The old guard: Age-related changes in microglia and their consequences
The old guard: Age-related changes in microglia and their consequences
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DOI：
10.1016/j.mad.2021.111512
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发表时间：
2021-05-26
影响因子：
5.3
通讯作者：
Cardoso, Ana L.
中科院分区：
文献类型：
--
作者：
Costa, Jessica;Martins, Solange;Cardoso, Ana L.
在所有主要器官中，大脑是最容易受到衰老无情影响的器官之一。在过去的几十年里，在人类群体和动物模型中进行的几项研究表明，大脑中存在大量与年龄相关的变化，包括神经发生减少、氧化损伤、线粒体功能障碍和细胞衰老。作为神经组织的主要免疫效应器和第一反应者，小胶质细胞处于这些事件的中心。这些细胞经历了不可逆转的变化，由于长期暴露于环境触发因素，如压力，感染和代谢失调。小胶质细胞获得的年龄相关的免疫衰老表型的特征是其转录组谱、分泌组、形态和吞噬活性的深刻改变，这损害了它们的内护和防御功能。因此，衰老的小胶质细胞不再能够建立有效的免疫反应和维持正常的突触活动，直接导致与年龄相关的认知能力下降和神经退行性变。这篇综述讨论了生活方式和环境因素如何在分子和功能水平上驱动小胶质细胞功能障碍，也强调了可能的干预措施来逆转与衰老相关的神经和免疫系统损伤。
Among all major organs, the brain is one of the most susceptible to the inexorable effects of aging. Throughout the last decades, several studies in human cohorts and animal models have revealed a plethora of age-related changes in the brain, including reduced neurogenesis, oxidative damage, mitochondrial dysfunction and cell senescence. As the main immune effectors and first responders of the nervous tissue, microglia are at the center of these events. These cells experience irrevocable changes as a result from cumulative exposure to environmental triggers, such as stress, infection and metabolic dysregulation. The age-related immunosenescent phenotype acquired by microglia is characterized by profound modifications in their transcriptomic profile, secretome, morphology and phagocytic activity, which compromise both their housekeeping and defensive functions. As a result, aged microglia are no longer capable of establishing effective immune responses and sustaining normal synaptic activity, directly contributing to age-associated cognitive decline and neurodegeneration. This review discusses how lifestyle and environmental factors drive microglia dysfunction at the molecular and functional level, also highlighting possible interventions to reverse aging-associated damage to the nervous and immune systems.