The effects of age and carbon black on airway resistance in mice

Abstract

Rationale Ambient particulate matter (PM) is associated with acute exacerbations of airflow obstruction. Additionally, elderly individuals are more susceptible to increased functional morbidity following acute PM exposure. Hypothesis/Objective The purpose of the current study is to determine the aging effects of PM exposure on the responsiveness of airway smooth muscle in mice. We hypothesized that airway reactivity induced by methacholine (Mch) will increase with age in PM exposed mice. Methods Male C57BL/6 (B6) mice at 11, 39, 67, and 96 wks of age were exposed to either carbon black (CB concentration ~550 µg/m3) or room air (RA) for 3 hours on 3 consecutive days. One day after the last exposure, mice were anesthetized and airways resistance (Raw) was measured using forced oscillation at baseline and 1 minute after increasing half-log doses (0.1 to 30 mg/ml) of aerosolized Mch. Results Baseline Raw was significantly lesser in mice at 39, 67, and 96 wks compared with 11-wk old mice (p < 0.05). In RA exposed mice, an age-dependent decline in Mch-induced airway reactivity occurred in association with the highest Mch doses at ages 67 and 96 wks (p < 0.05). CB exposure caused a significant (p < 0.05) increase in Mch-induced Raw response in 67-wk old CB exposed mice compared with age-matched RA mice. Conclusion Our results show a progressive decrease in the Mch-induced Raw response with age in B6 mice. Overall, the effect of CB exposure resulted in significant increases in airway reactivity in middle-aged mice.

Enhanced allergic airway disease in old mice is associated with a Th17 response

“…Although young and old HDM mice had similar relative increases in AHR after methacholine challenge, young HDM mice showed greater sensitivity to methacholine compared to the old mice in the same treatment group, which is consistent with previous published findings [8,19]. Although young and old HDM mice had similar relative increases in AHR after methacholine challenge, young HDM mice showed greater sensitivity to methacholine compared to the old mice in the same treatment group, which is consistent with previous published findings [8,19].…”

“…3a). In general, old mice were less responsive to methacholine compared to young mice as suggested previously [8,19]. However, both, young and old mice developed increased AHR after HDM-treatment, and the relative response after HDM treatment was similar in both age groups.…”

The Influence ofNrf2on Cardiac Responses to Environmental Stressors

“…Targeted deletion of Nrf2 exacerbated the HR responses, though the mechanism through which Nrf2 protects against the response remains unclear. It would also be of interest to determine whether interactions exist between Nrf2 and preexisting disease and/or age, both of which are important susceptibility factors associated with PM exposure [50–54]. …”

Environmental Determinants of Lung Aging

“…89 Changes in muscarinic receptor subtypes and receptor coupling to G proteins are described with senescence, 90 which might account for the increase in bronchial responsiveness to methacholine challenge in the elderly 91 and to increased airway responsiveness to inhaled carbon black in older mice. 92 Response to β agonists is also impaired in older subjects. 93 Cysteinylleukotriene (CysLT1) receptors, but not corticosteroid receptors, undergo functional changes with age.…”

“…The effects of age and carbon black exposure on airway resistance in mice was studied by Bennett et al 92 Mice at 11, 39, 67, and 96 weeks were exposed to carbon black for 3 hours on 3 consecutive days. Baseline airway resistance was significantly lower in the oldest group of mice compared to the younger mice.…”