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 p21(Waf1) was equally upregulated by
smoke in young and old, but
p16(INK4a), 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.