Insulin-like Growth Factor I (IGF-1) is a hormone secreted by the liver as a result of the stimulation of Growth Hormone (GH). If Growth Hormone receptors are blocked, less IGF is produced. It is possible that this lower production of IGF-1 helps minimize the development of insulin resistance, as would a calorie reduced diet.

Mice with the GH receptor gene knocked out are called GHRKO mice. They tend to be longer lived than normal mice. In the study described in the article, a group of GHRKO mice were compared with normal mice. They were either fed normally or on a 30% Calorie Restriction diet starting from 2 months of age.

"In the normal, non-GHRKO mice, Calorie Restriction produced the expected increases in overall, average, median, and maximal life span.

In the mice with no GH receptors (GHRKO), Calorie Restriction failed to increase overall, median, or average life span in GHRKO mice and increased maximal life span only in females"

Calorie restriction also increases insulin sensitivity in the normal mice, but does not do so in the GHRKO mice who already have a high degree of insulin sensitivity.

The authors conclude that this tends to support the idea that enhanced sensitivity to insulin plays a prominent role in the actions of Calorie Restriction and Growth Hormone resistance on longevity.