Astrocytes in maintaining neuronal health and brain function: interplay of aging, diet, and environment.

Abstract

Astrocytes are pivotal modulators of neuronal health and brain function through their roles in metabolic support, synaptic regulation, neurotransmitter recycling, and the maintenance of the blood-brain barrier. However, aging and environmental challenges compromise astrocytic function, setting the stage for neurodegeneration. Recent findings reveal that age-related astrocyte senescence-characterized by mitochondrial decline, structural atrophy, and a pro-inflammatory shift-undermines their capacity to support neurons, leading to cognitive decline and neurodegenerative conditions such as Alzheimer's disease. Environmental factors, notably dietary influences, further modulate astrocytic behavior. High-fat diets may initially enhance aspects of astrocytic function, such as glutamate clearance; yet prolonged exposure often triggers maladaptive metabolic shifts and neuroinflammation. In contrast, caloric restriction promotes metabolic flexibility and exerts anti-inflammatory effects, thereby preserving astrocytic integrity. Sleep also plays a crucial role by facilitating glymphatic clearance and synaptic maintenance, whereas sleep deprivation disrupts calcium signaling and exacerbates inflammatory processes. This review synthesizes recent advances in the metabolic, immune, and intercellular mechanisms underlying astrocytic dysfunction in aging. By integrating these insights, we highlight the therapeutic potential of targeting astrocyte-mediated processes to preserve cognitive resilience and counteract neurodegeneration.