Mutations in the chromosome 8p WRN gene cause Werner syndrome (WRN), a human autosomal recessive disease that mimics premature aging and is associated with genetic instability and an increased risk of cancer.
This mouse model thus provides a unique genetic platform to explore molecular mechanisms by which telomere dysfunction and loss of WRN gene function leads to the onset of premature aging and cancer.
Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types.
Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature ageing and cancer predisposition.
Naturally occurring mutations in the human RECQ3 gene result in truncated Werner protein (WRN) and manifest as a rare premature aging disorder, Werner syndrome.
Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer.
Here, we report that NDH II interacts with the Werner syndrome helicase WRN, an enzyme associated with premature aging and predisposition to tumorigenesis.
BLM and WRN are also human RecQ helicases, which are mutated in Bloom and Werner's syndrome, respectively, and associated with chromosomal instability as well as premature aging.
Five members of the RecQ subfamily of DEx-H-containing DNA helicases have been identified in both human and mouse, and mutations in BLM, WRN, and RECQ4 are associated with human diseases of premature aging, cancer, and chromosomal instability.
WRN-1 is the Caenorhabditis elegans homolog of the human Werner syndrome protein, a RecQ helicase, mutations of which are associated with premature aging and increased genome instability.
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.
These include the human BLM gene, whose mutation results in Bloom syndrome, and the human WRN gene, whose mutation leads to Werner syndrome resembling premature aging.
The induced pluripotent stem cell (iPSC) technology has provided a unique opportunity to develop disease-specific models and personalized treatment for genetic disorders, and is well suitable for the study of Werner syndrome (WS), an autosomal recessive disease with adult onset of premature aging caused by mutations in the RecQ like helicase (WRN) gene.
Although WS has been characterized by a variety of clinical manifestations mimicking premature aging, the recent longevity and delayed age-associated manifestations observed both from Japanese WS and general population may suggest a common environmental effect on some gene(s) other than WRN and may give us a newer pathophysiological look at WS and also natural aging through the molecular dysfunction of WRN.
Future research should focus on the mechanism(s) of WRN in the regulation of the various DNA metabolism pathways and development of therapeutic approaches to treat premature aging syndromes such as WS.
Mutations in the RecQ helicases BLM and WRN are linked to the cancer-prone disorder Bloom's syndrome and premature aging condition Werner syndrome, respectively.
Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin.