Gene-expression profile of the ageing brain in mice

Ageing of the brain leads to impairments in cognitive and motor skills, and is the major risk factor for several common neurological disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Recent studies suggest that normal brain ageing is associated with subtle morphological and functi onal alterations in specific neuronal circuits, as opposed to large-scale n euronal loss'. In fact, ageing of the central nervous system in diverse mam malian species shares many features, such as atrophy of pyramidal neurons, synaptic atrophy, decrease of striatal dopamine receptors. accumulation of fluorescent pigments, cytoskeletal abnormalities, and reactive astrocytes a nd microglia(2). To provide the first global analysis of brain ageing at th e molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebe llum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support i n both brain regions. At the transcriptional level, brain ageing in mice di splays parallels with human neurodegenerative disorders. Caloric restrictio n, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress response s.