Introduction

Until recently, Werner syndrome (WS) had been considered to be a model of accelerated aging. The Werner gene (WRN) was identified in 1996 (1) and was subsequently shown to act as a DNA helicase and as an exonuclease (2,3). Since then, cancer researchers and those who study DNA metabolism have collaborated to further characterize WS and the function of the WRN gene. The more we understand about the WRN gene, the more we realize that WS is not merely accelerated aging. WS certainly does not represent premature aging, in the sense that the characteristic aging phenotypes seen in WS are considerably different from those observed in normal older adults. WS is now being more correctly recognized as a condition in which the lack of WRN protein (WRNp) results in an overall decline in the normal physiological functions of various organs, including those most frequently used to estimate chronological age (e.g., skin and hair).

Since the identification of the WRN gene, various in vitro biochemical studies of WRNp have answered many of our initial questions regarding the helicase and exonuclease functions of this enzyme. Considerably more time will be required to answer the more difficult questions concerning the in vivo functions of WRN at the cellular and organismal levels. The lack of WS mouse models that mimic the human disorder currently limits our ability to carry out such studies. In this chapter, the known in vitro functions of WRNp and the cellular characteristics of WS cells will be summarized. From this, the putative in vivo functions of WRN will be extrapolated.

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