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Research Paper|Volume 9, Issue 5|pp 1359—1374

Aging-associated oxidative stress inhibits liver progenitor cell activation in mice

Yiji Cheng1, Xue Wang1, Bei Wang2, Hong Zhou2, Shipeng Dang2, Yufang Shi2, Li Hao3, Qingquan Luo1, Min Jin2, Qianjun Zhou1, Yanyun Zhang1,2
  • 1Shanghai Institute of Immunology and Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 3Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China

* * Equal contribution

Received: April 1, 2017Accepted: April 23, 2017Published: April 29, 2017
https://doi.org/10.18632/aging.101232

Copyright: © 2017 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Recent studies have discovered aging-associated changes of adult stem cells in various tissues and organs, which potentially contribute to the organismal aging. However, aging-associated changes of liver progenitor cells (LPCs) remain elusive. Employing young (2-month-old) and old (24-month-old) mice, we found diverse novel alterations in LPC activation during aging. LPCs in young mice could be activated and proliferate upon liver injury, whereas the counterparts in old mice failed to respond and proliferate, leading to the impaired liver regeneration. Surprisingly, isolated LPCs from young and old mice did not exhibit significant difference in their clonogenic and proliferative capacity. Later, we uncovered that the decreased activation and proliferation of LPCs were due to excessive reactive oxygen species produced by neutrophils infiltrated into niche, which was resulted from chemokine production from activated hepatic stellate cells during aging. This study demonstrates aging-associated changes in LPC activation and reveals critical roles for the stem cell niche, including neutrophils and hepatic stellate cells, in the negative regulation of LPCs during aging.