Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture

Zheng,Yong; Hu,Cheng-Jun; Zhuo,Ru-Hong; Lei,Yue-Shan; Han,Na-Na; He,Liu

doi:10.3892/mmr.2014.2624

December-2014 Volume 10 Issue 6

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December-2014 Volume 10 Issue 6

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Article

Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture

Authors:
- Yong Zheng
- Cheng-Jun Hu
- Ru-Hong Zhuo
- Yue-Shan Lei
- Na-Na Han
- Liu He
View Affiliations / Copyright

Affiliations: Department of Anatomy and Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071, P.R. China, Department of Integrated Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Endodontics, School of Stomatology, Wuhan University, Wuhan, Hubei 430071, P.R. China
Pages: 3003-3008
|
Published online on: October 10, 2014

https://doi.org/10.3892/mmr.2014.2624
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Abstract

Following a limited number of cell divisions, mesenchymal stem cells (MSCs) undergo senescence, and these senescent cells maintain metabolic modification and remain viable for long periods. Autophagy, an intracellular bulk degradation process, provides a survival effect for cells under stress. In this study, the effect of autophagy on senescent MSCs was analyzed. Following serial passaging, rat MSCs underwent replicative senescence, characterized by positive staining for senescence-associated β-galactosidase (SA-β-gal), and increased expression levels of p16 and p21. During MSC senescence, the levels of autophagic activity were increased, a greater number of autophagic vacuoles were observed in senescent MSCs by transmission electron microscopy, acridine orange staining was elevated and the expression levels of autophagy‑related proteins (microtubule‑associated protein 1A/1B‑light chain 3-II, Atg7 and Atg12) were increased. The role of autophagy in MSC senescence was further investigated through pharmacological inhibition of autophagy with bafilomycin A1 and 3-methyladenine. Inhibition of autophagy by pharmacological means reduced the rate of positive staining for SA-β-gal and the expression levels of senescence‑related proteins. In conclusion, these findings suggest that autophagy is activated during senescence and the autophagic activity may be a requirement for maintaining the senescent state of MSCs.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Inhibition of autophagy alleviates the senescent state of rat mesenchymal stem cells during long-term culture

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Abstract

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