Sirtuin 1 and aging theory for chronic obstructive pulmonary disease

Abstract

Chronic Obstructive Pulmonary disease (COPD) is an inflammatory syndrome that represents an increasing health problem, especially in the elderly population. Drug therapies are symptomatic and inadequate to contrast disease progression and mortality. Thus, there is an urgent need to clarify the molecular mechanisms responsible for this condition in order to identify new biomarkers and therapeutic targets. Processes including oxidant/antioxidant, protease/antiprotease, and proliferative/antiproliferative balance and control of inflammatory response become dysfunctional during aging as well as in COPD. Recently it was suggested that Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to oxidative stress and chronic inflammation, is implicated in both development and progression of COPD. The present review focuses on the involvement of SIRT1 in the regulation of redox state, inflammation, and premature senescence, all crucial characteristics of COPD phenotypes. Recent evidence corroborating the statement of the "aging theory for COPD" was also discussed.

Figure 1

“The aging theory of COPD.” Several molecules involved in aging are also implicated in COPD pathogenesis: mutations in TERT are responsible for telomeres shortening; decreased Nrf2 can explain the excessive oxidative stress that causes damage and inflammation during both aging and COPD. Recent studies have suggested a crucial role of SIRT1 in COPD. Aging of lung is characterized by reduction in SIRT1 activity and expression. Decreased levels of SIRT1 lead to increased acetylation of NF-κB and are responsible for a persistent activation of proinflammatory molecules, such as IL8 and MMP9, and also for raised levels of senescence through accumulation of oxidants at cellular constituents (DNA, lipid, and protein). At the same time, COPD and smoking habit are associated with decreased SIRT1 activity and consequently increased inflammation and senescence. Finally, a vicious circle occurs with inflammation and senescence that further deteriorate COPD and aging conditions.