Aging does not enhance experimental cigarette smoke-induced COPD in the mouse.
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.
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
Steven
S
Zhou
Joanne L
JL
Wright
Joseph
J
Liu
Don D
DD
Sin
Andrew
A
Churg
D000375:Aging / Q000473:pathology*; D056151:Airway Remodeling; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016922:Cellular Senescence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D016615:Telomere / Q000235:genetics
D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger; D006151:Guanosine; C046215:8-hydroxyguanosine