 | Normal human lung fibroblasts (shown on left) divide and maintain structural integrity. In contrast, lung fibroblasts exposed to cigarette smoke (shown on right) stop dividing and accumulate beta galactosidase (appears in blue), an enzyme that is a marker of an aging cell. |
February 7, 2009 — Smoking
doesn’t just make you look older—it actually accelerates aging. Toru Nyunoya,
M.D., of the University of Iowa revealed a connection between
Werner’s syndrome, a rare hereditary premature aging disease, and cell damage
that comes from smoking, both of which result in accelerated cell aging.
The
investigation found that a key protein which is defective in Werner’s syndrome,
resulting is the onset of accelerated cell senescence and aging is diminished in
smokers with emphysema. This decrease not only accelerates cell aging, it also
harms the cells that normally help repair damage in the lungs. The findings were
published in the second issue for February of the American Journal of Respiratory and
Critical Care Medicine.
"Smoking
can accelerate the aging process and shorten the lifespan by an average of more
than 10 years. We focused on what happens within the lungs because of the
similar aging effects, including atherosclerotic diseases and cancer, seen in
people with Werner’s syndrome and people who smoke," said Dr. Nyunoya, assistant
professor at the University of Iowa Carver College of Medicine and a
pulmonologist with University of Iowa Hospitals and Clinics.
To
determine the underlying mechanism, the investigators compared lung fibroblasts
taken from both nonsmokers without lung disease and patients with a heavy
smoking history and severe emphysema. "Werner’s
syndrome involves a genetic mutation that causes a deficiency in the protein
known as WRN. WRN normally helps repair DNA damage," Nyunoya said. The study
found that, while exposure to cigarette smoke did not cause the same genetic
mutation, the steady state levels of WRN was decreased by other means, leading
to the same effect. The affected cells had also lost their ability to divide or
grow, confirming that smoking habits cause cell aging.
The
team also applied cigarette smoke extract to cultured lung fibroblasts taken
from nonsmokers. After cigarette smoke exposure, WRN expression was decreased,
indicating a direct causal action. In contrast, when the team caused the lung
fibroblasts in Petri dishes to overexpress Werner’s syndrome protein, it had a
protective effect and helped resist the damaging effects of cigarette smoke.
The
researchers plan future studies using mouse models
to further analyze the effects of smoking on Werner’s syndrome protein.
"Overall, our study may support efforts to target Werner’s syndrome protein for
use in developing treatments for smoking-related conditions such as emphysema,"
Nyunoya said.
Full
text :
www.thoracic.org/sections/publications/press-releases/resources/021509-nyunoya.pdf
— News release courtesy of American Thoracic Society.