Considering the Gut Microbiome's Influence on Astrocytes in the Aging Brain
The influence of the gut microbiome on the long-term trajectory of health is a popular topic these days. Tools for assessing the microbial composition of the gut microbiome are accurate and cost little, and variance in the relative sizes of microbial populations between individuals and across a life span are increasingly correlated with effects on health, disease, and the pace of aging. Of particular interest are the ways in which the gut microbiome may be affecting the operation of the brain, such as via the generation of harmful inflammatory signaling, or the production of metabolites such as butyrate that can influence neurogenesis. Here, researchers focus specifically on connections between the gut microbiome and the supporting astrocyte cells of the brain, known to become dysfunction with age.
As the most abundant type of glial cells, astrocytes perform significant functions in neural activity regulation, synapse formation, neural metabolism, and blood-brain barrier (BBB) integrity and, therefore, maintain the normal physiological functions of the central nervous system (CNS). With continuous advancements in research, the roles of astrocytes in aging and neurodegenerative diseases (NDs) have started to receive scientific attention. There is a loss of morphological structure in star-shaped astrocytes with brain aging that can lead to a decline in their functionality, such as reduced astrocytic synaptic coverage, fewer aquaporin 4 (AQP4) channels expressed in astroglial end-feet followed by decreased lymphatic clearance, compromised BBB integrity, inadequate clearance of glutamate and potassium ions, and impaired energy metabolism. Additionally, with advancing age, and in the context of NDs, reactive astrocytes and aged astrocytes gradually accumulate, triggering neuroinflammation and having detrimental impacts on the tissue microenvironment, and ultimately leading to age-related cognitive decline.
Over the past decade, the roles of the intestinal microbiota in regulating the gut-brain axis and its involvement in the pathophysiology of brain aging have become increasingly emphasized. A previous study has shown that the gut microbiota is an important upstream factor in astrocyte activation, which is closely associated with neuroinflammation and neurodegeneration. Thus, a deeper comprehension of the roles and mechanisms of the gut microbiota-astrocyte axis in age-related cognitive decline is becoming ever more necessary and meaningful. This review aims to elucidate and summarize the unique changes to gut microbiomes seen during the process of aging, alterations in the shape and function of astrocytes within the aging brain, and potential mechanisms, such as the vagus nerve, immune responses, the circadian rhythm, and microbial metabolites, by which gut microbiomes influence cognitive function by impacting CNS astrocyte activity. In this way, we aim to provide new insights into therapeutic avenues for age-related cognitive decline.