Activity Dependency and Aging in the Regulation of Adult Neurogenesis

Abstract

Age and activity might be considered the two antagonistic key regulators of adult neurogenesis. Adult neurogenesis decreases with age but remains present, albeit at a very low level, even in the oldest individuals. Activity, be it physical or cognitive, increases adult neurogenesis and thereby seems to counteract age effects. It is, thus, proposed that activity-dependent regulation of adult neurogenesis might contribute to some sort of "neural reserve," the brain's ability to compensate functional loss associated with aging or neurodegeneration. Activity can have nonspecific and specific effects on adult neurogenesis. Mechanistically, nonspecific stimuli that largely affect precursor cell stages might be related by the local microenvironment, whereas more specific, survival-promoting effects take place at later stages of neuronal development and require the synaptic integration of the new cell and its particular synaptic plasticity.

Figure 1.

Age effects on adult hippocampal neurogenesis. Even in the inaugural paper of the field, the original description by Altman and Das (1965) of adult hippocampal neurogenesis contained data revealing how strongly postnatal and adult neurogenesis decrease with age. Today, absolute numbers can be assigned to the different time points, revealing that, throughout most parts of the adult life, hippocampal neurogenesis ranges on a minute scale. (From Altman and Das 1965; reprinted, with kind permission, by Joseph Altman and John Wiley and Sons © 1965.)

Figure 2.

Different types of activity differently affect adult hippocampal neurogenesis. Whereas presumably nonspecific stimuli, such as physical activity, increase the proliferation of precursor cells in the dentate gyrus, presumably more specific stimuli like the exposure to a complex environment (environmental enrichment) preferentially increases the survival of newborn cells (the figure is a schematic rendering of data from Van Praag et al. 1999).