Non-monotonic changes in Progenitor Cell Behavior and Gene expression during aging of the Adult Neural Stem Cell Niche

Neural stem cell activity in the ventricular-subventricular zone (V-SVZ) decreases with aging, thought to occur by a unidirectional decline. However, by analyzing the V-SVZ transcriptome of male mice at 2, 6, 18 and 22 months, we found that most of the genes that change significantly over time show a reversal of trend, with a maximum or minimum expression at 18 months. In vivo, MASH1+ progenitor cells decrease in number and proliferation between 2-18 months, but these increased between 18-22 months. Time-lapse lineage analysis of 944 V-SVZ cells showed that age-related declines in neurogenesis were recapitulated in vitro in clones. However, activated type B/type C cell clones divide slower from 2-18 months, then unexpectedly faster at 22 months, with impaired transition to type A neuroblasts. Our findings indicate that aging of the V-SVZ involves significant non-monotonic changes that are programed within progenitor cells, and observable independent of the aging niche. RNA extracted from Mouse SVZ, in triplicate, from ages 2, 6, 18 and 22 months.