Prolonged unbalanced growth induces cellular senescence markers linked with mechano transduction in normal and tumor cells.
Prolonged unbalanced growth induces cellular senescence markers linked with mechano transduction in normal and tumor cells.
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DOI：
10.1016/j.bbrc.2005.07.106
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发表时间：
2005-09
影响因子：
3.1
通讯作者：
Emi Sumikawa;Y. Matsumoto;Risa Sakemura;M. Fujii;D. Ayusawa
中科院分区：
文献类型：
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作者：
Emi Sumikawa;Y. Matsumoto;Risa Sakemura;M. Fujii;D. Ayusawa
细胞衰老是由多种途径诱导的，因此被认为是由多种途径介导的。我们发现，长期不平衡的增长，由于延迟的DNA复制elyoung的衰老样现象，无论细胞类型。事实上，通过各种方法适度抑制DNA复制会导致细胞肿胀、细胞骨架改变和不规则增大的扁平细胞形状。这些细胞上调衰老相关基因，最终失去分裂潜力。这些定义细胞衰老的表型，通过减少蛋白质合成或阻断MAP激酶家族的ERK几乎被逆转。这些结果表明，细胞衰老是与机械力转导相关的长期不平衡生长的表现，并且可以通过至少两种不同的方式来防止。
Cellular senescence is induced by diverse means and hence thought to be mediated by multiple pathways. We show that prolonged unbalanced growth due to retardation of DNA replication elicits a senescence-like phenomenon irrespective of the cell type. In fact, modest inhibition of DNA replication by various means led to cell swelling, cytoskeletal alterations, and irregularly enlarged, flat cell shape. Such cells upregulated senescence-associated genes, and eventually lost division potential. These phenotypes, which define cellular senescence, were virtually reversed by reducing protein synthesis or blocking ERK of the MAP kinase family. These results suggest that cellular senescence is a manifestation of prolonged unbalanced growth linked with mechano transduction and can be prevented by at least two different ways.