Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, United States.
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, United States; Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, 37232, United States; Vanderbilt Memory & Alzheimer's Center, Nashville, TN, 37212, United States; Vanderbilt Institute of Chemical Biology, Nashville, TN, 37232, United States; Vanderbilt Brain Institute, Nashville, TN, 37232, United States.
Mech Ageing Dev. 2020 Apr;187:111227. doi: 10.1016/j.mad.2020.111227. Epub 2020 Feb 29.
Aging globally effects cellular and organismal metabolism across a range of mammalian species, including humans and rabbits. Rabbits (Oryctolagus cuniculus are an attractive model system of aging due to their genetic similarity with humans and their short lifespans. This model can be used to understand metabolic changes in aging especially in major organs such as liver where we detected pronounced variations in fat metabolism, mitochondrial dysfunction, and protein degradation. Such changes in the liver are consistent across several mammalian species however in rabbits the downstream effects of these changes have not yet been explored. We have applied proteomics to study changes in the liver proteins from young, middle, and old age rabbits using a multiplexing cPILOT strategy. This resulted in the identification of 2,586 liver proteins, among which 45 proteins had significant p < 0.05) changes with aging. Seven proteins were differentially-expressed at all ages and include fatty acid binding protein, aldehyde dehydrogenase, enoyl-CoA hydratase, 3-hydroxyacyl CoA dehydrogenase, apolipoprotein C3, peroxisomal sarcosine oxidase, adhesion G-protein coupled receptor, and glutamate ionotropic receptor kinate. Insights to how alterations in metabolism affect protein expression in liver have been gained and demonstrate the utility of rabbit as a model of aging.
全球老龄化影响了多种哺乳动物物种的细胞和机体代谢,包括人类和兔子。兔子(Oryctolagus cuniculus)由于与人类的遗传相似性和较短的寿命,成为衰老研究的理想模型。该模型可用于研究衰老过程中的代谢变化,尤其是在肝脏等主要器官中,我们在肝脏中检测到脂肪代谢、线粒体功能障碍和蛋白质降解的明显变化。这种变化在几种哺乳动物中是一致的,但在兔子中,这些变化的下游影响尚未得到探索。我们应用蛋白质组学技术,通过多路复用 cPILOT 策略研究了年轻、中年和老年兔子肝脏蛋白的变化。这鉴定出了 2586 种肝脏蛋白,其中 45 种蛋白随衰老有显著变化(p < 0.05)。有 7 种蛋白在所有年龄段都有差异表达,包括脂肪酸结合蛋白、醛脱氢酶、烯酰辅酶 A 水合酶、3-羟酰基辅酶 A 脱氢酶、载脂蛋白 C3、过氧化物酶体肌氨酸氧化酶、黏附 G 蛋白偶联受体和谷氨酸离子型受体激酶。这些发现深入了解了代谢变化如何影响肝脏中的蛋白质表达,并证明了兔子作为衰老模型的实用性。