Frontiers in Aging Neuroscience (Jun 2014)
SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin
- Huiqiang eChen,
- Huiqiang eChen,
- Xianbao eLiu,
- Xianbao eLiu,
- Wei eZhu,
- Han eChen,
- Han eChen,
- Xinyang eHu,
- Xinyang eHu,
- Zhi eJiang,
- Zhi eJiang,
- Yinchuan eXu,
- Yinchuan eXu,
- Lihan eWang,
- Lihan eWang,
- Yu eZhou,
- Yu eZhou,
- Panpan eChen,
- Panpan eChen,
- Na eZhang,
- Na eZhang,
- Dexing eHu,
- Dexing eHu,
- Ling eZhang,
- Yaping eWang,
- Yaping eWang,
- Qiyuan eXu,
- Qiyuan eXu,
- Rongrong eWu,
- Hong eYu,
- Jian-an eWang,
- Jian-an eWang
Affiliations
- Huiqiang eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Huiqiang eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Xianbao eLiu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Xianbao eLiu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Wei eZhu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Han eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Han eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Xinyang eHu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Xinyang eHu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Zhi eJiang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Zhi eJiang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Yinchuan eXu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Yinchuan eXu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Lihan eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Lihan eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Yu eZhou
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Yu eZhou
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Panpan eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Panpan eChen
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Na eZhang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Na eZhang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Dexing eHu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Dexing eHu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Ling eZhang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Yaping eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Yaping eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Qiyuan eXu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Qiyuan eXu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Rongrong eWu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Hong eYu
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- Jian-an eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China
- Jian-an eWang
- Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.
- DOI
- https://doi.org/10.3389/fnagi.2014.00103
- Journal volume & issue
-
Vol. 6
Abstract
Age-related mesenchymal stem cells (MSCs) senescence, which impairs its tissue repair capacity in vivo and hence compromises the effects of MSCs-based therapy in clinical applications, is closely related to aging and aging-related diseases. Here, we demonstrated the effect of SIRT1, a NAD+-dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in young MSCs induces cellular senescence and inhibits cellular proliferation ability whereas overexpression of SIRT1 in aged MSCs reversed the cellular senescence and regained its proliferation capacity, suggesting that SIRT1 could modulate age-induced MSCs senescence. Aging-related proteins, P16 and P21, might be involved in SIRT1-mediated anti-aging effect on MSCs. SIRT1 could positively modulate age-related DNA damage in MSCs. In addition, SIRT1 could induce telomerase reverse transcriptase (TERT) expression and consequently enhance telomerase activity, however, no significant change was observed in telomere length. Moreover, SIRT1 could positively regulate TPP1, an important member of telomere shelterin, expression. Together, these results demonstrate that SIRT1 dampens age-related MSCs senescence, which was correlated with the up-regulation of TPP1 expression, telomerase activity and down-regulation of DNA damage.
Keywords
