Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.

Abstract

Astrocytes, the most abundant glial cells in the central nervous system, play increasingly recognized roles in metabolic regulation beyond their classical supportive functions. This review summarizes current understanding of astrocyte morphological and molecular heterogeneity, with emphasis on regional metabolic properties across different brain areas. We discuss the primary forms and functional significance of astrocyte-neuron metabolic coupling, focusing on glucose, lipid, and glutamate metabolism, lactate shuttling, as well as the mitochondrial reactive oxygen species signaling. Furthermore, we integrate emerging evidence from animal and preclinical studies linking astrocyte-neuron metabolic coupling to ageing-related diseases. Collectively, these findings highlight how astrocyte-neuron interactions sustain physiological homeostasis and contribute to pathological manifestations, underscoring their significance in both health and ageing-related diseases.