Research Paper Volume 15, Issue 19 pp 9896—9912

Figure 6. KEGG pathway enrichment analysis of astrocyte differential hub genes suggests a metabolic switch from aerobic glycolysis to oxidative phosphorylation during aging. (A and A’) Metabolic switch (blue): upregulation of ldha during neurotransmission but ldhb during aging. Ldha/b genes encode for subunits of lactate dehydrogenase, which catalyzes the interconversion of pyruvate into lactate. Ldha subunits favor lactate levels and were upregulated during neurotransmission, while ldhb favors pyruvate and is upregulated during aging. Also, the major glucose uptake transporter in the blood-brain barrier, encoded by slc2a1, was upregulated during neurotransmission only. Instead, during aging, mdh1/2 encode for enzymes of the malate-aspartate shuttle, which allows transport of NADH into the mitochondrial matrix to provide electrons for the ETC. Both genes were upregulated during aging, in agreement with a high OxPhos rate. (B and B’) Branched-chain amino acid (BCAA) degradation (purple): during neurotransmission, upregulation of slc7a5 was observed (amino acid transporter present in the cell surface and lysosome; participates in leucine uptake into the lysosome for degradation), while during aging, three enzymes involved in BCAA degradation, including dld, were downregulated. (C) Ketone body degradation/utilization (yellow): the enzyme encoded by bdh1 catalyzes the interconversion of acetoacetate and β-hydroxybutyrate, the two main ketone bodies, and was upregulated during aging only. (D) Synaptic transmission (green): abat encodes for an enzyme that breaks down GABA into glutamate and is downregulated during aging in the astrocyte. (E) One carbon pool (pink): differential hub gene expression associated with one-carbon metabolism suggests an increase in one-carbon pool during astrocyte aging. Created with https://www.biorender.com/.