Jnk 介导的糖酵解激活导致精原干细胞衰老。
Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation.
机构信息
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, 606-8501 Kyoto, Japan;
Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (AMED-CREST), Chiyodaku, 100-0004 Tokyo, Japan.
出版信息
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16404-16409. doi: 10.1073/pnas.1904980116. Epub 2019 Jul 29.
Because spermatogonial stem cells (SSCs) are immortal by serial transplantation, SSC aging in intact testes is considered to be caused by a deteriorated microenvironment. Here, we report a cell-intrinsic mode of SSC aging by glycolysis activation. Using cultured SSCs, we found that aged SSCs proliferated more actively than young SSCs and showed enhanced glycolytic activity. Moreover, they remained euploid and exhibited stable androgenetic imprinting patterns with robust SSC activity despite having shortened telomeres. Aged SSCs showed increased expression, which was associated with decreased Polycomb complex 2 activity. Our results suggest that aberrant expression activated c- N-terminal kinase (JNK), which down-regulated mitochondria numbers by suppressing Down-regulation of probably decreased reactive oxygen species and enhanced glycolysis. Analyses of the -deficient aging mouse model and 2-y-old aged rats confirmed JNK hyperactivation and increased glycolysis. Therefore, not only microenvironment but also intrinsic activation of JNK-mediated glycolysis contributes to SSC aging.
由于精原干细胞（SSC）通过连续移植具有永生性，因此完整睾丸中的 SSC 衰老被认为是由微环境恶化引起的。在这里，我们报告了一种通过糖酵解激活的细胞内在的 SSC 衰老模式。使用培养的 SSC，我们发现衰老的 SSC 比年轻的 SSC 增殖更活跃，并且表现出增强的糖酵解活性。此外，尽管端粒缩短，它们仍保持着整倍体并表现出稳定的雄激素印迹模式和强大的 SSC 活性。衰老的 SSC 显示出 表达增加，这与多梳复合物 2 活性降低有关。我们的结果表明，异常的 表达激活了 c-氨基末端激酶（JNK），通过抑制 ，JNK 下调了线粒体数量。 下调可能会降低活性氧并增强糖酵解。对 -缺陷衰老小鼠模型和 2 岁老龄大鼠的分析证实了 JNK 的过度激活和糖酵解的增加。因此，不仅是微环境，JNK 介导的糖酵解的内在激活也会导致 SSC 衰老。
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