The incidence of acute lung injury and pulmonary fibrosis is highest in older people, independent of other risk factors. Aging is associated with an increase in oxidative stress, a shift toward a type 2 immune response, and senescence of bone marrow-derived stem cells, all changes that could be associated with increased susceptibility of the lungs to injury and dysrepair (fibrosis). Previously, we demonstrated (1) in humans with ARDS that clinical prognosis correlates with the number of circulating endothelial progenitor cells; (2) in mice, bone marrow suppression increases lung injury after intratracheal instillation of bleomycin; and (3) infusion of mesenchymal stem cells reduces the severity of bleomycin-induced lung injury. To determine whether aging would increase susceptibility of the lungs to injury and dysrepair, we compared the response to intratracheal bleomycin in senescence-accelerated mice (SAMP), which age rapidly and have a reduced life span, with responses in normal age-matched control animals. Twelve-month-old (but not 6 month old) SAMP mice had an exaggerated inflammatory response (BAL levels of IL-6, KC, MCP-1, and G-CSF higher and IFNg lower than controls) 7 d after bleomycin. Bleomycin-induced fibrosis was more severe in both 6- and 12-month-old SAMP mice compared to age-matched controls. Serum glutathione redox potential was more oxidized in SAMP mice and appeared to increase from 6 to 12 months of age. We conclude that aging increases susceptibility of the lungs to inflammatory injury and fibrosis and that exaggerated fibrogenesis is more sensitive to senescence than is increased inflammation. We speculate that this is due to altered immune (Th2 bias) and reparative (stem cell) responses that result from cumulative oxidant stress associated with aging.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.