Functional categories/pathways altered with general aging and/or cognitive impairment
| NT | 5T | 21PT |
|---|---|---|
| Downregulated | ||
| Receptor tyrosine phosphatase (P) | AG patterns | AG patterns |
| Signal transduction (P) | Neurogenesis (P) | Cell surface receptor (P) |
| Myosin/actin binding (C, F) | Signal transducer/receptor (F) | Coated vesicle/synapse (P,C) |
| Transcription factor activity (F) | Ca2+ signaling (P) | Microtubule cytoskeleton/actin binding (C, F) |
| Axonal growth | Steroid/nuclear receptor (C) | Calcium ion binding (F) |
| Lipid uptake/synthesis | Axonal growth | Axonal growth |
| Lipid uptake/synthesis | Lipid uptake/synthesis | |
| Glucose oxidation | ||
| AI patterns | AI patterns | |
| G-protein-coupled receptors (P) | G-protein-coupled receptor/response to stimulus (P) | |
| Organogenesis (P) | ||
| IEG pathway | ||
| Shh/Wnt signaling | ||
| Lipogenesis | ||
| Glucose utilization | ||
| Insulin signaling | ||
| Upregulated | ||
| Immune response (P) | AG patterns | AG patterns |
| Ion homeostasis/ transport (P) | Immune response (P) | Immune response (P) |
| Lipid/protein metabolism/transport (β-oxidation) (P) | Ion homeostasis/transport (P) | Cell adhesion (P) |
| Lysosome (C) | Lipid/ protein metabolism/binding (β-oxidation) (P, F) | Neg. reg. transcrip. (P) |
| Growth factor activity (F) | Lysosome (C) | Lipid/protein metabolism (P) |
| Cholesterol transport (LXR) | Cholesterol transport (LXR) | Lysosome (C) |
| cAMP/PKA pathway | Cholesterol transport (LXR) | |
| TGF/BMP pathways | cAMP/PKA pathway | |
| Glycolysis | ||
| TGF/BMP pathways | ||
| AI patterns | AI patterns | |
| Oxidoreductase activity (F) | Activation of cell proliferation (P) | |
| Notch2 pathway | Organogenesis (P) | |
| Notch2 pathway | ||
| Myelinogenesis | ||
| AU patterns | AU patterns | |
| Receptor activity (P) | Hydrolase activity (F) | |
Gene categories are listed under each training condition by cognitive pattern and direction of change of most of their populating genes. Many of the categories listed under general aging (AG/NT) patterns (e.g., Axonal growth, Immune response) primarily comprised genes that were identified with AG/NT patterns under more than one training condition, whereas AI pattern pathways were more often identified under specific training conditions (e.g., IEGs at 5T). Categories/pathways with high proportions of coregulated genes were identified with EASE-based overrepresentation analysis of the Gene Ontology Database (P, Biological Process; C, Cell Component; F, Molecular Function) and by literature-based searches (boldface).