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Salk Institute Scientists Discover How Gene Mutations Can Cause Premature Ageing

by Bidita Debnath on May 2, 2015 at 8:20 PM
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Salk Institute Scientists Discover How Gene Mutations Can Cause Premature Ageing

For the first time, a team of scientists at Salk Institute have created a key class of versatile stem cells that carry the genetic defect that causes premature aging.

The study found that the genetic mutations underlying Werner syndrome, a disorder that leads to premature aging and death, resulted in the deterioration of bundles of DNA known as heterochromatin.

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Juan Carlos Izpisua Belmonte, a senior author on the paper asserted that their findings showed that the gene mutation that caused Werner syndrome resulted in the disorganization of heterochromatin, and that this disruption of normal DNA packaging was a key driver of aging.

Werner syndrome is a genetic disorder that causes people to age more rapidly than normal. It affects around one in every 200,000 people in the United States. People with the disorder suffer age-related diseases early in life, including cataracts, type 2 diabetes, hardening of the arteries, osteoporosis and cancer, and most die in their late 40s or early 50s.
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In their study, the Salk scientists sought to determine precisely how the mutated WRN protein causes so much cellular mayhem. To do this, they created a cellular model of Werner syndrome by using a cutting-edge gene-editing technology to delete WRN gene in human stem cells.

This stem cell model of the disease gave the scientists the unprecedented ability to study rapidly aging cells in the laboratory. The resulting cells mimicked the genetic mutation seen in actual Werner syndrome patients, so the cells began to age more rapidly than normal. On closer examination, the scientists found that the deletion of the WRN gene also led to disruptions to the structure of heterochromatin, the tightly packed DNA found in a cell's nucleus.

Belmonte said that their study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation.

Source: ANI
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