The Werner syndrome. A model for the study of human aging.
Human aging is a complex process that leads to the gradual deterioration of body functions with time. Various models to approach the study of aging have been launched over the years such as the genetic analysis of life span in the yeast S. cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human models, there have been extensive efforts using replicative senescence, the study of centenerians, comparisons of young versus old at the organismal, cellular, and molecular levels, and the study of premature aging syndromes to understand the mechanisms leading to aging. One good model for studying human aging is a rare autosomal recessive disorder known as the Werner syndrome (WS), which is characterized by accelerated aging in vivo and in vitro. A genetic defect implicated in WS was mapped to the WRN locus. Mutations in this gene are believed to be associated, early in adulthood, with clinical symptoms normally found in old individuals. WRN functions as a DNA helicase, and recent evidence, summarized in this review, suggests specific biochemical roles for this multifaceted protein. The interaction of WRN protein with RPA (replication protein A) and p53 will undoubtedly direct efforts to further dissect the genetic pathway(s) in which WRN protein functions in DNA metabolism and will help to unravel its contribution to the human aging process.
Laboratory of Molecular Gerontology and Dermatology, Copenhagen University Hospital, Denmark. nehlinj@rh.dk
J O
JO
Nehlin
G L
GL
Skovgaard
V A
VA
Bohr
D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005090:Exodeoxyribonucleases; D005544:Forecasting; D006801:Humans; D051379:Mice; D008954:Models, Biological; D053484:RecQ Helicases; D051716:Replication Protein A; D013347:Subcellular Fractions; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000071657:Werner Syndrome Helicase
D004268:DNA-Binding Proteins; C497167:RPA1 protein, human; D051716:Replication Protein A; C497168:Rpa1 protein, mouse; D016159:Tumor Suppressor Protein p53; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase