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Modeling Premature Aging Syndromes with the Telomerase Knockout Mouse

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Understanding the molecular basis of the aging process is a daunting problem, given the complex genetic and physiological changes that underlie human aging and the lack of genetically amenable primate model systems. However, analysis of mouse models exhibiting aging phenotypes reminiscent of those observed in elderly humans has enhanced our understanding of the biological mechanisms underlying mammalian aging. In particular, these mouse models have brought to light the importance of the DNA damage pathway during the aging process. Increased genomic instability is associated with accelerated cellular decline and manifestation of premature aging phenotypes in mice. Here I discuss how one form of genomic instability, initiated by critically short telomeres in the telomerase knockout mouse, perturb normal mammalian aging. Insights into the molecular pathways of the aging process may offer unprecedented opportunities to delay the deleterious effects of the aging process.
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Keywords: chromosomal variants; cytogenetically; dna-damage; double strand breaks (dsbs); dyskeratosis; hematopoietic system; mammalian aging; metaphases; phenotypes; werner syndrome (ws)

Document Type: Review Article

Affiliations: Department of Molecular Genetics, MD Anderson Cancer Center, 1515 Holcombe Blvd. Houston, TX 77030, USA.

Publication date: March 1, 2005

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  • Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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