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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on March 20, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp024
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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.

Insulin Sensitivity as a Key Mediator of Growth Hormone Actions on Longevity

Michal M. Masternak1, Jacob A. Panici1, Michael S. Bonkowski1, Larry F. Hughes2 and Andrzej Bartke1,3

1 Department of Internal Medicine
2 Department of Surgery
3 Department of Physiology, Southern Illinois University School of Medicine, Springfield

Address correspondence to Michal M. Masternak, PhD, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794. Email: mmasternak{at}siumed.edu


  Abstract

Reduced insulin sensitivity and glucose intolerance have been long suspected of having important involvement in aging. Here we report that in studies of calorie restriction (CR) effects in mutant (Prop1df and growth hormone receptor knockout [GHRKO]) and normal mice, insulin sensitivity was strongly associated with longevity. Of particular interest was enhancement of the already increased insulin sensitivity in CR df/df mice in which longevity was also further extended and the lack of changes in insulin sensitivity in calorically restricted GHRKO mice in which there was no further increase in average life span. We suggest that enhanced insulin sensitivity, in conjunction with reduced insulin levels, may represent an important (although almost certainly not exclusive) mechanism of increased longevity in hypopituitary, growth hormone (GH)-resistant, and calorie-restricted animals. We also report that the effects of GH treatment on insulin sensitivity may be limited to the period of GH administration.

Keywords Insulin; Longevity; GHRKO; Ames dwarf

Received: March 24, 2008; Accepted: August 5, 2008

Decision Editor: Huber R. Warner, PhD


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