• Open Access

Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants

Authors

  • Sang-Kyu Park,

    1. Department of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
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    • *

      Present addresses: Institute for Behavioral Genetics, University of Colorado at Boulder, 1480 30th St, Boulder, CO 80303, USA.

  • Kyoungmi Kim,

    1. Department of Biostatistics, Section on Statistical Genetics and Clinical Nutrition Research Center, University of Alabama, Birmingham, AL 35294, USA
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    • Division of Biostatistics, Department of Public Health Sciences, UC Davis School of Medicine, Davis 95616, CA, USA.

  • Grier P. Page,

    1. Department of Biostatistics, Section on Statistical Genetics and Clinical Nutrition Research Center, University of Alabama, Birmingham, AL 35294, USA
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    • Statistics and Epidemiology RTI International, Atlanta, GA 30341, USA.

  • David B. Allison,

    1. Department of Biostatistics, Section on Statistical Genetics and Clinical Nutrition Research Center, University of Alabama, Birmingham, AL 35294, USA
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  • Richard Weindruch,

    1. Department of Medicine and Wisconsin Primate Research Center, Veterans Administration Hospital, University of Wisconsin, Madison, WI 53706, USA
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  • Tomas A. Prolla

    1. Department of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
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Tomas A. Prolla, 5302B Genetics/Biotechnology building, 425 Henry Mall, Madison, WI 53706, USA. Tel.: (608) 265 5204; fax: (608) 262 2976; e-mail: taprolla@wisc.edu

Summary

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 α-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.

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