Researchers at Duke University Medical Center have discovered a mechanism that helps to explain the stress response in terms of DNA damage.

“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," said senior author Robert J. Lefkowitz, M.D., James B. Duke Professor of Medicine and Biochemistry and a Howard Hughes Medical Institute (HHMI) investigator at Duke University Medical Center. The paper was published in the online issue of Journal Nature.

In the study, mice were infused with an adrenaline-like compound that works through a receptor called the beta adrenergic receptor. The researchers found that this model of chronic stress triggered certain biological pathways that resulted in accumulation of DNA damage.

"This could give us a plausible explanation of how chronic stress may lead to a variety of human conditions and disorders, which range from merely cosmetic, like graying hair, to life-threatening disorders like malignancies," Lefkowitz said.

"The study showed that chronic stress leads to prolonged lowering of p53 levels," said Makoto Hara, Ph.D., a postdoctoral fellow in the Lefkowitz laboratory. P53 is a tumor suppressor protein preventing genome abnormalities.

"We hypothesize that this is the reason for the chromosomal irregularities we found in these chronically stressed mice," says Mr. Hara.

Researchers found that a molecular mechanism through which adrenaline like compounds trigger DNA damage.

The infusion of an adrenaline like compound for four weeks in the mice caused degradation of p53, which was present in lower levels over time.

The study showed that DNA damage was prevented in mice lacking the adrenaline-like compound beta arrestin 1, loss of beta arrestin 1 stabilized cellular levels of p53.