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Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging
Lee, J., W. O. Ward, G. Michael, H. Ren, B. Vallanat, G. Darlington, S. Han, J. C. Laguna, J. DeFord, J. Papaconstantinou, C. Selman, AND C. CORTON. Meta-analysis of Gene Expression in the Mouse Liver Reveals Biomarkers Associated with Inflammation Increased Early During Aging. MECHANISMS OF AGEING AND DEVELOPMENT. Elsevier Science Ltd, New York, NY, 133(7):467-78, (2012).
This meta-analysis identified a number of genes whose expression is consistently altered in the livers of aging mice, associated with TLN.
Aging is associated with a predictable loss of cellular homeostasis, a decline in physiological function and an increase in various diseases. We hypothesized that similar age-related gene expression profiles would be observed in mice across independent studies. Employing a metaanalysis, whole-genome hepatic gene expression profiles from four independent mouse aging studies were interrogated. Contrary to our hypothesis, there was surprisingly little overlap across studies in the number of genes or canonical pathways perturbed, suggesting that independent study-specific factors, such as housing, diet or background strain, may playa significant role in determining age dependent gene expression. However, 43 genes were consistently altered during aging in three or all of these studies. These included those that 1) xhibited progressively increased expression starting from 12 months of age, 2) exhibited similar expression changes in models of progeria at young ages and dampened or no changes in old long-lived mouse models, 3) were associated with inflammatory tertiary lymphoid neogenesis (TLN) entailing formation of ectopic lymphoid structures observed in chronically inflamed tissues, and 4) overlapped with genes perturbed by aging in brain, muscle and lung, but not heart. Surprisingly, around half of the genes altered by aging in wild-type mice exhibited similar expression in adult long-lived mice compared to wild-type controls, including those associated with intermediary metabolism and feminization of the male-dependent gene expression pattern. Genes unique to aging in wild-type mice included those linked to TLN. This meta-analysis identified a number of genes whose expression is consistently altered in the livers of aging mice, associated with TLN. We suggest these genes are useful biomarkers of aging in mice and could be employed to test the effectiveness of potential lifespan and healthspan extending interventions
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH