Abstract

A collaboration between the Titorenko laboratory and Idunn Technologies Inc. has led to a recent discovery of 14 plant extracts that delay the chronological mode of aging in the budding yeast Saccharomyces cerevisiae. Age-related changes in the abundance of lipid droplets, a site for the deposition and lipolytic degradation of the neutral lipids triacylglycerols and steryl esters, are known to play essential roles in defining yeast longevity. Therefore, one objective of my thesis was to investigate how each of the 14 aging-delaying plant extracts influences the number and size of lipid droplets at different stages of yeast chronological aging. I found that 8 of 14 plant extracts delay yeast chronological aging not because they alter the number of droplets or change their size. Because the number and size of lipid droplets are known to be defined by the relative rates of neutral lipid synthesis in the endoplasmic reticulum, neutral lipid deposition in lipid droplets, neutral lipid lipolytic degradation in lipid droplets, fusion of lipid droplets and fragmentation of lipid droplets, I concluded that the aging-delaying effects of these 8 plant extracts in yeast are unlikely to be caused by changes in the relative rates of the above cellular processes. I also found that 6 of 14 aging-delaying plant extracts cause changes in the number or size of lipid droplets only on one or two (out of four) days of cell collection, each corresponding to different stages of the aging process. These findings suggest that such changes in lipid droplets abundance may (or may not) play essential roles in the ability of some (or all) of these 6 plant extracts to delay yeast chronological aging. To address this, further experiments are required. Because the synthesis,
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storage and degradation of neutral lipids are integrated into metabolic pathways for other lipid classes, I then used a combination of liquid chromatography and mass spectrometry to examine how 2 of the aging-delaying plant extracts that increase the size of lipid droplets without affecting their number affect the intracellular concentrations of several classes of lipids in chronologically aging S. cerevisiae. I found that these 2 aging-delaying plant extracts exhibit different and statistically significant effects on the concentrations of phosphatidylinositol phospholipids, triacylglycerols and free fatty acids. I therefore concluded that there may be 2 different ways of remodeling lipid metabolism in response to 2 different aging-delaying plant extracts. Future studies will test if such specific remodeling of lipid metabolism plays a causal role in the ability of each of these plant extracts to delay chronological aging of S. cerevisiae.