### Overview of PPARA Gene

**Gene Symbol:** PPARA  
**Gene Name:** Peroxisome proliferator-activated receptor alpha  
**Chromosomal Location:** Human chromosome 22

**Function:**  
The PPARA gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family, which plays a critical role as a nuclear receptor and transcription factor that regulates lipid metabolism, inflammatory response, and energy homeostasis. PPAR-alpha is activated by various ligands, including fatty acids and certain drugs, leading to the transcription of genes involved in fatty acid beta-oxidation, lipoprotein metabolism, and other processes related to lipid homeostasis.

### 1. Associated Genes

In addition to ACOX1 and members of the cytochrome P450 family (notably CYP4A and CYP4F), PPARA is known to interact with several other genes, including but not limited to:
- **ACSL (Acyl-CoA synthetases):** Involved in fatty acid activation for metabolism.
- **FABP (Fatty Acid Binding Proteins):** Important for transport and metabolism of fatty acids.
- **SCD (Stearoyl-CoA Desaturase):** Enzyme involved in fatty acid metabolism.
- **CPT1 (Carnitine palmitoyltransferase):** Plays a role in transporting fatty acids into mitochondria for beta-oxidation.

### 2. Aging and Age-related Diseases

Research indicates that PPARA is involved in several age-related processes. Notably:
- **Metabolic Dysregulation:** As organisms age, lipid metabolism may become dysregulated, and PPARA's role in maintaining lipid homeostasis has implications for age-associated metabolic disorders, such as dyslipidemia and obesity.
- **Inflammation:** PPARA influences pathways involved in inflammation. Chronic low-grade inflammation seen in aging (inflammaging) might be partially mitigated by PPARA's regulatory effects on immune cell function and inflammatory responses.
- **Neurodegenerative Diseases:** Some studies suggest associations between PPARA activity and neurodegenerative diseases, potentially through modulation of lipid metabolism in neuronal tissues and regulation of oxidative stress.

### 3. Drugs and Drug Classes Interacting with PPARA

Several drugs and drug classes are known to interact with PPARA, including:
- **Fibrates (e.g., Fenofibrate, Clofibrate):** These are hypolipidemic agents that act as PPAR-alpha agonists to reduce triglyceride levels and increase HDL cholesterol.
- **Thiazolidinediones (TZDs):** While primarily interacting with PPAR-gamma, they may also have effects on PPAR-alpha indirectly through metabolic pathways.
- **Omega-3 Fatty Acids:** Dietary supplements, particularly EPA and DHA, have been shown to activate PPARA.
- **Nuclear Hormone Receptor Modulators:** Substances that target nuclear hormone receptors may also exhibit some level of interaction with PPARA.

### 4. Involvement in Pathways and Biological Processes

PPARA is involved in numerous cellular processes and signaling pathways, including:
- **Fatty Acid Metabolism:** The regulation of genes involved in fatty acid beta-oxidation and degradation.
- **Lipid Homeostasis:** Control of lipoproteins and cholesterol levels.
- **Inflammatory Responses:** Participation in the modulation of pro-inflammatory cytokines and pathways.
- **Glucose Metabolism:** Influence on insulin sensitivity and glucose homeostasis indirectly through lipid metabolism.
- **Cell Cycle Regulation and Differentiation:** Impact on cellular proliferation and differentiation in various tissues.

### Conclusion

The PPARA gene is critical for regulating multiple metabolic processes and provides significant insights into how lipid metabolism interfaces with aging and age-related diseases. Its interactions with various drugs highlight its therapeutic potential, particularly in metabolic syndromes and related pathologies. Understanding PPARA's role in these processes continues to be a focus for both basic and clinical research.