The roles of sphingolipids in stress response and healthy aging.

Juniata College, Huntingdon PA

Investigators

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Abstract

? DESCRIPTION (provided by applicant): While lifespans are increasing, so is the age-related loss of cardiovascular, immune and cognitive functions. It is necessary to better understand aging biology so that the scientific community can promote health span, or the number of years one remains healthy and free of age-related disorders. In particular, aging animals exhibit poor stress response, which accelerates aging. This project examines the role of a bioactive lipid pathway - sphingolipid signaling - on oxidative stress responses using C. elegans. First, this project examines a panel of sphingolipid metabolism mutants on lifespan and survival to oxidative stress, using behavioral and cellular experiments. In particular, the proposal examines whether one particular sphingolipid, sphingosine-1-phosphate (S1P), can promote improved stress response and healthy aging. Secondly, the project examines how sphingolipids mediate bacteria-host interactions; specifically to stress induced by pathogenic bacteria. This aim uses lifespan and oxidative stress responses of animals to determine which sphingolipids may promote stress resilience in aging animals. Finally, this aim explores microbial gene expression dynamics in different host environments, including those of aging animals and animals lacking specific sphingolipid metabolism enzymes. Sphingolipids are major players in the intestinal tract; using mutants with altered sphingolipid signaling, metatranscriptomics analyses of how changes in host sphingolipids alter the gut microbiome may offer insights into mechanisms gut bacteria affect host aging. Together, the project aims to generate an invaluable dataset that interrelates host sphingolipids, the gut microbiome, and age to identify novel players in promoting healthy aging.