Aging astrocytes metabolically support aging axon function by proficiently regulating astrocyte-neuron lactate...

Area of Science:

• Neuroscience
• Cellular Metabolism
• Aging Research

Background:

• Aging compromises white matter (WM) integrity and function.
• The astrocyte-neuron lactate shuttle (ANLS) is crucial for neuronal energy supply.
• Understanding ANLS regulation in aging WM is vital for neuroprotection.

Purpose of the Study:

• Investigate ANLS regulation in aging WM.
• Determine how vascular-glial metabolic coupling supports axonal function during aging.
• Compare ANLS function in different WM tracts (optic nerve vs. corpus callosum).

Main Methods:

• Examined astrocyte morphology in young vs. aging mice.
• Assessed axonal function recovery after aglycemia (glucose deprivation).
• Evaluated the effects of exogenous lactate and high glucose on axonal function.

Main Results:

• Aging astrocytes exhibit altered morphology.
• Aging axons show impaired recovery from aglycemia, but lactate supplementation rescues function.
• High glucose pre-incubation enhances resilience to aglycemia in both young and aging axons.
• Corpus callosum axons demonstrate greater resilience to aglycemia than optic nerve axons.

Conclusions:

• Lactate serves as a universal axonal energy substrate, independent of age and myelination status.
• The ANLS plays a critical role in maintaining axonal function throughout aging.
• WM tract composition influences resilience to metabolic stress.