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Aging cells lose their grip on DNA rogues
Date:1/30/2013

ntial genes are located and closed "heterochromatin" formations around areas with active transposable elements and few desirable genes.

The distinction appeared to become worn in aging, or senescent, cells. In the observations, the chromatin that once was open tended to become more closed and the chromatin that was once closed, tended to become more open.

Working with computational biologist and Nicola Neretti, assistant professor of biology, Sedivy and De Cecco conducted a genome-wide analysis of these differences. The team extracted and then sequenced DNA from young and senescent human fibroblast cells using a technique called FAIRE. Essentially FAIRE uses chemicals such as formaldehyde to separate out DNA that is loosely packed in euchromatin from DNA that is more tightly wound up in heterochromatin.

Then the scientists compared the DNA that was coming from open or closed chromatin formations in the young and senescent cells.

"Given that our genomes contain well over a million copies of transposable elements and that they are very similar to one another, tracking all this mayhem is no easy matter," Neretti said. "Computationally speaking, it's a nightmare."

But Sedivy said results were well worth the effort. In their study not only did they find that the chromatin lockdown was breaking down, but also that the newly freed transposons were taking full advantage.

"I was really surprised to see that first of all these transposable elements start to get expressed and that they actually start moving around [to other regions in the genome]," Sedivy said. "That's really an amazing thing."

How bad and how to stop it?

What's not clear from the study is the relevance of the damage that the cells suffer from the transposable element jailbreak and resulting genetic crime spree. That depends on the timing, which Sedivy's team measured only in approximate terms.

"Is the transposition really bad for
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

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