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A multi-disciplinary team of researchers at UC San Diego announced Thursday that maintaining a cell’s ability to turn on and off a natural protective process for DNA could be a key to slowing down human aging.

Their study, published in the Proceedings of the National Academy of Sciences, focused on chromatin silencing, a natural biochemical process that converts specific regions of DNA from a loose, open state into a closed one, thus shielding DNA regions.

However, during the closed state, DNA regions are prevented from expressing RNAs and proteins that carry out biological functions, the scientists said. As a result, excessive silencing could derail normal cell physiology.

Doing experiments in yeast, the scientists found that a complete loss of chromatin silencing leads to accelerated cell aging and death, but that continuous silencing also leads cells to a shortened lifespan.

The experiments by the UCSD scientists solved the dilemma.

“Instead of staying in the silencing or silencing loss state, cells switch their DNA between the open, silencing loss, and closed, silencing, states periodically during aging,” said biologist Nan Hao, who led the research team. “In this way, cells can avoid a prolonged duration in either state, which is detrimental, and maintain a time-based balance important for their function and longevity.”

He said analyzing such dynamics in humans is likely to be much more complex and require more intricate studies.

“When cells grow old, they lose their ability to maintain this periodic switching, resulting in aged phenotypes and eventually death,” Hao said.

“The implication here is that if we can somehow help cells to reinforce switching, especially as they age, we can slow their aging,” he said. “And this possibility is what we are currently pursuing.”

He said further research could lead to new strategies to promote human longevity.

Faculty, students and postdoctoral fellows molecular biology, quantitative biology, bioengineering and biocircuits took part in the study, which was funded by, among others, the National Science Foundation, University of California Cancer Research Coordinating Committee and the Department of Defense.

—City News Service

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