Cellular Senescence in Aging versus Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is caused by long-term inhalation of smoke or other particulate or chemical irritants. In wealthier parts of the world, that usually means smoking. In less wealthy parts of the world, cooking fires and industrial processes also contribute. The condition shares some mechanisms with aging, particularly the accumulation of senescent cells and the chronic inflammation produced by those cells. In some ways, it is possible to consider aspects of COPD to be accelerated lung aging. In other ways it is entirely different. This is generally true of the environmental contributions that make up secondary aging, the various exposures that cause harm and dysfunction by speeding up specific, narrow forms of cell and tissue damage. The open access paper here is interesting for the comparisons it draws between aging and smoking as causes of increased cellular senescence in the lungs.

Most parts of the body including the lungs experience progressive damage with aging as well as impaired function. Lung aging is associated with loss of elasticity, a decrease in pulmonary function, loss of structural integrity, and an increase in inflammation which are among the key characteristics of chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of chronic morbidity and mortality on a global scale. Growing evidence suggest that age-associated structural and functional alterations enhance pathogenetic susceptibility to COPD.

Along with other toxic gases, the most common etiological factor that develops COPD is cigarette smoke (CS) which results in several pathophysiological changes in the lung. Recent reports suggest that CS induces oxidative stress-mediated DNA damage and triggers cellular senescence in the lungs. Cellular senescence is a process of complete and permanent cell cycle arrest. The accumulation of metabolically active senescent cells in tissues during aging impairs tissue repair and function. Pro-inflammatory mediators are secreted which give rise to a phenomenon known as senescence-associated secretory phenotype (SASP). Senescent cells increase the damage of neighboring cells by virtue of their SASP phenotype. Previous reports proposed a network of cellular senescence, inflammatory response, and premature lung aging in the pathogenesis of COPD.

We hypothesized that aging-associated changes in lungs worsen the COPD by CS exposure. Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls. CS caused a decline in lung function and affected the lung structure of both groups of mice. No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation. Aging per se increased lung cellular senescence. Thus our data suggest that normal aging and chronic CS exposure independently induce cellular senescence in the lungs.

Link: https://doi.org/10.1038/s41598-018-27209-3


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