Aging does not Enhance Experimental Cigarette Smoke-Induced COPD in the Mouse

Abstract

It has been proposed that the development of COPD is driven by premature aging/premature senescence of lung parenchyma cells. There are data suggesting that old mice develop a greater inflammatory and lower anti-oxidant response after cigarette smoke compared to young mice, but whether these differences actually translate into greater levels of disease is unknown. We exposed C57Bl/6 female mice to daily cigarette smoke for 6 months starting at age 3 months (Ayoung@) or age 12 months (Aold@), with air-exposed controls. There were no differences in measures of airspace size between the two control groups and cigarette smoke induced exactly the same amount of emphysema in young and old. The severity of smoke-induced small airway remodeling using various measures was identical in both groups. Smoke increased numbers of tissue macrophages and neutrophils and levels of 8-hydroxyguanosine, a marker of oxidant damage, but there were no differences between young and old. Gene expression studies using laser capture microdissected airways and parenchyma overall showed a trend to lower levels in older animals and a somewhat lesser response to cigarette smoke in both airways and parenchyma but the differences were usually not marked. Telomere length was greatest in young control mice and was decreased by both smoking and age. The senescence marker p21Waf1 was equally upregulated by smoke in young and old, but p16INK4a, another senescence marker, was not upregulated at all. We conclude, in this model, animal age does not affect the development of emphysema and small airway remodeling.

Soluble extracellular Klotho decreases sensitivity to cigarette smoke induced cell death in human lung epithelial cells

“…Ito et al , therefore, first proposed that COPD was a disease due to accelerated aging of the lung 45 , and others have supported this hypothesis 15, 46, 47 . Although age does not affect the development of emphysema and small airway remodeling 48 , Cosio et al later refined the aging hypothesis and proposed that COPD is a disease of young susceptible smokers that progresses over time, accelerating lung damage, and then manifesting itself later in life 47 . Consequently, the molecular mechanism of accelerated aging can provide several therapeutic targets for novel intervention strategies against COPD 16, 49 .…”

Effects of sex and chronic cigarette smoke exposure on the mouse cecal microbiome

“…Two mice died in the smoke-exposed ovariectomized group from acute bronchospasm. All smoke exposures were conducted using our standard nose-only smoke exposure system [23][24][25][26].…”

Experimental animal models for COPD: a methodological review

“…Increased total inflammatory cell counts were reported in BAL of animal models of COPD which were mostly due to an increase in macrophages and neutrophils counts [33, 64]. …”