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

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 to understand how transcriptional changes relate to the process of aging and could serve as targets for future studies.

Availability: http://genomics.senescence.info/uarrays/signatures.html.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

Meta-signature of top genes consistently differentially expressed with age. (A) Genes consistently overexpressed with age. Fifteen datasets were selected for the figure. Red indicates genes overexpressed with age with the intensity proportional to the expression signal old/young adjusted for a common age (see Section 2). Black to gray indicates genes underexpressed with age. (B) Fourteen datasets were selected for the figure. Red indicates genes underexpressed with age with the intensity proportional to the expression signal young/old adjusted for a common age (see Section 2). Black to gray indicates genes overexpressed with age. For both A and B, white indicates either not studied or non-significant and genes are ordered from most to least significant.