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

• Published in: Oncotarget Vol. 8; no. 10; pp. 16109 - 16121
• Main Authors: Dong, Dan, Cai, Guang-Yan, Ning, Yi-Chun, Wang, Jing-Chao, Lv, Yang, Hong, Quan, Cui, Shao-Yuan, Fu, Bo, Guo, Ya-Nan, Chen, Xiang-Mei
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 07-03-2017
• Subjects: Adult; Aging - drug effects; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Blotting, Western; Caloric Restriction; Cells, Cultured; Cellular Senescence - drug effects; Epithelial-Mesenchymal Transition - drug effects; Glucose - pharmacology; Humans; Hypoglycemic Agents - pharmacology; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Male; Metformin - pharmacology; Microscopy, Fluorescence; Rats, Sprague-Dawley; Research Paper: Gerotarget (Focus on Aging); Signal Transduction - drug effects; Stilbenes - pharmacology; TOR Serine-Threonine Kinases - metabolism; senescence; short-term caloric restriction; AMPK/mTOR signaling; Gerotarget; epithelial-mesenchymal transition; caloric restriction mimetics
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.14884

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.