Aging of mouse spermatogonial stem cells by Wnt7b-Jnk pathway activation. Mus musculus

Although spermatogonial stem cells (SSCs) are thought to be virtually immortal, the number of SSCs declines during aging, which is considered to be induced by deterioration of microenvironment. Here we report that cell-intrinsic mode of SSC aging. SSCs cultured for 5 years proliferate more actively than young SSCs and showed enhanced glycolytic activity but remain euploid and exhibit stable androgenetic imprinting patterns. Moreover, the aged SSCs kept constant SSC activity despite shortened telomeres. The increased proliferative activity of aged SSCs was caused by Wnt7b expression, which likely occurred due to decreased polycomb complex2 activity. Aberrant Wnt7b expression not only decreased reactive oxygen species levels and mitochondria activity but also stimulated glycolysis via JNK activation. Analysis of SSCs in Klotho aging mouse model also confirmed hyperactivation of JNK pathway and increased glycolysis. Therefore, not only SSC microenvironment but also intrinsic activation of Wnt7b-mediated glycolysis plays important roles in SSC aging.