Vilon Modulates Gene Expression and Extends Lifespan in Senescence-Accelerated Mice
Khavinson V.K., Kuznik B.I., Tarnovskaya S.I.
St. Petersburg Institute of Bioregulation and Gerontology
Biogerontology 8(4): 387-398
Abstract
Short peptides are hypothesized to act as gene regulators by binding to specific DNA sequences. This study investigated Vilon (Lys-Glu), a synthetic dipeptide derived from thymus. Senescence-accelerated mice (SAMP1 strain, known for premature aging) received Vilon (100 μg/kg, subcutaneous, 3x/week) from 2 months of age. Vilon treatment extended median lifespan by 38.4% (14.2±1.8 months vs. control 10.3±1.4, p<0.0001) and maximum lifespan from 16.7 to 21.3 months (+27.5%). Chromatin immunoprecipitation (ChIP) assays demonstrated Vilon binds to promoter regions of IL-2 and interferon-γ genes, enhancing transcription. Gene expression profiling revealed upregulation of 47 immunity-related genes and downregulation of 23 pro-inflammatory genes. Flow cytometry confirmed increased CD4+ and CD8+ T-cell populations. Remarkably, at molecular weight of only 274 Da, Vilon represents one of the smallest known geroprotective molecules.
Study Population
SAMP1 mice (senescence-accelerated prone strain), males, treatment started at 2 months of age
The Big Question
Can a molecule as simple as a dipeptide (just 2 amino acids) really affect aging? This study sought to answer that question.
Experimental Approach
Mice genetically prone to rapid aging (SAMP1 strain) were treated with Vilon throughout their lives.
Remarkable Findings
Lifespan Extension
Vilon extended median lifespan by an astounding 38% - one of the largest extensions ever reported for a peptide intervention.
Molecular Mechanism Revealed
Using cutting-edge ChIP (chromatin immunoprecipitation) technology, researchers proved Vilon physically binds to DNA:
- Specifically targets the promoter region of immune system genes
- Activates IL-2 (key T-cell growth factor)
- Activates interferon-γ (antiviral immunity)
Gene Expression Remodeling
Vilon upregulated 47 beneficial immunity genes while silencing 23 inflammatory genes, essentially "reprogramming" the aging immune system.
Paradigm Shift
This study demonstrates that extremely short peptides can function as gene switches, challenging the dogma that only large transcription factors regulate gene expression.
Statistical Results
Median lifespan: Vilon 14.2±1.8 months vs. control 10.3±1.4 (+38.4%, p<0.0001). Maximum lifespan: 21.3 vs. 16.7 months (+27.5%). IL-2 mRNA expression: 3.7-fold increase (p<0.001). CD4+ T-cells: Vilon 42.3±4.2% vs. control 28.7±3.8% (p<0.001). ChIP enrichment at IL-2 promoter: 4.2-fold (p<0.01).
Study Limitations
- •Mouse model may not perfectly translate to humans
- •Specific strain (SAMP1) has accelerated aging - not normal aging
- •Mechanism limited to IL-2/IFN-γ genes - other targets unknown
- •No cancer incidence data reported
Key Findings
- ✓Dramatic lifespan extension (38%)
- ✓Direct DNA binding demonstrated
- ✓Gene expression remodeling
- ✓Restored youthful immune profiles
Mechanism of Action
Direct binding to promoter regions of immunity genes (IL-2, IFN-γ), acting as a micro-transcription factor.