Neurogenesis in the Adult and Aging Brain

Excerpt

Given that neurogenesis is regionally restricted in the adult brain, the direct contribution of changes in neurogenesis to the development of aging-related cognitive decline is likely limited, perhaps accounting for the difficulty thus far in linking the decline in neurogenesis to specific neural deficits. As investigations of the contributions of adult neurogenesis to neural function continue, however, it is reasonable to expect they will demonstrate that the aging-related loss of the plasticity afforded by the continued addition of new neurons contributes to functional decline in senescence. Moreover, the interest of experimental gerontologists in the regulation of neurogenesis in the adult and aging brain extends beyond direct roles in hippocampal and olfactory function. It is reasonable to expect that the changes in neuronal microenvironment that lead to the decline in neurogenesis in older individuals may contribute to functional changes in established neurons and glial cells as well. In addition, the ability to isolate and expand neural stem cells from healthy brains, along with a rapidly growing capacity to regulate those cells and their progeny, keeps alive a vision of using transplanted stem cells to treat neurodegenerative diseases [216–221]. Even more appealing is that every advance in understanding the regulation of neurogenesis in vivo is a step toward therapeutic manipulation of endogenous progenitors to replace lost neurons or compensate for lost function [222], whether that occurring with normal aging or as a result of neurodegenerative disease. Although neuronal turnover is reduced in every neurogenic region of the aged brain, neuronal precursor cells clearly survive, remain responsive to growth factors and other physiological stimuli (e.g., [56, 58, 72, 81, 223]), and can increase their activity in response to damage (e.g., [63, 80]). Continued exploration of the regulation of neural progenitor cells in the adult and aging brain is critical not only for understanding normal, aging-related cognitive deficits, but also for progress toward the goal of using the brain’s regenerative potential to restore function lost to injury or neurodegenerative disease.