### MTHFD1L Gene Overview

**Gene Symbol**: MTHFD1L  
**Location**: Chromosome 2q37.1  
**Function**: The MTHFD1L gene encodes a mitochondrial enzyme involved in the synthesis of tetrahydrofolate (THF). It plays a crucial role in one-carbon metabolism, essential for the de novo synthesis of purines and thymidylate as well as in the regeneration of methionine from homocysteine.

### 1. Associated Genes

MTHFD1L is primarily associated with several key genes involved in folate metabolism and related pathways:

- **MTHFD2**: An enzyme that performs similar functions in one-carbon metabolism and is known to work complementarily with MTHFD1L.
- **MTHFR** (Methylenetetrahydrofolate reductase): While not directly interacting, it’s involved in the same metabolic pathways and is crucial in THF regulation.
- **SHMT1 and SHMT2** (Serine hydroxymethyltransferase): These genes are also involved in one-carbon metabolism.
- **GART** (Phosphoribosylglycinamide formyltransferase): Related to purine metabolism.
- **MAT2A** (Methionine adenosyltransferase 2A): Involved in methionine metabolism.

### 2. Aging and Age-Related Disease Associations

Research suggests that MTHFD1L may play a role in age-related diseases, particularly those associated with folate deficiency and metabolism:

- **Cardiovascular Diseases**: Dysfunction in one-carbon metabolism can lead to elevated homocysteine levels, which are associated with cardiovascular risks.
- **Neurodegenerative Disorders**: Folate metabolism is linked to neural health; alterations in MTHFD1L function may impact conditions such as Alzheimer's disease due to the critical role of THF in neuronal function and repair.
- **Cancer**: Changes in the folate pathway are often seen in various cancers. The precise regulation of MTHFD1L may influence tumorigenesis through its impact on nucleotide synthesis and cellular proliferation.

### 3. Drug or Drug Classes Interactions

While there aren't known specific drugs that target MTHFD1L directly, several drug classes may influence its activity indirectly:

- **Folate Supplements**: These can impact THF levels and, subsequently, the activity of MTHFD1L.
- **Methotrexate**: A chemotherapy agent that inhibits dihydrofolate reductase (DHFR), impacting folate metabolism and may indirectly affect MTHFD1L function.
- **Choline/Betaines**: Nutrients that can influence one-carbon metabolism and thus modulate the effects of MTHFD1L through altered levels of THF.

### 4. Pathways and Biological Processes

MTHFD1L is involved in several important biological processes and metabolic pathways:

- **One-carbon Metabolism**: Central to nucleotide biosynthesis and amino acid metabolism.
- **Purine and Thymidylate Biosynthesis**: Essential for DNA synthesis and repair.
- **Mitochondrial Metabolism**: Involvement in mitochondrial processes highlights its importance in cellular energy metabolism and metabolic regulation.
- **Methionine Cycle**: Plays an essential role in the regeneration of methionine from homocysteine, linking to S-adenosylmethionine (SAM) production, a key methyl donor in numerous biological processes.
- **Folate Biosynthesis**: Contributes to overall folate metabolism, affecting cellular functions at multiple levels.

### Summary

The MTHFD1L gene plays a crucial role in mitochondrial folate metabolism and is associated with other genes involved in one-carbon metabolism. It potentially impacts various diseases related to aging, particularly through its effects on cardiovascular health and neurodegenerative conditions. While no specific drugs target MTHFD1L, several lifestyle and pharmacological factors may influence its function. Understanding the pathways involved can provide insights into its broader biological significance.