Sarparast, Morteza, Lee, Kin Sing Stephen, Dattmore, Devon, Alan, Jamie K., Kessler, Benjamin, Zhang, Fan
[
International Worm Meeting,
2021]
Specific omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have protective effects against aging-related conditions such as cardiovascular disease, inflammation, and neurodegenerative diseases. However, it is unclear which PUFAs are required in the diet and how they affect human health and disease. This study will investigate the physiological roles of individual PUFAs in order to pharmacologically and dietarily promote healthy aging. We will use fatty acid desaturase enzyme knockout transgenic C. elegans strains to assess the in vivo effects of PUFAs on the aging process. This investigation will create a dataset that includes lifespan and healthspan data (as determined by thrashing and/or egg laying) for every available fatty acid desaturase enzyme genetic knockout in the worm. Additionally, lipidomic or metabolic analysis will be used to assess the lipidome of key strains. We hypothesize that specific PUFAs modulate physiological processes through their corresponding downstream metabolites' role in lipid signaling. Our data showed that mutants with genetically disrupted PUFA biosynthesis displayed a decreased median lifespan, poor physical fitness, and altered egg laying patterns. Interestingly, our results from several mutants are different from published data involving the use of FuDR, a chemical that prevents progeny. It is expected that lipidomic analysis of the knockout worms will reveal that our in vivo observations are associated with an altered lipid panel, especially downstream metabolites. Our data suggest that genetically altering endogenous levels of PUFAs modulates lifespan and healthspan. However, specifically limiting omega-3 PUFA biosynthesis has a rescuing effect on healthspan. Investigating these metabolic pathways may elucidate novel drug targets that could revolutionize chronic disease treatment and prevention.