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
bio-chemical 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.
