Research Paper Volume 15, Issue 19 pp 9896—9912

Figure 5. KEGG pathway enrichment of differential hub genes reveals that the aged neuron displays energetic deficit, dysfunctional neurotransmission, decreased branched-chain amino acid degradation and utilization of ketone bodies, and decreased one-carbon pool levels. KEGG pathway enrichment of differential hub genes was followed by manual curation of associated genes. The results are shown for neurotransmission (top panel) and aging (bottom panel). Oxidative phosphorylation (OxPhos, blue): high OxPhos levels during neurotransmission (A) but low OxPhos levels during aging (A’). Synaptic transmission: upregulated Na/K-ATPase pumps (orange) and glutamate synthesis (green) suggest active re-establishment of cation gradients (B) and high glutamate levels (C). The opposite was observed during aging (B’, C’). 3) Ketone body metabolism (yellow): decreased synthesis and increased degradation/utilization during neurotransmission (D), with the opposite observed during aging (D’). 4) Branched-chain amino acid (BCAA) degradation (purple): while differential hub genes involved in the degradation of BCAA were found downregulated during both neurotransmission (E) and aging (E’), dld, which encodes for a subunit of BCAA-decarboxylase, an early step in the degradation of all three BCAA was only downregulated during brain aging. 5) One carbon pool (pink): differential hub gene expression associated with one-carbon metabolism suggests high levels of one-carbon pool intermediates during neurotransmission (F) but low during aging (F’). Created with https://www.biorender.com/.