Protective role of caffeine in carbon nanoparticle-induced lung and vascular aging - focus on mitochondrial functionality

Coffee consumption has been inversely correlated with total as well as cause-specific mortality, such as heart disease and diabetes, whereas a positive correlation was found with cancer-related deaths. In addition, several studies have shown that consumption of caffeinated beverages is associated with lower risk for coronary heart disease mortality, specifically in older subjects. We have unraveled a molecular mechanism explaining the protective effects of caffeine. Our data define an increase in mitochondrial p27, which causes improvement of mitochondria-dependent processes, as a new mode of action of caffeine. Moreover, we demonstrated that carbon nanoparticles induce cellular senescence, reduce mitochondrial Telomerase Reverse Transcriptase and increase oxidative stress. Therefore, we hypothesize that carbon nanoparticles, in integral component of air pollution, induce mitochondrial dysfunction, which is one reason for the increased senescence seen in lung and vessel, that could possibly be counteracted by caffeine.

Thus, we will perform comprehensive analyses of mitochondrial functions in mitochondria isolated from cells treated with carbon nanoparticles. We will then treat those cells with caffeine to ameliorate the expected mitochondrial dysfunction induced by carbon nanoparticles. We will also investigate the impact of pre- and post-incubation with caffeine in those cells to elucidate whether caffeine is not only preventive, but also therapeutically effective. In vivo, we will determine whether caffeine in drinking water can protect from carbon nanoparticle-induced dysfunctionality of the lung and the aorta of exposed mice.