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

摘要 衰老的生物学标志概述了多种细胞和分子过程， 有助于衰老。衰老的标志包括基因组的不稳定性、端粒的磨损、 表观遗传改变;蛋白质稳态丧失;营养感应失调;线粒体 功能障碍;细胞衰老;干细胞耗竭;和改变的细胞间通讯。 这些过程主要是相互孤立地研究的。但许多 这些过程跨越多个细胞器或发生在 细胞器我们将使用多光谱成像系统地研究形态学， 活细胞中六个细胞器同时动态，作为细胞器成像的方法 沟通与衰老的标志有关。我们将成像的细胞器包括 内质网、高尔基体、溶酶体、线粒体、过氧化物酶体和脂滴。在aim中 1，我们将量化细胞器的数量，大小，形状，速度，与其他细胞器的接触， 在基线时，在多种细胞类型中的细胞器分布（“细胞器特征”）。在目标2中，我们将测试 细胞器形态动力学在复制性衰老过程中如何变化。这些研究将 识别影响衰老标志的细胞器通信的新形式。

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.