Improved Expression of Sirt1 on Thymic Epithelial Cells of SAMP10 after Intrabone Marrow–Bone Marrow Transplantation

Abstract

Aging is accompanied by various forms of immune dysfunction, leading to an increase in frequency of infections and the development of malignant tumors in mice and humans. Sirt1 has been implicated in processes as varied as metabolism, differentiation, cancer, and the stress response and aging. Senescence-accelerated mice prone 10 (SAMP10) show not only spontaneously occurring brain atrophy, with deficits in learning and memory, but also emotional disorders. We attempted in this study to clarify the deficits and found that the percentage of CD4/TNF-α T-cells in the spleen of 24-week-old (but not 6-week-old) SAMP10 to be significantly reduced. The thymus was significantly lighter, and the percentage of CD4 + CD8 + cells was significantly lower in the 24-week-old SAMP10 than 6-week-old SAMP10. Microarray analyses indicated that genes related to transcription coactivator activity, growth factor activity, hormone activity, cytokine activity, receptor activity, and regulation of the immune system were downregulated in the thymus of 24-week-old SAMP10. Real-time PCR analysis showed that the expression of KGF, Aire, and Sirt1 was decreased on the thymic epithelial cells (TECs) of 24-week-old SAMP10. However, these parameters improved after the mice were treated with intrabone marrow–bone marrow transplantation. This is the first report of age-related changes in immune system dysfunction in 24-week-old SAMP10 and the first to show that dysfunction on the TECs of 24-week-old SAMP10 was modulated by allogeneic bone marrow cells.