Identification of Neurosensory Systems for Nutrient Evaluation and Their Regulatory Roles on Physiology and Lifespan.

[摘要] Across taxa, exposure to a reduced-nutrient diet without malnutrition, or dietary restriction (DR), delays the onset and progression of physiological and behavioral decline over time. Interestingly, research using the nematode, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has revealed that exposure to food odors is sufficient to limit the benefits of DR on lifespan, suggesting an evolutionarily conserved role for sensory perception on aging. However, knowledge about how sensory information is processed or how it initiates widespread changes in physiology, including aging, remains rudimentary. I hypothesized that neuronal processes that are involved in sensing and evaluating key longevity-modulating nutrients are potent regulators of organismal health and diet-mediated lifespan. I first aimed to understand how one of the key-longevity modulating nutrients, dietary protein, is perceived and initiates widespread changes in physiology. I found that the fruit fly exhibits a transient feeding preference for protein-containing food after modest starvation. I discovered that serotonergic signaling mitigates protein demand by modulating reward associate with protein intake. Moreover, reduced serotonin synthesis or loss of 5HT2a nearly doubled fly lifespan when the animals were maintained in a complex nutritional environment. This suggests a process of nutrient evaluation itself impacts aging. I then aimed to investigate a role of nutrient perception on other aspects of health. Sleep loss in fruit fly is a characteristic response to nutrient deprivation. Because sleep loss is costly to the organism, mechanisms for evaluating the nutrient environment and quickly terminating this behavioral response when food is available would likely to be beneficial. I leveraged this phenotype to discover that perception of sweet taste is sufficient to change the course of behavioral decision from foraging to sleep and dopaminergic circuits in part modulate this behavioral switch. Together my work provides important insights into how nutrients interact with nutrient states of animals and which neurological systems are involved in such interactions. I believe results from my study provides basic framework to examine how nutrient signals are processed in more complex organisms and fosters clinical research to target neurological regulation of nutrient intake or age-associated disease progression.

[发布机构] University of Michigan

[效力级别] Physiology

[关键词] Serotonin modulate diet-dependent lifespan;Physiology;Health Sciences;Cellular and Molecular Biology