Today, we will be looking at new research that may provide a new treatment option for those suffering from chronic obstructive pulmonary disease.
What is chronic obstructive pulmonary disease?
Chronic obstructive pulmonary disease, or COPD, is a progressive respiratory disease characterized by shortness of breath and cough with sputum production. It generally takes a long time to develop, so it is more common in people who are at least forty years old.
Many factors may contribute to this disease, including air pollution and genetics, although the main one is tobacco smoking, thereby making COPD a modern lifestyle disease and one that is expected to be the third leading cause of death worldwide in two years’ time.
With the passing of time, COPD becomes more and more debilitating until even everyday activities, such as getting dressed or walking, become difficult. The disease is often accompanied by other conditions with which it shares some risk factors, including high blood pressure, diabetes, and osteoporosis.
Even though COPD is heavily influenced by external factors, it can be seen as a disease of accelerated lung aging, given that it is also characterized by chronic inflammation. Evidence pointing in this direction has been known for a while , and recently, researchers from Osaka University have proposed a new mouse model for both COPD and accelerated aging .
The new model
In their study, the researchers created mice with gene knockouts (disabling) of CD9, CD81, and both CD9 and CD81, halting the production of either, or both, of the homonymous proteins. These proteins are part of a family known as tetraspanins, cell-surface proteins located on the cellular membranes of the tissues of multiple organs. In particular, the CD9 and CD81 tetraspanins are abundantly expressed in the lung.
Both varieties of single-knockout mice exhibited similar health conditions because of the specific proteins they lacked, but the double-knockout ones had it much worse, as they developed not only a COPD-like condition but also some of the other diseases that often accompany COPD in human patients, including osteoporosis, emphysema, atrophy of the skin, and cataracts, leading the researchers to think that knocking out both genes contributes to the development of an accelerated aging syndrome.
Results of the study
While at three weeks of age, the double knockouts were indistinguishable from the controls, at eighty weeks, they were smaller and had more aged-looking hair. They lost body weight, bone mineral density, and adipose tissue; experienced thymic involution, and had a much shorter lifespan than the controls. Single-knockout mice did not appear to exhibit as many features typical of aging, and neither did younger double-knockout mice. At the age of one month, double-knockout mice didn’t seem to show any change in physical activity or signs of immunosenescence, though they did at six and eighteen months.
The disabling of both CD9 and CD81 also appeared to increase apoptosis and inflammation while decreasing cell proliferation, which are typical symptoms of COPD and aging.
Why does this happen?
According to the findings, the deletion of both CD9 and CD81 seems to downregulate the expression of SIRT1—a gene with an important role in cellular stress management—which also happens in chronic inflammatory conditions as well as aging. As single-knockout mice did not exhibit so many signs of accelerated aging, it appears that both genes play a role in maintaining the expression of SIRT1, preventing senescence and inflammaging.
The researchers suggested that pharmacological modulation of CD9, CD81, and tetraspanins, in general, may, therefore, be a novel therapeutic strategy for both COPD and aging. It’s good to know that we might have a new weapon against age-related diseases and that more and more researchers are not afraid to talk about aging as a target for medical intervention.
 Ito, K., & Barnes, P. J. (2009). COPD as a disease of accelerated lung aging. Chest, 135(1), 173-180.
 Jin, Y., Takeda, Y., Kondo, Y., Tripathi, L. P., Kang, S., Takeshita, H., … & Morimura, O. (2018). Double deletion of tetraspanins CD9 and CD81 in mice leads to a syndrome resembling accelerated aging. Scientific reports, 8(1), 5145.