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Aging and Genome Maintenance

Authors

  • JAN VIJG,

    Corresponding author
    1. University of Texas Health Science Center, San Antonio, Texas 78245, USA
    2. Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA
      Address for correspondence: Professor Jan Vijg, University of Texas Health Science Center, STCBM, 15355 Lambda Drive, Suite 2.200, San Antonio, TX 78245. Voice: 210-562-5027; fax: 210-562-5028; E-mail: vijg@uthscsa.edu
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  • RITA A. BUSUTTIL,

    1. University of Texas Health Science Center, San Antonio, Texas 78245, USA
    2. Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA
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  • RUMANA BAHAR,

    1. University of Texas Health Science Center, San Antonio, Texas 78245, USA
    2. Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA
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  • MARTIJN E.T. DOLLÉ

    1. University of Texas Health Science Center, San Antonio, Texas 78245, USA
    2. Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA
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Address for correspondence: Professor Jan Vijg, University of Texas Health Science Center, STCBM, 15355 Lambda Drive, Suite 2.200, San Antonio, TX 78245. Voice: 210-562-5027; fax: 210-562-5028; E-mail: vijg@uthscsa.edu

Abstract

Genomic instability in somatic cells has been implicated as a major stochastic mechanism of aging. Using a transgenic mouse model with chromosomally integrated lacZ mutational target genes, we found mutations to accumulate with age at an organ- and tissue-specific rate. Also the spectrum of age-accumulated mutations was found to differ greatly from organ to organ; while initially similar, mutation spectra of different tissues diverged significantly over the lifetime. To explain how genomic instability, which is inherently stochastic, can be a causal factor in aging, it is proposed that randomly induced mutations may adversely affect normal patterns of gene regulation, resulting in a mosaic of cells at various stages on a trajectory of degeneration, eventually resulting in cell death or neoplastic transformation. To directly address this question we demonstrate that it is now possible to analyze single cells, isolated from old and young tissues, for specific alterations in gene expression.

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