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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 19, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp017
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Reduced Incidence and Delayed Occurrence of Fatal Neoplastic Diseases in Growth Hormone Receptor/Binding Protein Knockout Mice

Yuji Ikeno1,2,3, Gene B. Hubbard4, Shuko Lee3, Lisa A. Cortez1, Christie M. Lew1, Celeste R. Webb1, Darlene E. Berryman5, Edward O. List5, John J. Kopchick5,6 and Andrzej Bartke7

1 The Barshop Institute for Longevity and Aging Studies
2 Department of Pathology, The University of Texas Health Science Center at San Antonio
3 Research Service, Audie Murphy VA Hospital (STVHCS), San Antonio, Texas
4 Department of Comparative Medicine, Southwest Foundation for Biomedical Research, San Antonio, Texas
5 Edison Biotechnology Institute, Ohio University, Athens
6 College of Osteopathic Medicine, Ohio University, Athens
7 Department of Internal Medicine and Physiology, Southern Illinois University School of Medicine, Springfield

Address correspondence to Yuji Ikeno, MD, PhD, Barshop Institute for Longevity and Aging Studies and Department of Pathology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207. Email: ikeno{at}uthscsa.edu


  Abstract

Although studies of Ames and Snell dwarf mice have suggested possible important roles of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in aging and age-related diseases, the results cannot rule out the possibility of other hormonal changes playing an important role in the life extension exhibited by these dwarf mice. Therefore, growth hormone receptor/binding protein (GHR/BP) knockout (KO) mice would be valuable animals to directly assess the roles of somatotropic axis in aging and age-related diseases because the primary hormonal change is due to GH/IGF-1 deficiency. Our pathological findings showed GHR/BP KO mice to have a lower incidence and delayed occurrence of fatal neoplastic lesions compared with their wild-type littermates. These changes of fatal neoplasms are similar to the effects observed with calorie restriction and therefore could possibly be a major contributing factor to the extended life span observed in the GHR/BP KO mice.

Keywords Growth hormone receptor/binding protein; Knockout mouse; Neoplastic disease; Aging

Received: September 29, 2008; Accepted: January 2, 2009

Decision Editor: Huber R. Warner, PhD


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