Insulin Growth Factor-I Inhibits Apoptosis in Hematopoietic: Progenitor Cells Implications in Thymic Aging

• Published in: Annals of the New York Academy of Sciences 1998-05, Vol.840 (1), p.518-524
• Main Authors: KELLEY, KEITH W., MEIER, WILLIAM A., MINSHALL, CHRISTIAN, SCHACHER, DANIEL H., LIU, QIANG, VANHOY, ROGER, BURGESS, WILLIAM, DANTZER, ROBERT
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Apoptosis - drug effects; Enzyme Activation - physiology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Humans; Insulin-Like Growth Factor I - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Thymus Gland - physiology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.1998.tb09590.x

A decline in plasma concentrations of both growth hormone and IGF-I occurs during aging of humans and rodents, and this is accompanied by involution of the thymus gland. Exogenous growth hormone induces the synthesis of IGF-I, which acts on bone marrow-derived hematopoietic progenitors of the myeloid and lymphoid lineages to promote their replication and survival. The increase in survival of these cells is caused by the ability of IGF-I to inhibit their apoptotic death. In contrast to the multipotential colony-stimulating-factor IL-3, inhibition of apoptosis by IGF-I requires the activation of the critical intracellular effector PI 3-kinase. These data establish that hematopoietic progenitors can use more than one intracellular signaling pathway in order to maintain their survival. The data also extend the original hypothesis that IGF-I shares with the colony-stimulating factors the properties of promoting DNA synthesis and inhibiting programmed cell death. Collectively, these data establish that hematopoietic progenitor cells are important targets for IGF-I, and this is likely to be important in understanding thymic aging.