Quiescence modulates stem cell maintenance and regenerative capacity in the aging brain

Authors: Georgios Kalamakis, Daniel Brüne, Srikanth Ravichandran, Jan Bolz, Wenqiang Fan, Frederik Ziebell, Thomas Stiehl, Francisco Catalá-Martinez, Janina Kupke, Sheng Zhao, Enric Llorens-Bobadilla, Katharina Bauer, Stefanie Limpert, Birgit Berger, Urs Christen, Peter Schmezer, Jan Philipp Mallm, Benedikt Berninger, Simon Anders, Antonio del Sol, Anna Marciniak-Czochra, Ana Martin-Villalba


The function of somatic stem cells declines with age. Understanding the molecularunderpinnings of this decline is key to counteract age-related disease. Here, we reporta dramatic drop in the neural stem cells (NSCs) number in the aging murine brain. Wefind that this smaller stem cell reservoir is protected from full depletion by anincrease in quiescence that makes old NSCs more resistant to regenerate the injuredbrain. Once activated, however, young and old NSCs show similar proliferation anddifferentiation capacity. Single-cell transcriptomics of NSCs indicate that agingchanges NSCs minimally. In the aging brain, niche-derived inflammatory signals andthe Wnt antagonist sFRP5 induce quiescence. Indeed, intervention to neutralize themincreases activation of old NSCs during homeostasis and following injury. Our studyidentifies quiescence as a key feature of old NSCs imposed by the niche and uncoversways to activate NSCs to repair the aging brain.

Source: Cell, 2019