Insulin Growth Factor‐I Inhibits Apoptosis in Hematopoietic: Progenitor Cells Implications in Thymic Aging^a

Abstract

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.

Persistent Infection of Thymic Epithelial Cells with Coxsackievirus B4 Results in Decreased Expression of Type 2 Insulin-Like Growth Factor

“…IGF-1 acts as a positive thymic regulator by stimulating thymus growth and thymopoiesis (12,33). Indeed, it has been observed that age-related declines in thymic function paralleled declines in plasma concentrations of IGF-1 (35). In murine fetal thymic organ cultures, inhibition of IGF-1 by antibody blockade resulted in significant changes in total thymocyte numbers and subset composition (33).…”

How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

“…IGF-1 has been shown to rescue the aging-related or inactivity-induced loss of muscle mass through the activation of satellite cells (Machida and Booth, 2004). Other stem and progenitor cell types where IGF-1 has been shown to be important for proliferation and differentiation include cardiac muscle stem cells, neuronal stem cells, hematopoietic stem cells, mesenchymal stem cells, and adipocytes (Kelley et al, 1998;Merchav, 1998;Schulze and Spate, 2005;Spagnoli et al, 2005;Wabitsch et al, 1995).…”

Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion

“…21 In the thymus, IGF-1 has been implicated as a positive thymic regulator based on early observations that age-related declines in thymic function paralleled declines in plasma concentrations of IGF-1. 22 IGF-1 receptor (IGF-1R) is expressed on thymocytes and peripheral T cells. 23,24 In murine fetal thymic organ cultures, inhibition of IGF-1 by antibody blockade resulted in significant changes in total thymocyte numbers and subset composition.…”