biostudies-literatureBastian CNational Institute of Neurological Disorders and StrokeNIA NIH HHSNINDS NIH HHSNational Institute on Aging114173https://www.ebi.ac.uk/biostudies/studies/S-EPMC11218845biostudies-literatureUnknown357The astrocyte-neuron lactate shuttle (ANLS) is an essential metabolic support system that uptakes glucose, stores it as glycogen in astrocytes, and provides glycogen-derived lactate for axonal function. Aging intrinsically increases the vulnerability of white matter (WM) to injury. Therefore, we investigated the regulation of this shuttle to understand vascular-glial metabolic coupling to support axonal function during aging in two different WM tracts. Aging astrocytes displayed larger cell bodies and thicker horizontal processes in contrast to thinner vertically oriented processes of young astrocytes. Aging axons recovered less following aglycemia in mouse optic nerves (MONs) compared to young axons, although providing lactate during aglycemia equally supported young and aging axonal funcExperimental neurologyAging astrocytes metabolically support aging axon function by proficiently regulating astrocyte-neuron lactate shuttle.PMC112188451R21NS094881R01 AG033720R56 AG033720R21 NS094881AG033720Faris AZerimech SBaltan SBastian CNguyen HQuinn JFranke CDoherty CfalseAging astrocytes metabolically support aging axon function by proficiently regulating astrocyte-neuron lactate shuttle.The astrocyte-neuron lactate shuttle (ANLS) is an essential metabolic support system that uptakes glucose, stores it as glycogen in astrocytes, and provides glycogen-derived lactate for axonal function. Aging intrinsically increases the vulnerability of white matter (WM) to injury. Therefore, we investigated the regulation of this shuttle to understand vascular-glial metabolic coupling to support axonal function during aging in two different WM tracts. Aging astrocytes displayed larger cell bodies and thicker horizontal processes in contrast to thinner vertically oriented processes of young astrocytes. Aging axons recovered less following aglycemia in mouse optic nerves (MONs) compared to young axons, although providing lactate during aglycemia equally supported young and aging axonal func2022-01-01T00:00:00Z2022 Nov2025-04-04T19:23:03.237Z2025-04-04T19:23:03.237ZS-EPMC112188453586350010.1016/j.expneurol.2022.114173