Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia

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 an...

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Published in:Aging (Albany, NY.) NY.), 2020-04, Vol.12 (7), p.5977-5991
Main Authors: Huang, Dong-Dong, Yan, Xia-Lin, Fan, Sheng-Dong, Chen, Xi-Yi, Yan, Jing-Yi, Dong, Qian-Tong, Chen, Wei-Zhe, Liu, Na-Xin, Chen, Xiao-Lei, Yu, Zhen
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Autophagy - drug effects
Autophagy - physiology
Colchicine - pharmacology
Mice
Mice, Knockout
Muscle, Skeletal - metabolism
NF-E2-Related Factor 2 - deficiency
NF-E2-Related Factor 2 - metabolism
Protein Kinases - metabolism
Reactive Oxygen Species - metabolism
Research Paper
Sarcopenia - metabolism
Tubulin Modulators - pharmacology
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.102990