“This study has found a common pathway whereby cigarette smoke impacts both pulmonary and neurophysiological function. Further, the results suggest the possible therapeutic value of targeting this pathway with compounds that could improve both lung and brain functions in smokers,” said Irfan Rahman, Ph.D., a researcher from the Department of Environmental Medicine at the University of Rochester Medical Center in Rochester, N.Y.
“We envisage that our findings will be the basis for future developments in the treatment of those patients who are suffering with tobacco smoke-mediated injuries and diseases.”
Rahman and colleagues found that tobacco smoke affects clock gene expression rhythms in the lung by producing parallel inflammation and depressed levels of brain locomotor activity.
Short- and long- term smoking decreased a molecule known as SIRTUIN1 (SIRT1, an anti-aging molecule) and this reduction altered the level of the clock protein (BMAL1) in both lung and brain tissues in mice, according to the researchers.
A similar reduction was seen in lung tissue from human smokers and patients with chronic obstructive pulmonary disease (COPD).
The researchers made this discovery using two groups of mice they placed in smoking chambers for short-term and long-term tobacco inhalation. One of the groups was exposed to clean air only and the other was exposed to different numbers of cigarettes during the day.
Researchers monitored their daily activity patterns and found that these mice were considerably less active following smoke exposure.
Scientists then used mice deficient in SIRT1 and found that tobacco smoke caused a dramatic decline in activity; this effect was weakened in mice that over- expressed this protein or were treated with a small pharmacological activator of the anti-aging protein.
Further results suggest that the clock protein, BMAL1, was regulated by SIRT1, and the decrease in SIRT1 damaged BMAL1, resulting in a disturbance in the sleep cycle/molecular clock in mice and human smokers. However, this defect was restored by a small molecule activator of SIRT1, the researchers noted.
The study was published in The Federation of American Societies for Experimental Biology Journal.