Reversing Somatic Mosaicism in Aged Tissue

In this study, we focused on p53 mutations because these are the most enriched during malignant transformation. p53 is mutated in 5%-10% of normal EE but in almost all esophageal squamous cell carcinomas (ESCCs). This argues that ESCC emerges from the p53 mutant cell population in normal epithelium and that mutation of p53 is required for cancer development. We speculated that altering the selective pressure on mutant cell populations may cause them to expand or contract. We tested this hypothesis by examining the effect of oxidative stress from low-dose ionizing radiation (LDIR) on wild-type and p53 mutant cells in the mouse esophagus. We found that LDIR drives wild-type cells to stop proliferating and differentiate. p53 mutant cells are insensitive to LDIR and outcompete wild-type cells following exposure. Remarkably, combining antioxidant treatment and LDIR reverses this effect, promoting wild-type cell proliferation and p53 mutant differentiation, reducing the p53 mutant population. Thus, p53-mutant cells can be depleted from the normal esophagus by redox manipulation, showing that external interventions may be used to alter the mutational landscape of an aging tissue. Link: https://doi.org/10.1016/j.stem.2019.06.011
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs