The brain's fight against aging

Numerous studies have documented diminution in sensory and cognitive functions with aging, but very little is known about what is actually happening to cells in the brain. Knowing more about structural alterations as the brain ages is essential to understanding functional and cognitive changes. Richard et al.have used a simplified cortical model, the olfactory bulb in the mouse brain, to show, somewhat surprisingly, overall stability of structure and no neurodegeneration with aging. What they do observe is fine synaptic alterations that affect selected cellular compartments, and losses of synapses in specific layers. (The olfactory bulb sensory cortex is an appropriate model because it has well-known synaptic organization, and its normal and pathological aging is associated with impairment of food intake and reduced health.)

Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region- and layer-specific alterations of neuron morphology and synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse. To assess the effect of aging on the organization of olfactory bulb (OB) circuitry, we carried out quantitative morphometric analyses in the mouse OB at 2, 6, 12, 18, and 24 mo. Our data establish that the volumes of the major OB layers do not change during aging. Parallel to this, we are unique in demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide unique evidence of the stability of projection neurons and interneurons subpopulations in the aging mouse OB, arguing against the notion of an age-dependent widespread loss of neurons. Finally, we show ultrastructurally a significant layer-specific loss of synapses; synaptic density is reduced in the glomerular layer but not the external plexiform layer, leading to an imbalance in OB circuitry. These results suggest that reduction of afferent synaptic input and local modulatory circuit synapses in OB glomeruli may contribute to specific age-related alterations of the olfactory function.