What counts in brain aging? Design-based stereological analysis of cell number

The advent and implementation of new design-based stereological techniques allows the quantification of cell number without the assumptions required when obtaining areal densities. These new techniques are rapidly becoming the standard for quantifying cell number, particularly in aging studies. Recently, studies using stereological techniques have failed to confirm earlier findings regarding age-associated neural loss. This newly emerging view of retained cell number during aging is having a major impact on biogerontology, prompting revaluation of long-standing hypotheses of age-related cell loss as causal for age-related impairments in brain functioning. Rather than focus on neuronal loss as the end-result of a negative cascade of neuronal injury, research has begun to consider that age-related behavioral declines may reflect neuronal dysfunction (e.g., synaptic or receptor loss, signal transduction deficits) instead of neuronal death. Here we discuss design-based stereology in the context of age-related change in brain cell number and its impact on consideration of structural change in brain aging. Emergence of this method of morphometrics, however, can have relevance to many areas of gerontological research.