Astrocyte senescence: Evidence and significance

Abstract

Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central component of the age dependency of neurodegenerative disorders. Cumulative evidence supports an integral role of astrocytes in the initiation and progression of neurodegenerative disease and cognitive decline with aging. The loss of astrocyte function or the gain of neuroinflammatory function as a result of cellular senescence could have profound implications for the aging brain and neurodegenerative disorders, and we propose the term “astrosenescence” to describe this phenotype. This review summarizes the current evidence pertaining to astrocyte senescence from early evidence, in vitro characterization and relationship to age‐related neurodegenerative disease. We discuss the significance of targeting senescent astrocytes as a novel approach toward therapies for age‐associated neurodegenerative disease.

Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing

“…This is consistent with stereological findings that the number of glial cells increase with age in the frontal and temporal cortex (Terry et al, 1987). With age, glial cells, including astrocytes and microglia, change phenotype into a more pro-inflammatory state (Perry et al, 2007;Cohen and Torres, 2019). This increase in neuroinflammation may negatively impact cognitive function (Sartori et al, 2012).…”

A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease

“…Microglial cells play a key role in the immune surveillance of the presynaptic microenvironment and also for the synaptic remodeling toward axonal and dendritic terminals pruning by reshaping proteolytic and phagocytic processes. Microglial cells are able to recruit astroglia, or they can be recruited by the latter (30)(31)(32)35). They are thought to drive the well-known age-related regional synaptic vulnerability, as recently reported (36).…”

“…Astrocytes and microglia-the brain-resident macrophages-play a key role in neural circuit development and synaptic homeodynamics during adulthood. Astrocytes are essential for supporting synaptogenesis (axonal and dendritic spines sprouting) and regulating synaptic robustness (30)(31)(32). Astrocytes also contribute to the spatiotemporal integration of several synaptic signals and regulate the synaptic transmission (33,34).…”

Microglia and the aging brain: are senescent microglia the key to neurodegeneration?

“…However, such studies have largely focussed on abnormal glia behavior such as activation of microglia or the formation of astrocyte scars and the secretion of pro‐inflammatory cytokines (Liddelow ). However, there is increasing evidence that glia cells undergo an aging process and this may also impact neurodegenerative disease progression (Spittau ; Holtzman and Ulrich ; Cohen and Torres ). These glial cells can be described as either senescent or dystrophic (Streit et al ).…”