Does Aging Induce Cellular Mosaicism?

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The major findings made by this study project are summarized below.1. During aging, we found increases in the gene expression of a retrovirus, mouse mammary tumor virus (MMTV). This retrovirus plays a crucial role in mammary tumorigenesis. Insertional mutations of MMTV were often found in DNA from tumors, indicating that retroviruses can bring about cellular mosaicism during aging.2. It is recently reported that the Lyonized X chromosome can be reactivated during aging. If so, reactivation of the inactivated X chromosome is assumed to be able to induce cellular mosaicism as well as retroviruses. We examined this possibility in mice having Searle's translocation. The results, however, indicated the Lyonization is stably maintained both during aging and in carcinogenesis process. We, thus, concluded that reactivation of X chromosome cannot bring about cellular mosaicism.3. We also demonstrated that during the cellular death and degeneration processes, some clones proliferate more preferentially than others.4. Finally we investigated a role of the regulatory center on the X chromosome in regulating gene expression on the autosomal chromosomes. Our results indicated the regulation by the X chromosome tightly maintained even after the cellular death and degeneration process.In conclusion, the cellular mosaicism was found to occur during aging through insertional mutations by retrovirus.