Expression of p16INK4a prevents cancer and promotes aging in lymphocytes

Abstract

Previous authors have suggested that tumor suppressor expression promotes aging while preventing cancer, but direct experimental support for this canceraging hypothesis has been elusive. Here, by using somatic, tissue-specific inactivation of the p16INK4a tumor suppressor in murine T- or B-lymphoid progenitors, we report that ablation of p16INK4a can either rescue aging or promote cancer in a lineage-specific manner. Deletion of p16INK4a in the T lineage ameliorated several aging phenotypes, including thymic involution, decreased production of naive T cells, reduction in homeostatic T-cell proliferation, and attenuation of antigen-specific immune responses. Increased T-cell neoplasia was not observed with somatic p16 INK4a inactivation in T cells. In contrast, B lineage-specific ablation of p16INK4a was associated with a markedly increased incidence of systemic, high-grade B-cell neoplasms, which limited studies of the effects of somatic p16INK4a ablation on B-cell aging. Together, these data show that expression of p16INK4a can promote aging and prevent cancer in related lymphoid progeny of a common stem cell. © 2011 by The American Society of Hematology.