Molecular mechanisms of intra- and inter-cellular fatty acid trafficking

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ABSTRACT The biological hallmarks of aging have outlined multiple cellular and molecular processes that contribute to aging. The hallmarks of aging include genomic instability; telomere attrition; epigenetic alterations; loss of proteostasis; deregulated nutrient sensing; mitochondrial dysfunction; cellular senescence; stem cell exhaustion; and altered intercellular communication. These processes have been studied primarily in isolation from each other. However, many of these processes span multiple cellular organelles or occur at the intersection between organelles. We will use multispectral imaging to systematically investigate the morphology and dynamics of six organelles simultaneously in live cells, as a method for imaging organelle communication in relation to the hallmarks of aging. The organelles we will image include endoplasmic reticulum, Golgi, lysosomes, mitochondria, peroxisomes, and lipid droplets. In aim 1, we will quantify organelle number, size, shape, speed, contacts with other organelles, and distribution (the “organelle signature”), in multiple cell types at baseline. In aim 2, we will test how organelle morphodynamics change during replicative aging. Together, these studies will identify novel forms of organelle communication impacting the hallmarks of aging.