Open AccessAMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD + elevation
Author(s) -
Han Xiaojuan,
Tai Haoran,
Wang Xiaobo,
Wang Zhe,
Zhou Jiao,
Wei Xiawei,
Ding Yi,
Gong Hui,
Mo Chunfen,
Zhang Jie,
Qin Jianqiong,
Ma Yuanji,
Huang Ning,
Xiang Rong,
Xiao Hengyi
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12446
Subject(s) - ampk , autophagy , nad+ kinase , senescence , microbiology and biotechnology , amp activated protein kinase , oxidative stress , mitochondrion , flux (metallurgy) , intracellular , biology , homeostasis , oxidative phosphorylation , chemistry , phosphorylation , biochemistry , protein kinase a , apoptosis , enzyme , organic chemistry
Summary AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress‐induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide‐induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP ‐ RFP ‐ LC 3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD + levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD + synthesis. In addition, the mechanistic relationship of autophagic flux and NAD + synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress‐induced senescence by improving autophagic flux and NAD + homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD + homeostasis, and it is also valuable in the development of innovative strategies to combat aging.