Learning from Werner Syndrome
Accelerated aging conditions may result from individual aspects of "normal" aging run wild and out of control. This means we can potentially learn more about those mechanisms. For example: "a gene shown to play a role in the aging process appears to play a role in the regulation of the differentiation of embryonic stem cells. ... researchers identified a protein interaction that controls the silencing of Oct4, a key transcription factor that is critical to ensuring that embryonic stem cells remain pluripotent. The protein, WRNp, is the product of a gene associated with Werner syndrome, an autosomal recessive disorder hallmarked by premature aging. ... We showed that the depletion of WRNp blocked the recruitment of Dnmt3b to the Oct4 promoter, and resulted in reduced methylation. The reduced DNA methylation was associated with continued Oct4 expression, which resulted in attenuated differentiation. ... These results reveal a novel function of WRNp, and demonstrate that WRNp controls a key step in pluripotent stem cell differentiation. Our data support the emerging hypothesis that attenuated stem cell differentiation is involved in aging. This lack of differentiated cells may contribute to failure to maintain organ or tissue function in the later stages of life."