Abstract

Recent studies have revealed that different classes of lipids play essential roles in the intrinsically complex process of cellular aging. Although these roles of lipids is blurred by intricacy and complexity, the identification of mechanisms that link lipid metabolism to cellular aging is currently underway. The investigation of a cell’s entry into and progression through a differentiated quiescent state can provide a means of linking cell cycle regulation to aging. Using yeast Saccharomyces cerevisiae as a model organism, I explored how the major lipid classes phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylserine (PS), as well as mitochondria specific cardiolipin (CL) and major storage lipid triacylglycerol (TAG), are influenced during the aging process by various dietary, pharmacological and genetic interventions known to extend longevity. These interventions include a caloric restriction diet, lithocholic bile acid (LCA) and the tor1Δ mutation eliminating the key protein component of the pro-aging Target of Rapamycin Complex 1 (TORC1) pathway. The quantitation of different lipid classes throughout the entire lifespan was accomplished by the mass spectrometric analysis of lipids found in quiescent and non-quiescent cell populations separated by centrifugation in a Percoll density gradient. My findings revealed that there are at least three different ways of delaying aging in yeast by differently altering lipid metabolism and transport in chronologically aging cells.