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ABSTRACT 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 loss1. 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 microglia2. 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

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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Environmental

Toxicology Center, University of Wisconsin, Madison, Wisconsin, USA Cheol-Koo Lee * Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, Wisconsin, USA Cheol-Koo

Lee & Tomas A. Prolla * Department of Medicine and Wisconsin Regional Primate Research Center, University of Wisconsin, and Veterans Administration Hospital, Geriatric Research,

Education and Clinical Center, Madison, Wisconsin, USA Richard Weindruch Authors * Cheol-Koo Lee View author publications You can also search for this author inPubMed Google Scholar *

Richard Weindruch View author publications You can also search for this author inPubMed Google Scholar * Tomas A. Prolla View author publications You can also search for this author inPubMed

 Google Scholar CORRESPONDING AUTHORS Correspondence to Richard Weindruch or Tomas A. Prolla. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lee, CK.,

Weindruch, R. & Prolla, T. Gene-expression profile of the ageing brain in mice. _Nat Genet_ 25, 294–297 (2000). https://doi.org/10.1038/77046 Download citation * Received: 17 November

1999 * Accepted: 12 April 2000 * Issue Date: July 2000 * DOI: https://doi.org/10.1038/77046 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

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