, the present study was aimed to clarify the differential effects and possible mechanisms of EPA and DHA on aging-related sarcopenia. In this study, two-month-old and eighteen-month-old male C57BL/6J mice were fed with an AIN-93M diet and an AIN-93M diet containing 1% EPA or 1% DHA for 24 weeks, respectively. The results revealed that EPA and DHA supplementation effectively alleviated the decline in grip strength, skeletal muscle mass, and myofiber cross-sectional areas in aged mice, with EPA exhibiting a better effect against aging-related sarcopenia than DHA. The ROS scavenging role of EPA in aged skeletal muscle was also superior to that of DHA. Additionally, EPA showed a stronger role in improving protein turnover and myogenesis in aged skeletal muscle, as evidenced by suppressing the activation of FoxO3a and NF-κB, blunting the expression levels of muscle atrophy markers MAFbx and MuRF1, activating the PI3K/Akt/mTOR signaling pathway, and elevating MyoD expression. Moreover, EPA also revealed a better effect on inhibiting mitochondria- and endoplasmic reticulum stress-mediated apoptosis in aged skeletal muscle. Furthermore, EPA manifested a more pronounced effect on improving mitochondrial damage of aged skeletal muscle than DHA, and the reason might be due to its superior capability of regulating mitochondrial quality control, as clearly shown by enhancing mitochondrial biogenesis through the AMPK/PGC-1α-dependent pathway, restraining the loss of mitochondrial fusion and fission proteins including Opa1, Mfn2, and Fis1, and promoting mitophagy the PINK1/Parkin-dependent pathway.
肌肉减少症常随衰老而发生，并对老年人产生重大不利影响。ω-3多不饱和脂肪酸对与衰老相关的肌肉减少症具有保护作用已得到证实；然而，单独使用二十碳五烯酸（EPA）或二十二碳六烯酸（DHA）的效果及潜在机制仍无定论。因此，本研究旨在阐明EPA和DHA对与衰老相关的肌肉减少症的不同作用及可能机制。在本研究中，分别给2月龄和18月龄的雄性C57BL/6J小鼠喂食AIN-93M饮食以及含1% EPA或1% DHA的AIN-93M饮食，持续24周。结果显示，补充EPA和DHA可有效缓解老年小鼠握力、骨骼肌质量和肌纤维横截面积的下降，其中EPA对与衰老相关的肌肉减少症的改善效果优于DHA。EPA在老年骨骼肌中的活性氧清除作用也优于DHA。此外，EPA在改善老年骨骼肌蛋白质周转和肌生成方面作用更强，表现为抑制叉头框蛋白O3a（FoxO3a）和核因子κB（NF-κB）的激活，降低肌肉萎缩标志物肌肉萎缩F-box蛋白（MAFbx）和肌肉特异性泛素连接酶1（MuRF1）的表达水平，激活磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）信号通路，并提高肌细胞生成素（MyoD）的表达。此外，EPA在抑制老年骨骼肌中线粒体和内质网应激介导的细胞凋亡方面效果也更好。此外，EPA在改善老年骨骼肌线粒体损伤方面比DHA表现出更显著的效果，原因可能是其在调节线粒体质量控制方面具有更优能力，具体表现为通过腺苷酸活化蛋白激酶/过氧化物酶体增殖物激活受体γ共激活因子1α（AMPK/PGC-1α）依赖途径增强线粒体生物合成，抑制包括视神经萎缩蛋白1（Opa1）、线粒体融合蛋白2（Mfn2）和线粒体分裂蛋白1（Fis1）在内的线粒体融合和分裂蛋白的丢失，并通过磷酸化的含parkin的E3泛素蛋白连接酶1（PINK1）/帕金森病蛋白（Parkin）依赖途径促进线粒体自噬。
