Aging and neurogenesis in the adult forebrain: what we have learned and where we should go from here

• Published in: The European journal of neuroscience 2013-06, Vol.37 (12), p.1978-1986
• Main Authors: Hamilton, Laura K., Joppé, Sandra E., M. Cochard, Loїc, Fernandes, Karl J. L.
• Format: Article
• Language: English
• Subjects: Aging - physiology; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Lateral Ventricles - cytology; Mice; neural stem cells; Neural Stem Cells - cytology; Neurogenesis - physiology; neurospheres; Prosencephalon - cytology; quiescence; Rats; rodent; senescence
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12207

In the brains of adult vertebrates, including humans, neurogenesis occurs in restricted niches where it maintains cellular turnover and cognitive plasticity. In virtually all species, however, aging is associated with a significant decline in adult neurogenesis. Moreover, an acceleration of neurogenic defects is observed in models of Alzheimer's disease and other neurodegenerative diseases, suggesting an involvement in aging‐ and disease‐associated cognitive deficits. To gain insights into when, how and why adult neurogenesis decreases in the aging brain, we critically reviewed the scientific literature on aging of the rodent subventricular zone, the neurogenic niche of the adult forebrain. Our analysis revealed that deficits in the neurogenic pathway are largely established by middle age, but that there remains striking ambiguity in the underlying mechanisms, especially at the level of stem and progenitor cells. We identify and discuss several challenging issues that have contributed to these key gaps in our current knowledge. In the future, addressing these issues should help untangle the interactions between neurogenesis, aging and aging‐associated diseases. To understand when, how and why adult neurogenesis decreases in the aging brain, we critically reviewed the scientific literature on aging of the rodent subventricular zone, the neurogenic niche of the forebrain. Our analysis revealed that deficits in the neurogenic pathway occur by middle‐age, but that there remains striking ambiguity in the underlying mechanisms, especially at the level of stem and progenitor cells. We discuss several issues that have led to these gaps in our knowledge.