SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-06-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00103/full |
| _version_ | 1818547443382353920 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Huiqiang eChen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:06:47Z |
| format | Article |
| id | doaj.art-a96221a59d314e95b069d081d3afcb98 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T08:06:47Z |
| publishDate | 2014-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-a96221a59d314e95b069d081d3afcb982022-12-22T00:31:56ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652014-06-01610.3389/fnagi.2014.0010379276SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterinHuiqiang eChen0Huiqiang eChen1Xianbao eLiu2Xianbao eLiu3Wei eZhu4Han eChen5Han eChen6Xinyang eHu7Xinyang eHu8Zhi eJiang9Zhi eJiang10Yinchuan eXu11Yinchuan eXu12Lihan eWang13Lihan eWang14Yu eZhou15Yu eZhou16Panpan eChen17Panpan eChen18Na eZhang19Na eZhang20Dexing eHu21Dexing eHu22Ling eZhang23Yaping eWang24Yaping eWang25Qiyuan eXu26Qiyuan eXu27Rongrong eWu28Hong eYu29Jian-an eWang30Jian-an eWang31Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR ChinaSecond Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, PR China.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.http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00103/fullAgingMesenchymal Stem CellsTelomerasesenescenceSIRT1Shelterin |
| spellingShingle | 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 SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin Frontiers in Aging Neuroscience Aging Mesenchymal Stem Cells Telomerase senescence SIRT1 Shelterin |
| title | SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin |
| title_full | SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin |
| title_fullStr | SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin |
| title_full_unstemmed | SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin |
| title_short | SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin |
| title_sort | sirt1 ameliorates age related senescence of mesenchymal stem cells via modulating telomere shelterin |
| topic | Aging Mesenchymal Stem Cells Telomerase senescence SIRT1 Shelterin |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00103/full |
| work_keys_str_mv | AT huiqiangechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT huiqiangechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT xianbaoeliu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT xianbaoeliu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT weiezhu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT hanechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT hanechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT xinyangehu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT xinyangehu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT zhiejiang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT zhiejiang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yinchuanexu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yinchuanexu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT lihanewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT lihanewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yuezhou sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yuezhou sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT panpanechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT panpanechen sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT naezhang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT naezhang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT dexingehu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT dexingehu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT lingezhang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yapingewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT yapingewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT qiyuanexu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT qiyuanexu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT rongrongewu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT hongeyu sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT jiananewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin AT jiananewang sirt1amelioratesagerelatedsenescenceofmesenchymalstemcellsviamodulatingtelomereshelterin |