pmk-1

The type of food source has previously been shown to be as important as the level of food intake in influencing lifespan. Here we report that different Escherichia coli food sources alter Caenorhabditis elegans lifespan. These effects are modulated by different subsets of sensory neurons, which act with nmur-1, a homolog of mammalian neuromedin U receptors. Wild-type nmur-1, which is expressed in the somatic gonad, sensory neurons, and interneurons, shortens lifespan only on specific E. coli food sources-an effect that is dependent on the type of E. coli lipopolysaccharide structure. Moreover, the food type-dependent effect of nmur-1 on lifespan is different from that of food-level restriction. Together our data suggest that nmur-1 processes information from specific food cues to influence lifespan and other aspects of physiology.

Diet profoundly affects metabolism and incidences of age-related diseases. Animals adapt their physiology to different food-types, modulating complex life-history traits like aging. The molecular mechanisms linking adaptive capacity to diet with aging are less known. We identify FLR-4 kinase as a novel modulator of aging in C. elegans, depending on bacterial diet. FLR-4 functions to prevent differential activation of the p38MAPK pathway in response to diverse food-types, thereby maintaining normal life span. In a kinase-dead flr-4 mutant, E. coli HT115 (K12 strain), but not the standard diet OP50 (B strain), is able to activate p38MAPK, elevate expression of cytoprotective genes through the nuclear hormone receptor NHR-8 and enhance life span. Interestingly, flr-4 and dietary restriction utilize similar pathways for longevity assurance, suggesting cross-talks between cellular modules that respond to diet quality and quantity. Together, our study discovers a new C. elegans gene-diet pair that controls the plasticity of aging.

On the basis of multiple experiments demonstrating that high resistance to stress is associated with long lifespan, it has been proposed that stress resistance is a key determinant of longevity. However, the extent to which high resistance to stress is necessary or sufficient for long life is currently unclear. In this work, we use a genetic approach to disrupt different stress response pathways and examine the resulting effect on the longevity of the long-lived insulin-like growth factor 1 (IGF1) receptor mutant daf-2. Although mutation of the heat shock factor gene hsf-1, deletion of sod genes, deletion of the p38 MAPK kinase gene pmk-1, or deletion of the transcription factor gene egl-27 all resulted in decreased resistance to at least one form of stress and decreased lifespan, the magnitude of change in stress resistance did not correspond to the magnitude of change in lifespan. In addition, we found that deletion of the glycerol-3-phosphate dehydrogenase genes gpdh-1 and gpdh-2 or deletion of the DAF-16 cofactor gene nhl-1 also results in decreased resistance to at least one form of stress but increases lifespan. Overall, our results suggest that while increased stress resistance is associated with longevity, stress resistance, and lifespan can be experimentally dissociated.