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Genomic Instability in Human Premature Aging

  • Chapter
Aging at the Molecular Level

Part of the book series: Biology of Aging and Its Modulation ((BIMO,volume 1))

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Abstract

A number of premature aging disorders have been described in humans. In patients with these disorders, aging-like symptoms and age-associated diseases appear much earlier than in the average normal individual; thus, the premature aging disorders are useful models for the study of the aging process (Figure 1). Werner syndrome (WS) is the most characterized premature aging disorder. Patients with WS have a large number of signs and symptoms of normal aging at a younger age than normal individuals. However, not all symptoms of WS resemble the normal aging process, and WS is best described as a segmental progeroid disorder. The premature aging disorders include the DNA repair defective disease, xeroderma pigmentosum (XP), which includes seven complementation groups (separate genetic disorders). In this condition, the deficiency of the DNA repair pathway, nucleotide excision, leads to a severely increased incidence of cancer. In Cockayne syndrome, there is also a DNA repair defect, and in addition to the features of premature aging, these individuals have severe neurological deficits. Rothmund-Thomson disease, Hutchinson-Guilford and progeria are other examples of this category of disorders. All of these diseases are very rare conditions in the general population. In several cases, the disorders are associated with a mutation in a single gene, which has by now been identified, cloned and characterized. This means that molecular biochemical experimentation can be done. Complementation assays with transfected mutant cell lines or purified proteins added to extracts from mutant cell lines can be used to study the basis of molecular genetic defects (Figure 1).

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Author information

Authors and Affiliations

  1. Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Vilhelm A. Bohr & Patricia L. Opresko

Authors
  1. Vilhelm A. Bohr
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  2. Patricia L. Opresko
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Editors and Affiliations

  1. Henry Wellcome Laboratory for Biogerontology, Newcastle General Hospital, University of Newcastle, Newcastle upon Tyne, UK

    Thomas von Zglinicki (Professor of Cellular Gerontology) (Professor of Cellular Gerontology)

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© 2003 Springer Science+Business Media Dordrecht

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Bohr, V.A., Opresko, P.L. (2003). Genomic Instability in Human Premature Aging. In: von Zglinicki, T. (eds) Aging at the Molecular Level. Biology of Aging and Its Modulation, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0667-4_5

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  • DOI: https://doi.org/10.1007/978-94-017-0667-4_5

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-6482-0

  • Online ISBN: 978-94-017-0667-4

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