Triacylglycerol (TAG) is one of the fundamental molecules of life that exists in all living organisms. TAG is a non-polar lipid which has a role in controlling cellular energy stockpiles, lipid homeostasis, and cellular signaling. Conventional thought holds that cells accumulate TAG only when they consume excess energy, but a growing body of research reveals that TAG accumulation also takes place when cells are exposed to stresses. This suggests a potential life-preserving role for TAG. Our studies have discovered that high accumulation of intracellular TAG in budding yeast, S. cerevisiae, correlates with extended chronological lifespan. In general, wild yeast exhibit larger volumes of TAG and significantly longer lifespans than laboratory yeast. Additionally, increasing intracellular TAG levels in laboratory strains by either abolishing TAG lipases or enhancing TAG biosynthesis results in lifespan extension, whereas blocking TAG production leads to premature aging.The TAG-associated lifespan mechanism is unlikely dependent on several well- characterized longevity pathways such as the Target-of-Rapamysin (TOR) and the RAS/ PKA pathways. While TAG accumulation does not protect cells from stresses such as UV light, osmolarity, and acidity, our data suggest that high-TAG yeast may benefit fromdecreased reactive oxygen species (ROS) or increased resistance to oxidative damages. In order to quantitatively measure ROS level in yeast cells, we have developed a normalization technique that is applicable to aging studies via using the fluorescent probe, 2’,7' -dichlorofluorescein diacetate. The results demonstrate that yeast with high TAG abundance display lower intracellular ROS than that of wild-type yeast. On the other hand, yeast with low TAG exhibit significantly increased ROS and oxidative damages. These results support the mitochondrial free radical theory of aging which suggests that longevity can be extended by reducing cell injury from ROS. Subsequently, we offer the radical sink hypothesis proposing a TAG-mediated longevity mechanism by which TAG can intercept ROS before they impair other vital macromolecules and then safely transfer to lipid droplets.Because TAG metabolism and most lifespan regulations are highly conserved from yeast to human, it is possible that this lifespan regulation can universally apply to other organisms. It is important to note that these results are consistent with an observation in modern societies called obesity paradox, a phenomenon by which overweight individuals benefit from lower overall mortality rate than normal or underweight people. Our findings thus demonstrate an overlooked function of TAG that could potentially readjust future healthcare guidelines in order to increase greater a healthy life of the advanced age.
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