The brain's fight against aging

International audienceA lterations of sensorial and cog-nitive performance appear with aging and affect quality of life. This is becoming an important societal and public health issue in our aging populations. The increasing number of elderly people in our society with their associated pathologies creates a need for better understanding of how the aged brain is different from the young brain. Surprisingly, very little is known about the cellular correlates of normal aging in the brain. Insights into structural alterations are essential to understanding the functional and cognitive changes associated with aging. In PNAS, Richard et al. (1), using the olfactory bulb (OB) as a simplified cortical model, show the overall stability of the structure and indicate that there is no neurodegeneration with aging. Interestingly, the results reveal fine syn-aptic alterations that affect selected cellular compartments, thereby opening perspectives for understanding the mechanisms of aging at the level of the cortical subcircuits. These data refute the view of aging as nonspecific homogeneous and regressive events and promote the view that more subtle alterations of brain circuitry could account for age-related functional changes. The OB is an appropriate model for studying the effect of aging for several reasons. First, this sensory cortex has a well-known synaptic organization (2, 3). Second, olfaction is altered in normal (4-9) and pathological aging (10, 11), leading to food intake impairment, reduced quality of life, and altered health in the elderly. In addition , given the functional importance of ol-faction in rodents and the similarities between the organization of the human and rodent olfactory systems, the mouse OB is relevant for studying aging in the brain. Overall Stability of the OB A key finding of this study is that the anatomical features of the OB from its lam-inar organization to its cell numbers are strikingly stable in C57Bl6J mice. Indeed, using classical stereological methods associated with specific immunohistological staining of cell subpopulations, the authors find that the total volume of both the OB and its individual layers and the number of interneurons (granule and peri-glomerular cells) and relay cells (mitral cells) do not change across life. This finding is interesting with regard to the permanent supply of neurons, thanks to the process of adult neurogenesis targeting both olfactory sensory neurons projecting from the olfactory epithelium to the OB and bulbar interneurons. Indeed, neuro-genesis is known to dramatically decrease with aging (4, 12), and furthermore, ab-lation of bulbar neurogenesis has been shown to induce a reduction in the granule cell volume of the adult OB (13). One could thus expect that the volume of the OB and number of interneurons would decrease with aging. The structural stability of the OB shown by Richard et al. (1) is important in that it indicates that strong Richard et al. find that specific subsets of synapses are affected by aging