The intestinal colonization patterns of phm 2 mutant worms, which have a poorly functioning pharynx, indicate that large amounts of bacteria pass through

the grinder intact. These animals have life spans considerably shorter than wild-type worms, and concomitantly higher numbers of E. coli in the gut lumen [32]. Interestingly, bacteria are considered to play only a minor role in the decline of this organ, implying that degeneration Ro 61-8048 in vitro of the pharynx was due predominantly to the effects of long-term pumping [13]. Feeding C. elegans pathogenic bacteria such as Salmonella or Serratia marcescens degrades performance of the pharyngeal grinder and allows early passage of bacterial cells to the worm intestine [34, 35]. Our results suggest that the type of E. coli diet can profoundly alter the “functional aging” of the pharynx. We speculate that the Q-less E. coli membranes may be especially fragile when subjected to the worm pharyngeal grinder due to the absence of Q, which normally serves to maintain membrane stability by acting as a crucial membrane chain-terminating antioxidant [36]. Taken together, these findings MM-102 order underscore the importance of efficient bacterial degradation, as the number of intact bacteria that make it past the pharyngeal grinder clearly impact worm survival. Replicating bacteria in the gut have already been implicated as a main contributor of

worm death [14]. Worms fed either UV-irradiated or antibiotic-treated OP50 Protein kinase N1 had increased survival [14, 18, 37]. Similarly, C. elegans exposed to UV-irradiated Enterica faecalis or Salmonella displayed greater survival than animals fed CH5424802 ic50 viable cells of these pathogenic strains [38, 39]. However, worms fed UV-irradiated GD1 E. coli exhibited shorter life span than worms fed untreated GD1 [18]. We have observed enhanced susceptibility of GD1 E. coli to UV treatment. We speculate that the UV-treatment of GD1 as performed previously [18] actually represents a vast overdose of that required for cell killing, and may result in a toxic food that fails to support larval development (data not shown). Alternatively, it

is possible that worms recognize metabolites produced by GD1 cells, similarly to those produced by OP50, and respond through up-regulation of antimicrobial genes. Thus, GD1 cells that are able to reside within the gut lumen may act to elicit different worm signaling pathways that control innate immunity and the expression of antimicrobial genes such as lys 8[40]. In our study, the delay in E. coli accumulation of the gut in worms fed GD1 confers a survival advantage in the animal, and it will be important to determine whether the GD1 diet-mediated longevity effects can be attributed to enhanced intestinal immunity through known signaling pathways [32]. The diminished proliferative capacity of the Q-deficient E.