© 2007 American Thoracic Society
Aging, the Aging Lung, and Senile Emphysema Are DifferentFrom the Author:My editorial's intent was to highlight the cellular and molecular events that mechanistically link aging and chronic obstructive pulmonary disease (COPD), and to stimulate further research on this important topic (1). Such studies may help resolve the controversies raised by Drs. Teramoto and Ishii regarding the definition of aging, whether aging should be interpreted as a physiologic or pathologic process, and the relationship between lung alterations due to aging vis-à-vis senile emphysema. It is apparent that the concept of a so-called physiologic lung aging, as argued by Drs. Teramoto and Ishii, deserves careful revaluation. Significant pathologic processes are evident with the onset of aging, such as excessive oxidative stress, DNA damage, enhanced inflammation, and decreased immunity, all of which might contribute to a significantly higher incidence of cancer and degenerative diseases compromising the heart (with heart failure), muscle (with muscle wasting), and joints (with osteoporosis), among others (2). Why should the lung be different from the heart, brain, or immune system? It is conceivable that age-related molecular and cellular injuries may be of significant pathophysiologic importance in the causation of many pulmonary diseases, including COPD or lung cancer. Indeed, prior work by Dr. Teramoto acknowledges the close resemblance of lung alterations due to aging to those related to environmental injuries (including cigarette smoke inhalation). He raises similar considerations regarding the effect of age on cigarette smoke–induced emphysema to those posed in my editorial and the accompanying article by Sato and coworkers (3). Aging alters fundamental controls involved in cell growth, maintenance, and death. Accumulation of stresses over the life span shortens telomeres, a hallmark of senescent cells (4). Telomere shortening was recently recognized to be present in COPD lungs in association with increased expression of Ink4a/Arf (5), a biomarker of aging (6). These advances and the recognition of alveolar cell apoptosis, oxidative stress, and senescence have been linked to emphysematous lung destruction (5, 7), warranting the revaluation of prior definitions of alveolar enlargement in both diseased (i.e., COPD) and aging lung (8). Transgenic mice provide important and useful tools for exploring how candidate genes, such as SMP-30 and the Klotho protein, trigger pathogenetic mechanisms involved in destructive alveolar enlargement. These studies will enrich the list of candidate genes potentially involved in aging and in COPD in humans. In addition, these discoveries will further clarify how COPD risk factors, including sex, childhood diseases, cigarette pack-years, and infections might also enhance the susceptibility to the disease.
Johns Hopkins University School of Medicine, Baltimore, Maryland FOOTNOTES Conflict of Interest Statement: R.M.T. has received $2,500 for a lecture given in a meeting on COPD sponsored and organized by AstraZeneca. He has received an unrestricted gift of $100,000 from Quark Biotech to conduct research in the pathogenesis of emphysema, particularly of the pathway involving RTP-801. REFERENCES
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