Dataset Information

Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung.

ABSTRACT:

Rationale

Cigarette smoke (CS) is the leading cause of chronic obstructive pulmonary disease, accounting for more than 90% of cases. The prevalence of chronic obstructive pulmonary disease is much higher in the elderly, suggesting an age dependency. A prominent defense against the oxidant burden caused by CS is the glutathione (GSH) adaptive response in the lung epithelial lining fluid (ELF) and tissue. However, as one ages the ability to maintain GSH levels declines.

Objectives

Examine the effect of aging on the GSH adaptive response to CS and resulting lung sensitization to inflammation and oxidation.

Methods

Both young (2 mo old) and aged (8, 13, 19, and 26 mo old) mice were used to study the effects of age on the GSH adaptive response after an acute exposure to CS.

Measurements and main results

Young mice had a robust sixfold increase in ELF GSH after a single exposure to CS. The GSH response to CS decreased as a function of age and diminishes in the older mice to only a twofold increase over air controls. As a consequence, levels of CS-induced tumor necrosis factor-? and nitric oxide synthase, markers of inflammation, and 8-hydroxy-2-deoxyguanosine, a marker of DNA oxidation, were elevated in the aged mice compared with the young mice. Additionally, depletion of ELF GSH with buthionine sulfoximine in young mice recapitulated changes in ELF tumor necrosis factor-? as seen in old mice.

Conclusions

These data suggest that the age-related maladaptive response to CS sensitizes the lung to both inflammation and oxidation potentially contributing to the development of CS-induced chronic obstructive pulmonary disease.

SUBMITTER: Gould NS

PROVIDER: S-EPMC3001254 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung.

Gould Neal S NS Min Elysia E Gauthier Steven S Chu Hong Wei HW Martin Richard R Day Brian J BJ

American journal of respiratory and critical care medicine 20100709 9

<h4>Rationale</h4>Cigarette smoke (CS) is the leading cause of chronic obstructive pulmonary disease, accounting for more than 90% of cases. The prevalence of chronic obstructive pulmonary disease is much higher in the elderly, suggesting an age dependency. A prominent defense against the oxidant burden caused by CS is the glutathione (GSH) adaptive response in the lung epithelial lining fluid (ELF) and tissue. However, as one ages the ability to maintain GSH levels declines.<h4>Objectives</h4>E ...[more]

PMID: 20622027

Similar Datasets

Project description:BACKGROUND:Lung aging is characterized by a number of structural alterations including fibrosis, chronic inflammation and the alteration of inflammatory cell composition. Chronic exposure to cigarette smoke (CS) is known to induce similar alterations and may contribute to premature lung aging. Additionally, aging and CS exposure are associated with transcriptional alterations in the lung. The current work aims to explore the interaction between age- and CS- associated transcriptomic perturbations and develop a transcriptomic clock able to predict the biological age and the impact of external factors on lung aging. RESULTS:Our investigations revealed a substantial overlap between transcriptomic response to CS exposure and age-related transcriptomic alterations in the murine lung. Of particular interest is the strong upregulation of immunoglobulin genes with increased age and in response to CS exposure, indicating an important implication of B-cells in lung inflammation associated with aging and smoking. Furthermore, we used a machine learning approach based on Lasso regression to build a transcriptomic age model that can accurately predict chronological age in untreated mice and the deviations associated with certain exposures. Interestingly, CS-exposed-mice were predicted to be prematurely aged in contrast to mice exposed to fresh air or to heated tobacco products (HTPs). The accelerated aging rate associated with CS was reversed upon smoking cessation or switching to HTPs. Additionally, our model was able to predict premature aging associated with thoracic irradiation from an independent public dataset. CONCLUSIONS:Aging and CS exposure share common transcriptional alteration patterns in the murine lung. The massive upregulation of B-cell restricted genes during these processes shed light on the contribution of cell composition and particularly immune cells to the measured transcriptomic signal. Through machine learning approach, we show that gene expression changes can be used to accurately monitor the biological age and the modulations associated with certain exposures. Our findings also suggest that the premature lung aging is reversible upon the reduction of harmful exposures.

Dataset Information

Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung.

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung.

Similar Datasets

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