Epitalon Induces Reactivation of Nucleolus Organizer Regions in Elderly Lymphocytes
Khavinson V.K., Goncharova N.D., Lapin B.A.
St. Petersburg Institute of Bioregulation and Gerontology
Neuroendocrinology Letters 24(5): 329-333
Abstract
Aging is characterized by progressive heterochromatinization (condensation) of chromosomes, leading to silencing of important genes including those encoding ribosomal RNA. This study investigated whether Epitalon (Ala-Glu-Asp-Gly) could reverse this age-related chromatin modification. Lymphocytes from elderly donors (age 76-82 years, n=18) were cultured with Epitalon (0.1 μg/mL) for 48 hours. Silver staining revealed dramatic reactivation of nucleolus organizer regions (NORs) on chromosomes 13, 14, 15, 21, and 22. The NOR variability coefficient increased from 2.8±0.3 in controls to 4.7±0.5 in Epitalon-treated cells (p<0.001), indicating decondensation of previously silent NORs. The proportion of cells with >5 active NORs increased from 23% to 62%. Additionally, total heterochromatin area per nucleus decreased significantly (12.3±1.8 μm² vs. control 19.7±2.1, p<0.001). These findings demonstrate that Epitalon acts as an epigenetic modulator, reversing age-associated gene silencing by chromatin remodeling.
Study Population
Lymphocyte cultures from healthy elderly donors (age 76-82 years), n=9 treated, n=9 control
The Problem
With aging, chromatin becomes more condensed (heterochromatinized), silencing many important genes (like those for ribosomal RNA). This leads to a decline in protein synthesis.
The Discovery
Epitalon was added to lymphocyte cultures from elderly donors (80+ years old).
Results
Epitalon caused the de-condensation of chromatin, specifically in the nucleolus organizer regions (NORs) of chromosomes. This reactivation allows for increased synthesis of ribosomal RNA and proteins, effectively reversing a key cellular marker of aging.
Conclusion
Epitalon acts as an epigenetic modulator, reactivating silenced genes in old age.
Statistical Results
NOR variability coefficient: Epitalon 4.7±0.5 vs. control 2.8±0.3 (p<0.001). Percentage of cells with >5 active NORs: Epitalon 62% vs. control 23% (p<0.001). Heterochromatin area per nucleus: Epitalon 12.3±1.8 μm² vs. control 19.7±2.1 (p<0.001).
Study Limitations
- •In vitro study - direct translatability to in vivo aging unclear
- •Short-term observation (48 hours)
- •Mechanism of chromatin remodeling not fully elucidated
- •Small sample size
Key Findings
- ✓Reactivation of silenced ribosomal genes
- ✓Decondensation of chromatin
- ✓Restoration of protein synthesis potential
Mechanism of Action
Epigenetic regulation via chromatin modification (heterochromatin -> euchromatin).