A cascade leading to premature aging phenotypes including abnormal tumor profiles in Werner syndrome (review).

[werner syndrome]

This perspective review focused on the Werner syndrome (WS ) by addressing the issue of how a single mutation in a WRN gene encoding WRN DNA helicase induces a wide range of premature aging phenotypes accompanied by an abnormal pattern of tumors . The key event caused by WRN gene mutation is the dysfunction of telomeres . Studies on normal aging have identified a molecular circuit in which the dysfunction of telomeres caused by cellular aging activates the TP 53 gene . The resultant p 53 suppresses cell growth and induces a shorter cellular lifespan , and also compromises mitochondrial biogenesis leading to the overproduction of reactive oxygen species (ROS ) causing multiple aging phenotypes . As an analogy of the mechanism in natural aging , we described a hypothetical mechanism of premature aging in WS : telomere dysfunction induced by WRN mutation causes multiple premature aging phenotypes of WS , including shortened cellular lifespan and inflammation induced by ROS , such as diabetes mellitus . This model also explains the relatively late onset of the disorder , at approximately age 20 . Telomere dysfunction in WS is closely correlated with abnormality in tumorigenesis . Thus , the majority of wide and complex pathological phenotypes of WS may be explained in a unified manner by the cascade beginning with telomere dysfunction initiated by WRN gene mutation .

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Diseases presenting "complex pathological phenotypes" symptom

werner syndrome

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