title: Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice.
abstract: We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity. DOI:http://dx.doi.org/10.7554/eLife.01098.001.
authors.affiliation: Department of Internal Medicine , Southern Illinois University School of Medicine , Springfield , United States.
authors.forename: Liou Y
authors.initials: LY
authors.lastname: Sun
authors.forename: Adam
authors.initials: A
authors.lastname: Spong
authors.forename: William R
authors.initials: WR
authors.lastname: Swindell
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fang
authors.forename: Cristal
authors.initials: C
authors.lastname: Hill
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Huber
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Boehm
authors.forename: Reyhan
authors.initials: R
authors.lastname: Westbrook
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D020869:Gene Expression Profiling; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D007018:Hypopituitarism / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D008136:Longevity; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010641:Phenotype; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D015262:Xenobiotics; D013007:Growth Hormone-Releasing Hormone
keywords: Mouse; aging; caloric restriction; growth hormone; mice