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Reciprocal phylogenetic conservation of molecular aging in mouse and human brain.

ABSTRACT: Studies of age-related molecular profiles have separately focused on the human and rodent brains, but the extent to which each organism predicts molecular events across species for the global signature of aging and for specific biological functions has only begun to be characterized. We previously showed that the molecular correlates of aging in the mouse cortex moderately, but significantly, predicted transcript changes in human frontal cortex. Using orthologous gene links between large-scale gene expression datasets, we now report a similar reciprocal human-to-mouse prediction of molecular aging in frontal cortex, but a limited and variable conservation of age-effects across a wide spectrum of biological functions. Thus, the moderate transcriptome correlations and partial functional concordance between late-life human and rodent cohorts (13-77 years in humans and 3-24 months in mice) suggest limitations of the mouse to model normal aging of the human brain cortex.

SUBMITTER: Oh S

PROVIDER: S-EPMC2888783 | biostudies-other | 2011 Jul

REPOSITORIES: biostudies-other

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Reciprocal phylogenetic conservation of molecular aging in mouse and human brain.

Oh Sunghee S Tseng George C GC Sibille Etienne E

Neurobiology of aging 20090902 7

Studies of age-related molecular profiles have separately focused on the human and rodent brains, but the extent to which each organism predicts molecular events across species for the global signature of aging and for specific biological functions has only begun to be characterized. We previously showed that the molecular correlates of aging in the mouse cortex moderately, but significantly, predicted transcript changes in human frontal cortex. Using orthologous gene links between large-scale g ...[more]

PMID: 19729224

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Project description:Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.

Dataset Information

Reciprocal phylogenetic conservation of molecular aging in mouse and human brain.

Publications

Reciprocal phylogenetic conservation of molecular aging in mouse and human brain.

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