Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

Liou Y. Sun, Adam Spong, William R. Swindell, Yimin Fang, Cristal Hill, Joshua A. Huber, Jacob D. Boehm, Reyhan Westbrook, Roberto Salvatori, Andrzej Bartke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere01098
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Oct 29 2013

Fingerprint

Growth Hormone-Releasing Hormone
Caloric Restriction
Insulin
Detoxification
Adiponectin
Xenobiotics
Knockout Mice
Growth Hormone
Insulin Resistance
Homeostasis
Down-Regulation
Genes
Aging of materials
Inflammation
Gene Expression
Glucose
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Sun, L. Y., Spong, A., Swindell, W. R., Fang, Y., Hill, C., Huber, J. A., ... Bartke, A. (2013). Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. eLife, 2013(2), [e01098]. https://doi.org/10.7554/eLife.01098.001

Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. / Sun, Liou Y.; Spong, Adam; Swindell, William R.; Fang, Yimin; Hill, Cristal; Huber, Joshua A.; Boehm, Jacob D.; Westbrook, Reyhan; Salvatori, Roberto; Bartke, Andrzej.

In: eLife, Vol. 2013, No. 2, e01098, 29.10.2013.

Research output: Contribution to journalArticle

Sun, Liou Y. ; Spong, Adam ; Swindell, William R. ; Fang, Yimin ; Hill, Cristal ; Huber, Joshua A. ; Boehm, Jacob D. ; Westbrook, Reyhan ; Salvatori, Roberto ; Bartke, Andrzej. / Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. In: eLife. 2013 ; Vol. 2013, No. 2.
@article{4e6cf4c108814f159931d8c9a0913754,
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.",
author = "Sun, {Liou Y.} and Adam Spong and Swindell, {William R.} and Yimin Fang and Cristal Hill and Huber, {Joshua A.} and Boehm, {Jacob D.} and Reyhan Westbrook and Roberto Salvatori and Andrzej Bartke",
year = "2013",
month = "10",
day = "29",
doi = "10.7554/eLife.01098.001",
language = "English (US)",
volume = "2013",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "2",

}

TY - JOUR

T1 - Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice

AU - Sun, Liou Y.

AU - Spong, Adam

AU - Swindell, William R.

AU - Fang, Yimin

AU - Hill, Cristal

AU - Huber, Joshua A.

AU - Boehm, Jacob D.

AU - Westbrook, Reyhan

AU - Salvatori, Roberto

AU - Bartke, Andrzej

PY - 2013/10/29

Y1 - 2013/10/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84887366856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887366856&partnerID=8YFLogxK

U2 - 10.7554/eLife.01098.001

DO - 10.7554/eLife.01098.001

M3 - Article

VL - 2013

JO - eLife

JF - eLife

SN - 2050-084X

IS - 2

M1 - e01098

ER -