Session: Advances in Mass Spectrometry:

The endogenous levels of specific cytochrome P450 (CYP) polyunsaturated fatty acids (PUFAs) metabolites correlate with the disease progression in many animal models, including diabetes, neuropathy, hypertension, cancer, and neurodegenerative diseases. The risk of the diseases mentioned above increases with aging. Therefore, in this study, we will specifically determine the effect of aging on the CYP metabolism of PUFAs and investigate the relationship between CYP PUFA metabolites’ levels and age-associated neuronal functional decline. We hypothesize that aging affects CYP PUFA metabolism.
In this regard, we will use C. elegans as a model organism in our study owing to its long history of being used to investigate aging. The corresponding findings have been translated to mammals and humans, like the inference of insulin signaling and calorie restriction in aging. Furthermore, the short half-life, the ease of handling, and vast genetic tools availability greatly facilitate the aging study in C. elegans. Also, the aging pathways and neuronal structure in C. elegans are conserved in humans.
In this study, we will develop analytical tools to measure the endogenous levels of CYP PUFA metabolites over the lifespan of C. elegans using state-of-the-art ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). These metabolites are very potent but present in low abundance. The dramatic increase in sensitivity in UPLC-MS/MS allows us to monitor these metabolites over the lifespan of C. elegans with minimum samples. In this presentation, we will show that C. elegans also produce very similar classes of CYP PUFA metabolites as mammals and humans using our preliminary SPE-UPLC-MS/MS method. We will also report that some CYP PUFA metabolites correlate with the lifespan and/or neuronal health of C. elegans. The results from this project will significantly improve our understanding of the role of dietary PUFAs and associated metabolism on aging and neurodegeneration and will uncover new mechanisms of how aging affects neurodegeneration through modulation of PUFA metabolic pathways.

Kin Sing Lee

Appearances