Stress Cascade Explains DNA Damage

Stress and the fight-or-flight response it triggers, can lead to premature aging, tumors and neuropsychiatric conditions as well as damage to DNA. Now researchers have discovered one of what are likely multiple mechanism that cause this.

First they gave mice an adrenaline-like compound. This in turns triggered a beta adrenergic receptor, which triggered a biological pathways that lowered production of a tumor suppressor protein called P53. And P53 is known to prevent genomic abnormalities.

Being constantly flooded with adrenaline lowered p53 levels, they write, thus allowing genetic abnormalities to accumulate.

At the same time that the higher adrenaline levels were keeping the body from protecting itself from genetic abnormalities, they were also triggering DNA damage through another pathway. So stress functions as a one-two punch on DNA, leading to a buildup of all the unpleasant manifestations of chronic stress that so many in modern society are prey to. Mice and human cell lines have similar responses, so the researchers posit the cascade of negative effects may be similar in humans.

The paper is published in this week's online issue of the journal Nature.

"We believe this paper is the first to propose a specific mechanism through which a hallmark of chronic stress, elevated adrenaline, could eventually cause DNA damage that is detectable," author Robert Lefkowitz, a professor of medicine and biochemistry at Duke University Medical Center, said in a release.

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