Tissue-Specific Stem Cells
Article first published online: 16 NOV 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 12, pages 2005–2017, December 2011
How to Cite
Stoll, E. A., Habibi, B. A., Mikheev, A. M., Lasiene, J., Massey, S. C., Swanson, K. R., Rostomily, R. C. and Horner, P. J. (2011), Increased Re-Entry into Cell Cycle Mitigates Age-Related Neurogenic Decline in the Murine Subventricular Zone. STEM CELLS, 29: 2005–2017. doi: 10.1002/stem.747
Author contributions: E.A.S.: conception and design, collection and/or assembly of data, data analysis and interpretation, development of mathematical model, and manuscript writing; B.A.H.: collection and/or assembly of data and data analysis and interpretation; A.M.M.: conception and design; J.L.: collection and/or assembly of data; S.C.M. and K.R.S.: development of mathematical model; R.C.R. and P.J.H.: conception and design, financial support, data analysis and interpretation, and manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS September 10, 2011.
- Issue published online: 16 NOV 2011
- Article first published online: 16 NOV 2011
- Accepted manuscript online: 21 SEP 2011 01:14PM EST
- Manuscript Accepted: 10 SEP 2011
- Manuscript Received: 19 JAN 2011
- University of Washington Training
- Developmental Biology. Grant Number: HDO7183-28
- University of Washington Retirement Association Fellowship
- American Foundation for Aging Research
- Mary Gates Undergraduate Fellowship. Grant Numbers: AG029406, NSO46724
- Mitotic rate;
- Mitotic activity;
Although new neurons are produced in the subventricular zone (SVZ) of the adult mammalian brain, fewer functional neurons are produced with increasing age. The age-related decline in neurogenesis has been attributed to a decreased pool of neural progenitor cells (NPCs), an increased rate of cell death, and an inability to undergo neuronal differentiation and develop functional synapses. The time between mitotic events has also been hypothesized to increase with age, but this has not been directly investigated. Studying primary-cultured NPCs from the young adult and aged mouse forebrain, we observe that fewer aged cells are dividing at a given time; however, the mitotic cells in aged cultures divide more frequently than mitotic cells in young cultures during a 48-hour period of live-cell time-lapse imaging. Double-thymidine-analog labeling also demonstrates that fewer aged cells are dividing at a given time, but those that do divide are significantly more likely to re-enter the cell cycle within a day, both in vitro and in vivo. Meanwhile, we observed that cellular survival is impaired in aged cultures. Using our live-cell imaging data, we developed a mathematical model describing cell cycle kinetics to predict the growth curves of cells over time in vitro and the labeling index over time in vivo. Together, these data surprisingly suggest that progenitor cells remaining in the aged SVZ are highly proliferative. STEM CELLS 2011;29:2005–2017.