Chest
Volume 135, Issue 1, January 2009, Pages 173-180
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Translating Basic Research into Clinical Practice
COPD as a Disease of Accelerated Lung Aging

https://doi.org/10.1378/chest.08-1419Get rights and content

There is increasing evidence for a close relationship between aging and chronic inflammatory diseases. COPD is a chronic inflammatory disease of the lungs, which progresses very slowly and the majority of patients are therefore elderly. We here review the evidence that accelerating aging of lung in response to oxidative stress is involved in the pathogenesis and progression of COPD, particularly emphysema. Aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death. This results from a failure of organs to repair DNA damage by oxidative stress (nonprogrammed aging) and from telomere shortening as a result of repeated cell division (programmed aging). During aging, pulmonary function progressively deteriorates and pulmonary inflammation increases, accompanied by structural changes, which are described as senile emphysema. Environmental gases, such as cigarette smoke or other pollutants, may accelerate the aging of lung or worsen aging-related events in lung by defective resolution of inflammation, for example, by reducing antiaging molecules, such as histone deacetylases and sirtuins, and this consequently induces accelerated progression of COPD. Recent studies of the signal transduction mechanisms, such as protein acetylation pathways involved in aging, have identified novel antiaging molecules that may provide a new therapeutic approach to COPD.

Section snippets

Aging Process and Its Molecular Mechanism

Senescence or aging is defined as the progressive decline of homeostasis that occurs after the reproductive phase of life is complete, leading to an increasing risk of disease or death. Kirkwood3 has advanced the concept of “disposable soma,” in which aging, rather than being programmed and determined by selected genes, results from the stochastic interaction between injury and repair, as the result of the energy devoted by an individual to maintain organ integrity and protect DNA against

Aging and Lung Function/Structural Change

The classical epidemiologic studies of Fletcher and Peto19 demonstrated that death and disability from COPD were related to an accelerated decline in lung function with time, with a loss of 50 to 100 mL in FEV1 per year, but even in healthy volunteers there is a loss of 20 mL per year with aging (Fig 1). Janssens and coworkers20 demonstrated that physiologic aging of the lung is associated with dilatation of alveoli with an enlargement of airspaces and a decrease in gas exchange surface area,

Aging and Inflammation

Most age-associated diseases, such as Alzheimer disease, cataract, rheumatoid arthritis, osteoporosis, and cardiovascular disease as well as COPD, involve chronic inflammation, including infiltration of inflammatory cells and higher circulating or local concentrations of proinflammatory cytokines. Increased production of oxygen-derived free radicals is a primary driving force for aging and activate redox-sensitive transcriptional factors, such as activator protein-1 and nuclear factor-κB

Similarities Between Aged Lung and COPD Lung

It is not clear how the aging process is involved in the decline of lung function and inflammation in COPD. However, there are a lot of similarities between aged lung and COPD lung (Table 2). Especially, there have been important advances in understanding the molecular mechanisms of ages, and several of these pathways are relevant to accelerated lung aging in COPD patients.

As shown in the model in Figure 1, lung function is declined in COPD quicker than normal aged lung. The lung function/age

Therapeutic Implications

Greater understanding of the molecular mechanisms of aging has revealed several novel targets for drug development, and since these processes are involved in the pathogenesis of emphysema this may lead to new treatments for COPD. From the oxidative stress/aging theory and the fact that oxidative stress is major risk factor of COPD, antioxidants are likely to be effective antisenescence drugs or anti-COPD drugs. Currently available antioxidants, such as N-acetyl cysteine, are not very potent and

Conclusion and Future Directions

The link between aging and the pathogenesis of COPD is strongly supported by numerous studies.46, 47, 48, 49, 50 Senescence is a complex outcome of both intrinsic and environmental factors, especially oxidative stress, and therefore the role of cigarette smoke/noxious gas is a key factor linking aging lung to COPD. However, the molecular mechanisms are not yet been fully explored. Recently, a number of antiaging molecules have been identified, and evaluation of these molecules in patients with

Acknowledgment

We regret that owing to space constraints we were not able to cite all the important original publications and apologies to those authors whose work we have not cited.

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