Centre for Cardiometabolic Research in Africa (CARMA), Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Parow, South Africa.
Adv Exp Med Biol. 2021;1286:225-250. doi: 10.1007/978-3-030-55035-6_16.
Aging is driven by four interlinked processes: (1) low-grade sterile inflammation; (2) macromolecular and organelle dysfunction, including DNA damage, telomere erosion, and mitochondrial dysfunction; (3) stem cell dysfunction; and (4) an accumulation of senescent cells in tissues. Adipose tissue is not immune to the effects of time, and all four of these processes contribute to a decline of adipose tissue function with advanced age. This decline is associated with an increase in metabolic disorders. Conversely, optimally functioning adipose tissue generates signals that promote longevity. As tissue-resident progenitor cells that actively participate in adipose tissue homeostasis and dysregulation, adipose stem cells (ASCs) have emerged as a key feature in the relationship between age and adipose tissue function. This review will give a mechanistic overview of the myriad ways in which age affects ASC function and, conversely, how ASC function contribute to healthspan and lifespan. A central mediator in this relationship is the degree of resilience of ASCs to maintain stemness into advanced age and the consequent preservation of adipose tissue function, in particular subcutaneous fat. The last sections of this review will discuss therapeutic options that target senescent ASCs to extend healthspan and lifespan, as well as ASC-based therapies that can be used to treat age-related pathologies, and collectively, these therapeutic applications may transform the way we age.
（1）低度无菌性炎症；（2）大分子和细胞器功能障碍，包括 DNA 损伤、端粒磨损和线粒体功能障碍；（3）干细胞功能障碍；（4）衰老细胞在组织中的积累。脂肪组织并不能免受时间的影响，这四个过程都导致随着年龄的增长脂肪组织功能下降。这种下降与代谢紊乱的增加有关。相反，功能最佳的脂肪组织会产生促进长寿的信号。脂肪干细胞（ASCs）作为组织驻留祖细胞，积极参与脂肪组织的动态平衡和失调，是年龄与脂肪组织功能关系中的一个关键特征。这篇综述将从机制上概述年龄如何影响 ASC 功能，以及 ASC 功能如何有助于健康寿命和寿命。在这种关系中，一个中心介质是 ASC 维持干性到老年的恢复力程度，以及随后对脂肪组织功能的保存，特别是皮下脂肪。这篇综述的最后部分将讨论针对衰老 ASC 的治疗选择，以延长健康寿命和寿命，以及基于 ASC 的治疗方法，可用于治疗与年龄相关的疾病，这些治疗应用可能会改变我们衰老的方式。
