The endoplasmic reticulum (ER) plays a key role in the regulation of protein folding, lipid synthesis, calcium homeostasis, and serves as a primary site of sphingolipid biosynthesis. ER stress (ER dysfunction) participates in the development of mitochondrial dysfunction during aging. Mitochondria are in close contact with the ER through shared mitochondria associated membranes (MAM). Alteration of sphingolipids contributes to mitochondria-driven cell injury. Cardiolipin is a phospholipid that is critical to maintain enzyme activity in the electron transport chain. The aim of the current study was to characterize the changes in sphingolipids and cardiolipin in ER, MAM, and mitochondria during the progression of aging in young (3 mo.), middle (18 mo.), and aged (24 mo.) C57Bl/6 mouse hearts. ER stress increased in hearts from 18 mo. mice and mice exhibited mitochondrial dysfunction by 24 mo. Hearts were pooled to isolate ER, MAM, and subsarcolemmal mitochondria (SSM). LC-MS/MS quantification of lipid content showed that aging increased ceramide content in ER and MAM. In addition, the contents of sphingomyelin and monohexosylceramides are also increased in the ER from aged mice. Aging increased the total cardiolipin content in the ER. Aging did not alter the total cardiolipin content in mitochondria or MAM yet altered the composition of cardiolipin with aging in line with increased oxidative stress compared to young mice. These results indicate that alteration of sphingolipids can contribute to the ER stress and mitochondrial dysfunction that occurs during aging.

内质网（ER）在蛋白质折叠、脂质合成、钙稳态的调节中发挥着关键作用，并且是鞘脂生物合成的主要场所。内质网应激（ER 功能障碍）参与衰老过程中线粒体功能障碍的发生。线粒体通过共享的线粒体相关膜（MAM）与内质网密切接触。鞘脂的改变会导致线粒体驱动的细胞损伤。心磷脂是一种磷脂电子传递链中的酶活性至关重要。本研究的目的是表征年轻（3 个月）、中年（18 个月）和老年（24 个月）C57Bl 衰老过程中 ER、MAM 和线粒体中鞘脂和心磷脂的变化。 /6 老鼠心。从 18 个月开始，心脏的 ER 压力增加。小鼠和小鼠在 24 个月时表现出线粒体功能障碍。合并心脏以分离 ER、MAM 和肌膜下线粒体 (SSM)。脂质含量的 LC-MS/MS 定量表明，衰老会增加ER 和 MAM 中的神经酰胺含量。此外，老年小鼠内质网中鞘磷脂和单己糖神经酰胺的含量也有所增加。衰老增加了内质网中心磷脂的总含量。与年轻小鼠相比，衰老并没有改变线粒体或MAM中的总心磷脂含量，但随着氧化应激的增加，心磷脂的组成发生了变化。这些结果表明，鞘脂的改变可能会导致衰老过程中发生的内质网应激和线粒体功能障碍。