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Bioinformatics Advance Access published online on February 2, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp073
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Meta-analysis of age-related gene expression profiles identifies common signatures of aging

João Pedro de Magalhães 1,*,{dagger}, João Curado 2 and George M. Church 1

1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
2Escola Superior de Biotecnologia, 4200 Porto, Portugal

*To whom correspondence should be addressed. Dr. Joao Pedro de Magalhaes, E-mail: jp{at}senescence.info


  Abstract

Motivation: Numerous microarray studies of aging have been conducted, yet given the noisy nature of gene expression changes with age, elucidating the transcriptional features of aging and how these relate to physiological, biochemical, and pathological changes remains a critical problem.

Results: We performed a meta-analysis of age-related gene expression profiles using 27 datasets from mice, rats, and humans. Our results reveal several common signatures of aging, including 56 genes consistently overexpressed with age, the most significant of which was APOD, and 17 genes underexpressed with age. We characterized the biological processes associated with these signatures and found that age-related gene expression changes most notably involve an overexpression of inflammation and immune response genes and of genes associated with the lysosome. An underexpression of collagen genes and of genes associated with energy metabolism, particularly mitochondrial genes, as well as alterations in the expression of genes related to apoptosis, cell cycle, and cellular senescence biomarkers, were also observed. By employing a new method that emphasizes sensitivity, our work further reveals previously unknown transcriptional changes with age in many genes, processes, and functions. We suggest these molecular signatures reflect a combination of degenerative processes but also transcriptional responses to the process of aging. Overall, our results help understand how transcriptional changes relate to the process of aging and could serve as targets for future studies.

Contact: jp{at}senescence.info

Supplementary information: Supplementary data are available at http://genomics.senescence.info/uarrays/signatures.html

{dagger}Present address: School of Biological Sciences, University of Liverpool, Biosciences Building, Crown St., Liverpool L69 7ZB, UK.

Associate Editor: Prof. David Rocke

Received on September 15, 2008; revised on January 11, 2009; accepted on January 31, 2009

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