Gene expression profiling with DNA microarrays can measure

Gene expression profiling of aging in multiple mouse
strains: identification of aging biomarkers and impact
of dietary antioxidants
Sang-Kyu Park,1, Kyoungmi Kim,2,Grier P. Page,2,
David B. Allison,2 Richard Weindruch3 and Tomas A.
1Department of Genetics and Medical Genetics, University of
Wisconsin, Madison, WI 53706, USA2Department of Biostatistics, Section on Statistical Genetics andClinical Nutrition Research Center, University of Alabama,Birmingham, AL 35294, USA3Department of Medicine and Wisconsin Primate ResearchCenter,VeteransAdministration Hospital, University of Wisconsin,Madison, WI 53706, USA

We used DNA microarrays to identify panels of transcriptional markers of aging that are differentially expressed in young (5 month) and old (25 month) mice of multiple inbred strains (129sv, BALB ⁄ c, CBA, DBA, B6, C3H and B6C3F1). In the heart, age-related changes of five genes were studied throughout the mouse lifespan: complement component 4, chemokine ligand 14, component of Sp100-rs, phenylalanine hydroxylase and src family associated phosphoprotein 2. A similar analysis in the brain (cerebellum) involved complement component 1q (alpha polypeptide), complement component 4, P lysozyme structural, glial fibrillary acidic protein and cathepsin S.Caloric restriction (CR) inhibited age-related expression of these genes in both tissues. Parametric analysis of gene set enrichment identified several biological processes that are induced with aging in multiple mouse strains. We also tested the ability of dietary antioxidants to oppose these transcriptional markers of aging. Lycopene, resveratrol, acetyl-L-carnitine and tempol were as effective as CR in the heart, and a-lipoic acid and coenzyme Q10 were as
effective as CR in the cerebellum. These findings suggest that transcriptional biomarkers of aging in mice can be used to estimate the efficacy of aging interventions on a tissue-specific basis. Key words: aging; antioxidants; biomarkers; caloricrestriction; microarray; mouse.

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