SIRT 1 and oxidative stress in COPD pathogenesis

Background: Increasing evidence indicates that oxidative stress and inflammation are strictly correlated to cellular senescence and aging. SIRT1, an anti-aging, anti-oxidative and anti-inflammatory protein, represents a connecting link among these processes characterizing COPD. Objectives: 1) to compare the expression and activity of SIRT 1 in the peripheral blood mononuclear cells (PBMC) of smokers, non smokers and COPD patients; 2) to investigate the association between SIRT1 and markers of oxidative stress and inflammation and 3) to assess the correlation between the markers of oxidative stress, SIRT1 and lung function. Methods: total oxidative status (TOS), total antioxidant capacity (TAC) and Oxidative Stress Index (OSI) in plasma, SIRT1 expression and activity levels, and IL-6 levels in PBMCs were measured in nonsmokers (NS), smokers (S) and COPD. Results: OSI was higher in COPD than in controls both for S (p = 0.04) and NS (p <0.0001). TOS was similar between COPD and S, but was higher in COPD when compared to NS (p <0.0001). TAC was lower in COPD compared to S (p = 0.03) and NS (p = 0.007), while there were no differences between S and NS. IL-6 levels were higher in COPD than in controls, but the differences were not statistically significant. The expression of SIRT1 was similar in the two control groups and was lower in COPD compared to NS (p 0.04), of note SIRT1 activity was decreased in COPD compared to S (p 0.001) and NS (p 0.001). SIRT1 activity was inversely correlated to respiratory function in COPD patients but not in control subjects. Conclusion: SIRT1 and oxidative stress seem to be actively involved in COPD pathogenesis.SIRT1 could be a promising therapeutic target for COPD in the future.