Cigarettes leave deadly path by purging protective genes

Jan 23, 2008

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.

The next step was to investigate what pathways lead to the depletion of SIRT1. Researchers found that Sirtuin also plays a role in regulating the entire chemical signaling system that protects the lungs from smoke and pollution. They investigated how SIRT1 relates to another key protective molecule, Nrf2, a transcription factor. Just as in the case of SIRT1, an airway deficient in Nrf2 is weak and inflamed and more prone to conditions such as COPD, researchers found.

Nrf2 was also important because it directly regulates several antioxidant genes such as gluthathione (GSH), the most abundant cellular antioxidant responsible for detoxifying the airways. Therefore, the pathway from SIRT1 to Nrf2 ultimately leads to the depletion of GSH, exacerbating the organ’s aging process.

“You can be 45 years old and look great on the outside, but if you are a smoker or former smoker, your lungs can easily be 60 years old because of the chemical assault,” Rahman said.

Other University of Rochester research teams are investigating the Nrf2 pathway and various ways to boost fundamental genetic changes in the body that would arm it with amplified natural antioxidants. The result could be the development of a target for new drugs that would protect us from age-related diseases such as cancer and emphysema.

Although he was not involved in the study, James D. Crapo, M.D., a leading expert in the field of lung disease and a professor of Medicine at the National Jewish Medical and Research Center, University of Colorado Health Sciences Center in Denver, said Rahman’s novel finding opens new doors. “This is certainly an important breakthrough in understanding the persistent lung damage and inflammation that occur in patients with COPD, and therapies can now be directed towards this protein.”

Source: University of Rochester Medical Center

Explore further: Muscular dystrophy: Repair the muscles, not the genetic defect

add to favorites email to friend print save as pdf

Related Stories

Researchers exploring collagen growth

3 minutes ago

Research by a biomedical engineer at Texas A&M University is shedding light on how collagen grows at the molecular level and helps form a diverse set of structures in the body, ranging from bone, tendon, ...

Underwater James Bond

23 minutes ago

NEEMO – NASA Extreme Environment Mission Operations – trains astronauts for life in space. Living and working in an underwater base is similar to being on a space station. This year, NASA has two NEEMO ...

Cutting electric vehicle energy use 51 percent

23 minutes ago

(Phys.org) —Researchers at the University of California, Riverside's Bourns College of Engineering have shown that a vehicle navigation tool they created can cut electric vehicle energy use up to 51 percent.

A map of comet 67P/Churyumov-Gerasimenko

23 minutes ago

High-resolution images of comet 67P/Churyumov-Gerasimenko reveal a unique, multifaceted world. ESA's Rosetta spacecraft arrived at its destination about a month ago and is currently accompanying the comet ...

A tabletop motor using an entirely new driving principle

33 minutes ago

A tabletop motor using an entirely new driving principle is under development at the headquarters of C-Motive Technologies, a startup business that is commercializing technology from the College of Engineering ...

Recommended for you

Dendritic cells affect onset and progress of psoriasis

Sep 12, 2014

Different types of dendritic cells in human skin have assorted functions in the early and more advanced stages of psoriasis report researchers in the journal EMBO Molecular Medicine. The scientists suggest that new strate ...

Approach to deadly sepsis infections continues to vary

Sep 12, 2014

Treatment practices for patients hospitalised with the potentially fatal infection known as "sepsis" will continue to vary because of individual differences between hospitals and countries, according to University of Adelaide ...

User comments : 0