The lipid composition of an animal?s membranes may be ultimately responsible for dictating its maximum lifespan. The potential role of membrane composition in aging is due to the variable susceptibility of different fatty acids to damage; therefore, the types of fatty acids within a membrane mandate its vulnerability to peroxidation. Furthermore, the membrane?s integrity is heavily influenced by its capacity to remove or repair damage; however, little is known about how membrane maintenance mechanisms impact membrane composition over aging. Using stable isotope tracers in C. elegans, we have quantified significant fatty acid replacement in the total phospholipid population, indicating that the membrane needs a continual infusion of new lipids for replacement of consumed and/or damaged molecules. We have found that over aging, the amount of resources funneled to phospholipids is dramatically reduced, which we hypothesize contributes to the altered membrane makeup seen in aged animals. Here, we aim to use stable isotopes to define the pathways that maintain the appropriate membrane composition in young animals and the genes that sense and respond to oxidized lipids. We will then use the identified regulators as well as lipid supplementation approaches to restore membrane composition and test for improved health and lifespan. These experiments will allow us to lay a framework to further understand how membrane fatty acid composition influences aging and ultimately define whether that relationship is causal or correlative.
The composition of a membrane is different in old animals than in young animals. Because it is known that the makeup of the membrane has an impact on its function, these age-related changes may contribute to aging and aging-related diseases like Alzheimer?s. Here, we propose to use the model nematode, C. elegans, to directly test how membrane structure impacts aging through the use of supplementation studies and mass spectrometry.
