Immunometabolic regulation of bone inflammaging

项目总结 老年人多器官的年龄相关性炎症和异位脂质堆积与骨骼相关 失落、虚弱和慢性病。例如，骨骼和胸腺是主要的主要淋巴器官， 在人类和小鼠模型中逐渐积累异位脂肪和脂肪细胞。富有同情心的 神经系统(SNS)通过突触后局部释放儿茶酚胺来调节所有器官系统 在没有完成控制转录的事件所需的时间延迟的情况下快速地形成小泡 特定细胞因子或脂肪因子的激活或翻译后调节。释放的儿茶酚胺 来自SNS的各种局部组织中的缝隙是脂肪酸氧化所必需的，这一过程在老年人中受到损害。 这项提案旨在解决的关键问题是：a)衰老如何导致异位脂质在 骨髓?B)异位脂质的增加是否是骨增加的关联触发因素 衰老过程中出现的炎症和骨质疏松。C)是否可以防止骨丢失和异位堆积 通过瞄准连接免疫-代谢串扰的机制来衰老？这些问题源于我们的 发现衰老与去甲肾上腺素(NE)的降解增加有关 儿茶酚胺降解酶单胺氧化酶A的表达的长期目标是 该项目旨在破译控制骨炎的神经免疫串扰，并以此为目标。 机制，以开发新的方法，以维持或增强老年人的骨功能。

PROJECT SUMMARY Age-related inflammation and accumulation of ectopic lipid in multiple organs in elderly is associated with bone loss, frailty and chronic diseases. For example, bone and thymus are the major primary lymphoid organs that progressively accumulate ectopic lipid and adipocytes in humans and mouse models. The sympathetic nervous system (SNS) regulates all organ systems by localized release of catecholamines from post-synaptic vesicles in a rapid fashion without the time-lag required to complete events that control transcriptional activation or post-translational regulation of specific cytokines or adipokines. The catecholamines released from SNS in various local tissue niches is required for fatty acid oxidation, a process that is impaired in elderly. The key questions this proposal aims to address is: A) How does aging cause accumulation of ectopic lipid in bone marrow? B) Whether increase in ectopic lipid serves as an associative trigger for increase in bone inflammation and osteoporosis seen during aging. C) Can one prevent bone loss and ectopic accumulation in aging by targeting the mechanisms that link immune-metabolic crosstalk? These questions emanate from our discovery that aging is associated with increased degradation of norepinephrine (NE) due to elevated expression of Monoamine Oxidase A (MAOA), a catecholamine degradation enzyme. The long-term goal of this project is to decipher neuro-immune crosstalk that controls bone inflammation and to target this mechanism to develop new approaches to maintain or enhance bone function in elderly.