Insulin growth factor-I inhibits apoptosis in hematopoietic progenitor cells. Implications in thymic aging.
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.
Kelley
K W
KW
Department of Animal Sciences, University of Illinois, Urbana 61801, USA. kwkelley@uiuc.edu
Meier
W A
WA
Minshall
C
C
Schacher
D H
DH
Liu
Q
Q
VanHoy
R
R
Burgess
W
W
Dantzer
R
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004789:Enzyme Activation / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D013950:Thymus Gland / Q000502:physiology*
D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases