Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia
Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia
复制标题
Nrf2缺乏促进骨骼肌衰老过程中自噬的增加趋势：肌肉减少症发生的潜在机制
DOI：
10.18632/aging.102990
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发表时间：
2020-04-15
期刊：
影响因子：
5.2
通讯作者：
Yu, Zhen
中科院分区：
文献类型：
--
作者：
Huang, Dong-Dong;Yan, Xia-Lin;Yu, Zhen
本研究旨在探讨核因子红细胞2相关因子2 （Nrf2）缺乏对骨骼肌自噬及肌少症发生的影响。LC3b、P62、Bnip3、Lamp-1和AMPK蛋白在年轻、中年、老年Nrf2−/−（敲除、KO）小鼠和年龄匹配野生型（WT） C57/BL6小鼠肌肉中的表达水平。用秋水仙碱作为自噬抑制剂，测定幼龄WT、幼龄KO、老年WT、老年KO小鼠的自噬通量。秋水仙碱诱导老年WT小鼠LC3b-II、P62、Bnip3、Lamp-1的积累均高于幼年小鼠。与WT小鼠相比，秋水仙碱诱导KO小鼠LC3b-II、P62、Bnip3、Lamp-1的积累显著增加，无论是年轻组还是老年组。AMPK和活性氧（ROS）在Nrf2 KO和年龄增加后不受调节，这与Nrf2 KO和年龄增加后自噬通量增加的趋势一致。Nrf2 KO和年龄增长导致指长伸肌和比目鱼肌横截面积减小。我们认为Nrf2缺乏和年龄增长可能激活AMPK和ROS信号，导致骨骼肌过度自噬激活，这可能是肌少症发生的潜在机制。
This study aims to explore the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency on skeletal muscle autophagy and the development of sarcopenia. LC3b, P62, Bnip3, Lamp-1, and AMPK protein levels were measured in muscle from young, middle-aged, old Nrf2−/− (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice. Autophagy flux was measured in young WT, young KO, old WT, old KO mice, using colchicine as autophagy inhibitor. There was a trend of higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 induced by colchicine in old WT mice compared with young WT mice. Colchicine induced a significantly higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 in KO mice compared with WT mice, both in the young and old groups. AMPK and reactive oxygen species (ROS) were unregulated following Nrf2 KO and increasing age, which was consistent with the increasing trend of autophagy flux following Nrf2 KO and increasing age. Nrf2 KO and increasing age caused decreased cross-sectional area of extensor digitorum longus and soleus muscles. We concluded that Nrf2 deficiency and increasing age may activate AMPK and ROS signals to cause excessive autophagy activation in skeletal muscle, which can be a potential mechanism for the development of sarcopenia.