A novel gene-diet pair modulates C. elegans aging

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.
Author summary For animals living in the wild, being able to utilize a wide range of diet is evolutionarily advantageous as they can survive even when their optimal diet is depleted. Since diet is known to influence the rate of aging, animals seem to have evolved intricate mechanisms to maintain homeostasis and normal life span, but the molecular mechanisms are less understood. Using a small nematode, C. elegans as a model, we show that the adaptive capacity to different diet is maintained by a kinase gene. When this gene is mutated, worms start living longer on one strain of bacterial diet but not on the other. We identify the molecular cascade required for this food-type-dependent longevity. We show that this cascade of events significantly overlaps with the pathway that determine food quantity-dependent life span enhancement. Our study thus elucidates a part of the molecular monitoring system that regulates longevity dependent on the available quality and quantity of diet.