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

roughout the genome, and therefore any event that disrupts this production line affects the stability of the entire genome."

The team then undertook exhaustive "time-lapse" comparisons of histones in young versus aging cells and confirmed that marked differences in the abundance and variety of histones were evident at every step as cells moved through cell division.

O'Sullivan calls the "default" histone pattern displayed by young cells "happy, healthy chromatin." By contrast, he says, aging cells appear to undergo stress as they duplicate their chromosomes in preparation for cell division and have difficulty restoring a "healthy" chromatin pattern once division is complete.

Comparisons of histone patterns in cells taken from human subjects-a 9- versus a 92-year-old-dramatically mirrored histone trends seen in cell lines. "These key experiments suggest that what we observe in cultured cells in a laboratory setting actually occurs and is relevant to aging in a population," says Karlseder.

The initiation of diseases associated with aging, such as cancer, is largely attributed to DNA, or genetic, damage. But this study suggests that aging itself is infinitely complex: that progressive telomere shortening hastens chromosomal aging by changing the way genes entwine with histones, so-called "epigenetic" changes. How DNA interacts with histones has enormous impact on whether genes are expressed-hence the current intense interest in the relationship of the epigenomic landscape to disease states.

Rescue experiments in which the team cosmetically enhanced aging cells confirmed that signals emitted by eroding telomeres drove epigenetic changes. When aging cells were engineered to express telomerase, the enzyme that restores and extends stubby telomeres, those rejuvenated cells showed histone levels reminiscent of "happy, healthy chromatin," and a partial return to a youthful chromatin profile.

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Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert  

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