A University of Rochester scientist discovered that the toxins in cigarette smoke wipe out a gene that plays a vital role in protecting the body from the effects of premature aging.
Without this gene we not only lose a bit of youthfulness – but the lungs are left open to destructive inflammation and diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer.
By identifying the Sirtuin ( SIRT1) gene's role in pulmonary disease, scientists also hope to find ways to restore it and jump-start lung healing. They've begun testing the powerful antioxidant resveratrol, which is extracted from red grape skins, to develop a treatment to target SIRT1 and reverse lung damage, or at least enhance the way standard COPD therapies work.
“This novel protein will allow us to program our body's immune-inflammatory system against lung damage and premature aging. The hallmark of this discovery is that we may be able to provide remedies to millions of smokers who would like to quit but cannot kick their addiction, and millions of former smokers who, despite quitting, remain at risk for illness as they age,” said Irfan Rahman, Ph.D., associate professor of Environmental Medicine and an investigator in the University of Rochester's Lung Biology and Disease Program.
The research was published in two separate studies, in the American Journal of Respiratory Critical Care Medicine,appearing online Jan. 3, 2008, and in the American Journal of Physiology, appearing Dec. 27, 2007 .
Approximately 23 million Americans have COPD, which is induced by inflammation and results in progressive breathlessness. By the year 2020, it is expected to be the third leading cause of death worldwide; today at least 9 percent of the elderly population is estimated to suffer from debilitating lung conditions.
Rahman has spent years studying how the 4,700 toxic chemical compounds in cigarettes assault lung tissue. He also focuses on why some people seem genetically predisposed to develop lung diseases while others are more fortunate, despite being smokers.
SIRT1 plays a pivotal role in the puzzle. It belongs to a class of genes that regulate chronic inflammation, cancer and aging. When SIRT1 is highly active, or over-expressed in mice, worms and fruit flies, their life spans are greatly increased. Recent studies also show that SIRT1 plays a positive role in stress resistance, metabolism, apoptosis and other processes involved in premature aging. However, environmental stress such as cigarette smoke or pollution can decrease production of SIRT1 in the lungs.
In collaboration with Vuokko L. Kinnula, M.D., at Helsinki University Hospital in Finland, Rahman's team studied the levels of SIRT1 in the lungs of nonsmokers and smokers with and without COPD. Thirty-seven patients from Helsinki who were undergoing either a lung resection for suspected cancer or a lung transplant, volunteered to provide tissue samples for the study. Researchers confirmed that SIRT1 was significantly lower in smokers who had COPD and in smokers who did not have disease, compared to nonsmokers.