Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Alleviation of senescence and epithelial-mesenchymal transition in aging kidney by short-term caloric restriction and caloric restriction mimetics via modulation of AMPK/mTOR signaling

Dan Dong, Guang-yan Cai, _ Yi-chun Ning, Jing-chao Wang, Yang Lv, Quan Hong, Shao-yuan Cui, Bo Fu, Ya-nan Guo, Xiang-mei Chen

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Oncotarget. 2017; 8:16109-16121. https://doi.org/10.18632/oncotarget.14884

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Abstract

Dan Dong1,2, Guang-yan Cai1, Yi-chun Ning1, Jing-chao Wang1, Yang Lv1, Quan Hong1, Shao-yuan Cui1, Bo Fu1, Ya-nan Guo1 and Xiang-mei Chen1

1 Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, P. R. China

2 Department of Nephrology, First Hospital of Jilin University, Changchun, Jilin, P. R. China

Correspondence to:

Guang-yan Cai, email:

Keywords: senescence, epithelial-mesenchymal transition, short-term caloric restriction, caloric restriction mimetics, AMPK/mTOR signaling, Gerotarget

Received: November 04, 2016 Accepted: January 16, 2017 Published: January 28, 2017

Abstract

Renal fibrosis contributes to declining renal function in the elderly. What is unclear however, is whether epithelial-mesenchymal transition (EMT) contributes to this age-related renal fibrosis. Here, we analyzed indicators of EMT during kidney aging and investigated the protective effects and mechanisms of short-term regimens of caloric restriction (CR) or caloric restriction mimetics (CRMs), including resveratrol and metformin. High glucose was used to induce premature senescence and EMT in human primary proximal tubular cells (PTCs) in vitro. To test the role of AMPK-mTOR signaling, siRNA was used to deplete AMPK. Cellular senescence and AMPK-mTOR signaling markers associated with EMT were detected. CR or CRMs treatment alleviated age-related EMT in aging kidneys, which was accompanied by activation of AMPK-mTOR signaling. High glucose induced premature senescence and EMT in PTCs in vitro, which was accompanied by down-regulation of AMPK/mTOR signaling. CRMs alleviated high glucose-induced senescence and EMT via stimulation of AMPK/mTOR signaling. Activation of AMPK/mTOR signaling protected PTCs from high glucose-induced EMT and cellular senescence. Short-term regimens of CR and CRMs alleviated age-related EMT via AMPK-mTOR signaling, suggesting a potential approach to reducing renal fibrosis during aging.

Author Information

Dan Dong

Guang-yan Cai
Primary Contact  _

Yi-chun Ning

Jing-chao Wang

Yang Lv

Quan Hong

Shao-yuan Cui

Bo Fu

Ya-nan Guo

Xiang-mei Chen


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