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Autophagy controls mesenchymal stem cell properties and senescence during bone aging
Author(s) -
Ma Yang,
Qi Meng,
An Ying,
Zhang Liqiang,
Yang Rui,
Doro Daniel H,
Liu Wenjia,
Jin Yan
Publication year - 2018
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.12709
Subject(s) - autophagy , biology , senescence , mesenchymal stem cell , stem cell , microbiology and biotechnology , adipogenesis , cellular differentiation , reactive oxygen species , genetics , apoptosis , gene
Summary Bone marrow‐derived mesenchymal stem cells ( BMMSC s) exhibit degenerative changes, including imbalanced differentiation and reduced proliferation during aging, that contribute to age‐related bone loss. We demonstrate here that autophagy is significantly reduced in aged BMMSC s compared with young BMMSC s. The autophagy inhibitor 3‐methyladenine (3‐ MA ) could turn young BMMSC s into a relatively aged state by reducing their osteogenic differentiation and proliferation capacity and enhancing their adipogenic differentiation capacity. Accordingly, the autophagy activator rapamycin could restore the biological properties of aged BMMSC s by increasing osteogenic differentiation and proliferation capacity and decreasing adipogenic differentiation capacity. Possible underlying mechanisms were explored, and the analysis revealed that autophagy could affect reactive oxygen species and p53 levels, thus regulating biological properties of BMMSC s. In an in vivo study, we found that activation of autophagy restored bone loss in aged mice. In conclusion, our results suggest that autophagy plays a pivotal role in the aging of BMMSC s, and activation of autophagy could partially reverse this aging and may represent a potential therapeutic avenue to clinically treat age‐related bone loss.

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