GH receptor knockout (GHRKO) mice were produced by a targeted disruption of the GH receptor (Ghr) gene. These long-lived mice, which are GH resistant, are characterized by a greatly reduced plasma levels of IGF1 and insulin and have enhanced insulin sensitivity (these effects resemble the characteristics of animals subjected to caloric restriction (CR), which is well known experimental model to delay aging and increase lifespan).
Apoptosis, or programmed cell death, is a normal component of the development and health of multicellular organisms and is a process in which cells play an active role in their own death (which is why apoptosis is often referred to as cell suicide).
The aim of the study was to examine the expression of genes related to apoptosis (using real-time PCR) in the homogenates of skeletal muscles and hearts collected from female GHRKO mice subjected to CR (40%; 6 months), starting at 2 months of age.
Results: Expression of the examined apoptotic genes (caspase 3, caspase 9, bax, Smac/DIABLO) is decreased in skeletal muscles of GHRKO mice as compared to normal controls (P<0.03, P<0.007, P<0.04, P<0.04, respectively); no statistical differences were observed for the genes in question in hearts of GHRKO mice (in comparison to normals). CR increased caspase 3 expression in homogenates of hearts in normal and GHRKO mice.
Conclusion: Whereas expression of apoptosis-related genes is decreased in skeletal muscles, but not in hearts, of GHRKO mice, it is not clearly affected by caloric restriction in either tissue (supported by NIA).
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology