TY - JOUR
T1 - Gene-expression profile of the ageing brain in mice
AU - Lee, Cheol Koo
AU - Weindruch, Richard
AU - Prolla, Tomas A.
N1 - Funding Information:
This work was supported by NIH grants P01 AG11915 (R.W.) and R01 CA 78723 (T.A.P.). T.A.P. is a recipient of the Shaw Scientist (Milwaukee Foundation), Burroughs Wellcome Young Investigator and Basil O’Connor (March of Dimes) awards.
PY - 2000/7
Y1 - 2000/7
N2 - 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 functional alterations in specific neuronal circuits, as opposed to large- scale neuronal loss. In fact, ageing of the central nervous system in diverse mammalian 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 and microglia. To provide the first global analysis of brain ageing at the molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. At the transcriptional level, brain ageing in mice displays parallels with human neurodegenerative disorders. Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses.
AB - 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 functional alterations in specific neuronal circuits, as opposed to large- scale neuronal loss. In fact, ageing of the central nervous system in diverse mammalian 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 and microglia. To provide the first global analysis of brain ageing at the molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. At the transcriptional level, brain ageing in mice displays parallels with human neurodegenerative disorders. Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses.
UR - http://www.scopus.com/inward/record.url?scp=0000847978&partnerID=8YFLogxK
U2 - 10.1038/77046
DO - 10.1038/77046
M3 - Article
C2 - 10888876
AN - SCOPUS:0000847978
SN - 1061-4036
VL - 25
SP - 294
EP - 297
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -