Deletion of growth hormone receptor gene but not visceral fat removal decreases expression of apoptosis-related genes in the kidney-potential mechanism of lifespan extension

Age (Dordr). 2012 Apr;34(2):295-304. doi: 10.1007/s11357-011-9232-6. Epub 2011 Mar 23.

Abstract

Mice homozygous for the targeted disruption of the growth hormone (GH) receptor (Ghr) gene (GH receptor knockout; GHRKO; KO) are hypoinsulinemic, highly insulin sensitive, normoglycemic, and long-lived. Visceral fat removal (VFR) is a surgical intervention which improves insulin signaling in normal (N) mice and rats and extends longevity in rats. We have previously demonstrated decreased expression level of certain pro-apoptotic genes in skeletal muscles and suggested that this may contribute to the regulation of longevity in GHRKO mice. Alterations in apoptosis-related genes expression in the kidneys also may potentially lead to lifespan extension. In this context, we decided to examine the renal expression of the following genes: caspase-3, caspase-9, caspase-8, bax, bad, bcl-2, Smac/DIABLO, Apaf-1, p53, and cytochrome c1 (cyc1) in male GHRKO and N mice subjected to VFR or sham surgery, at approximately 6 months of age. The kidneys were collected 2 months after VFR. As a result, caspase-3, caspase-9, and bax expressions were decreased in KO mice as compared to N animals. Expressions of Smac/DIABLO, caspase-8, bcl-2, bad, and p53 did not differ between KOs and N mice. VFR did not change the expression of the examined genes in KO or N mice. In conclusion, endocrine abnormalities in GHRKO mice result in decreased expression of pro-apoptotic genes and VFR did not alter the examined genes expression in N and KO mice. These data are consistent with a model in which alterations of GH signaling and/or insulin sensitivity lead to increased lifespan mediated by decreased renal expression of pro-apoptotic genes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Apoptosis / genetics
  • Apoptotic Protease-Activating Factor 1 / biosynthesis
  • Apoptotic Protease-Activating Factor 1 / genetics*
  • Caloric Restriction
  • Female
  • Gene Deletion
  • Gene Expression*
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / surgery*
  • Kidney / cytology
  • Kidney / metabolism
  • Longevity / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • RNA / genetics*
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Receptors, Somatotropin / biosynthesis
  • Receptors, Somatotropin / genetics*
  • Signal Transduction

Substances

  • Apoptotic Protease-Activating Factor 1
  • Receptors, Somatotropin
  • RNA