Polyunsaturated Fatty Acids in Membrane Dynamics of Aging C. elegans

Changes in membrane structure have been implicated in aging and age-related diseases. Specifically, the levels of polyunsaturated fatty acids (PUFAs), integral membrane components, have been shown to decrease over aging. The depletion of PUFAs is thought to result from their exceptional susceptibility to reactive oxygen species. Because oxidized PUFAs can then damage other lipids as well as DNA and proteins, the membrane pacemaker theory of aging states that PUFA abundance in the membrane is a key determinant of aging. In order to determine how PUFAs are lost over aging, we are utilizing stable isotope labeling in C. elegans to quantify fatty acid turnover throughout aging. Using metabolic flux analysis, we have found that the turnover of saturated and monounsaturated species decrease dramatically over aging suggesting that reduced membrane repair may cause PUFA loss. Due to new protocols, we are now able to study the dynamic flux in the PUFAs directly. Consistent with this hypothesis, we have found that PUFAs are not being replaced at the same rate over aging, implicating that these fatty acids are remaining in the membrane in a damaged state or saturated fatty acids are being incorporated aberrantly. While it is clear that the rate of fatty acid turnover is reduced, it is important to further define how this reduction impacts the membrane as well as the lifespan of the animal. In order to do this, we are supplementing diet with various PUFAs to study how each is utilized and maintained within the membrane upon uptake.