Resveratrol decreases tobacco-induced inflammation in the lungs of smokers, suggesting that SIRT1 is involved in regulating the inflammatory response to cigarette smoke. Further evidence for a role for sirtuins in this process comes from Rajendrasozhan et al., in a study that confirms and extends the results of previous work.
The authors show once again that SIRT1 levels are low in the lungs of smokers, and that these levels diminish further in response to cigarette smoke. Smoke-exposed lung cells and macrophages exhibited increased inflammatory signaling (assayed primarily by looking at IL-8), as do cells in which SIRT1 has been artificially knocked out. Consistent with this, the RelA subunit of the master inflammation regulator NF-κB is hyperacetylated — recall that SIRT1 is a deacetylase — and consequently more active. Conversely, overexpression of SIRT1 decreases inflammatory cytokine production, echoing earlier results that described SIRT1 activation by resveratrol treatment.
Thus, a key longevity-assurance gene is also involved in restricting inflammation, which is a risk factor for some of smoking’s worst complications — chronic obstructive pulmonary disease (COPD) — as well as tumorigenesis. Tobacco is a major public health issue, so it’s not surprising that SIRT1 is getting attention in this context, but there is reason to believe that the phenomenon is general to organs other than the lung — e.g., see this review from Salminen et al., which describes how signaling from SIRT1 and FoxO transcription factors (mammalian homologs of the worm longevity gene DAF-16) can inhibit NF-κB signaling in a variety of systems. The authors close the circle by discussing the connection between longevity assurance and the mitigation of one specific age-related phenotype, inflammaging.
COPD is a leading cause of death worldwide, and it arises not only in smokers but in members of their households, as well as people exposed to environmental pollutants. A host of other inflammatory diseases, such as arthritis, beset the elderly and decrease quality of life. Increasing evidence that SIRT1 activity could mitigate the health harms of runaway inflammation point to even more potential uses for the new class of sirtuin-activating drugs that are currently under consideration as therapies against diabetes and metabolic syndrome.