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Ticking of cellular clock promotes seismic changes in the chromatin landscape associated with aging
Date:10/3/2010

LA JOLLA, CA-Like cats, human cells have a finite number of lives-once they divide a certain number of times (thankfully, more than nine) they change shape, slow their pace, and eventually stop dividing, a phenomenon called "cellular senescence".

Biologists know that a cellular clock composed of structures at the chromosome end known as telomeres records how many "lives" a cell has expended. Up to now, investigators have not yet defined how the clock's ticking signals the approach of cellular oblivion.

In a study published in the Oct. 3, 2010, issue of Nature Structural and Molecular Biology, a team led by Jan Karlseder, Ph.D., at the Salk Institute for Biological Studies reports that as cells count down to senescence and telomeres wear down, their DNA undergoes massive changes in the way it is packaged. These changes likely trigger what we call "aging".

"Prior to this study we knew that telomeres get shorter and shorter as a cell divides and that when they reach a critical length, cells stop dividing or die," said Karlseder, an associate professor in the Molecular and Cell Biology Laboratory. "Something must translate the local signal at chromosome ends into a huge signal felt throughout the nucleus. But there was a big gap in between."

Karlseder and postdoctoral fellow Roddy O'Sullivan, Ph.D., began to close the gap by comparing levels of proteins called histones in young cells-cells that had divided 30 times-with "late middle-aged" cells, which had divided 75 times and were on the downward slide to senescence, which occurs at 85 divisions. Histone proteins bind linear DNA strands and compress them into nuclear complexes, collectively referred to as chromatin.

Karlseder and O'Sullivan found that aging cells simply made less histone protein than do young cells. "We were surprised to find that histone levels decreased as cells aged," said O'Sullivan, the study's first author. "These proteins are required th
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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

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