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 w hen obtaining areal densities. These new techniques are rapidly becoming th e standard for quantifying cell number, particularly in aging studies. Rece ntly, 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 biogerontolo gy, prompting revaluation of long-standing hypotheses of age-related cell l oss as causal for age-related impairments ill brain functioning. Rather tha n focus on neuronal loss as the end-result of a negative cascade of neurona l injury, research has begun to consider that age-related behavioral declin es may reflect neuronal dysfunction (e.g., synaptic or receptor loss, signa l 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. Emerge nce of this method of morphometrics, however, can have relevance to many ar eas of gerontological research.