Current reporter assay technologies enabled us to perform high throughput screening of chemical libraries. The isolation of candidate molecules is dependent on the choice of reporter protein and the construction of efficient cell-or animal-based assays. The identification of CR mimetics is attractive for the development of anti-aging therapeutics. While CR mimetics may not be a 'cure-all' for ageassociated disorders, they may suppress and/or delay the progression of various kinds of refractory diseases. Importantly, pharmaceutical companies do not have a high incentive to develop drugs for rare diseases. Therefore, academic laboratories are perfectly placed to develop drugs for rare disorders by using phenotypic cell-or animal-based reporter assay systems. Although candidate CR mimetics identified in such systems must still be validated to show that their beneficial effects are similar to those provided by CR, CR mimetics offer great potential to solve the unmet medical needs of rare diseases and common age-related disorders. We have focused on bioassay (protein reporter assay) screening systems in this review, but biosensor technologies (analytical devices consisting of biological components) are also important for drug discovery [36] . Therefore, the development of biosensors to screen CR mimetics will also be an important approach to future drug discovery efforts. Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC)) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B) adenosine receptor (A(2B)AR), largely abolished the adenosine-stimulated chloride transport, suggesting that A(2B)AR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2B)AR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections. Alcohol abuse is a risk factor for pulmonary infections. It is not fully understood how alcohol exposure compromises the lung host defense. Previous studies suggest that multiple pathophysiological mechanisms may be involved [1, 2, 3] . Airway mucosal immunity and mucociliary clearance are the two primary host defense mechanisms, which take place in a thin layer of liquid on the top of airway epithelia, known as airway surface liquid (ASL). ASL, composed of a gel-like mucus layer and a sol-like periciliary liquid layer [4, 5, 6] , is the ''battlefield'' for pulmonary infection and immunity. The viscous mucous blanket traps inhaled microorganisms and particles to restrict their spreading in the lung. In contrast, the watery periciliary liquid (PCL) underneath pools antimicrobial substances, antibodies, cytokines, chemokines and other immune modulators [7, 8, 9] . More importantly, PCL provides the milieu for innate and adaptive immune cells including neutrophils and macrophages to home and function. Moreover, PCL prevents cilia from being entrapped in viscous mucus and bathes them for mechanical movement for mucociliary clearance [5, 10] .