title: 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.
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.
authors: Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL 62702-4910, USA. adges7@wp.pl
authors: Adam
authors: A
authors: Gesing
authors: Michal M
authors: MM
authors: Masternak
authors: Feiya
authors: F
authors: Wang
authors: Malgorzata
authors: M
authors: Karbownik-Lewinska
authors: Andrzej
authors: A
authors: Bartke
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D031204:Caloric Restriction; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000601:surgery*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D011986:Receptors, Somatotropin; D012313:RNA