### PRKAA1 Gene Overview

**Gene Symbol**: PRKAA1  
**Protein Function**: Catalytic subunit of AMP-activated protein kinase (AMPK)  
**Role**: Cellular energy sensor; regulates metabolism in response to AMP/ATP ratio changes.

### Additional Associations

1. **Associated Genes**: 
   - **AMPK Complex Genes**: PRKAB1 (PRKAA1 regulatory subunit), PRKAB2
   - **Metabolic Enzymes**: ACACA, ACACB, GYS1, HMGCR, LIPE, IRS1, PFKFB2, PFKFB3, SLC2A4 (GLUT4), and others related to fatty acid and cholesterol metabolism.
   - **Transcription Factors**: CRTC2/TORC2, FOXO3, SREBF1, and SREBF2.

2. **Aging and Age-related Diseases**: 
   - **Aging**: AMPK activation has been linked to increased lifespan in various model organisms through its roles in metabolism and energy homeostasis.
   - **Age-related diseases**: Dysregulation of PRKAA1/AMPK is implicated in age-associated disorders such as:
     - **Type 2 Diabetes**: AMPK helps improve insulin sensitivity and glucose homeostasis.
     - **Neurodegenerative Diseases**: AMPK activity may mitigate effects of neurodegeneration seen in Alzheimer’s disease and other age-related cognitive decline.
   - **Cancer**: AMPK serves as a tumor suppressor; its activation can hinder cell proliferation and growth in cancer cells.

3. **Drug Interactions**:
   - **Adenosine analogs**: Compounds that increase AMP levels can activate AMPK indirectly.
   - **Metformin**: An antidiabetic drug that activates AMPK, enhancing insulin sensitivity and glucose uptake.
   - **Berberine**: An herbal supplement that activates AMPK and has been shown to have metabolism-regulating effects.
   - **AICAR** (5-Aminoimidazole-4-carboxamide ribonucleotide): A compound that stimulates AMPK activation.
   - **Resveratrol**: Found in red wine; it can activate AMPK and has been studied for its potential anti-aging effects.

4. **Pathways and Biological Processes**:
   - **AMPK Signaling Pathway**: Central for regulating energy metabolism, glucose uptake, and biosynthetic pathways.
   - **Insulin Signaling**: Enhances the insulin pathway in response to nutrient status.
   - **mTOR Signaling**: Inhibits the mTORC1 complex in response to nutrient scarcity; affects cellular growth and autophagy.
   - **Lipid Metabolism**: Regulates enzymes involved in fatty acid synthesis and lipolysis.
   - **Autophagy**: Promotes cellular clearance through activation of autophagy pathways.
   - **Hypoxia Response**: AMPK activation aids in cellular survival under low-oxygen conditions.
   - **Cell Cycle Regulation**: Inhibits cellular proliferation pathways under energy deprivation.
   - **Chromatin Remodeling**: Phosphorylation of histones and transcription factors involved in metabolic regulation.

Through its multiple roles and interactions, PRKAA1 is a critical gene for maintaining energy balance in the cell and has far-reaching implications for metabolic diseases, aging, and potential therapeutic targets.