GeroScience

, Volume 39, Issue 3, pp 347–356 | Cite as

Differential effects of early-life nutrient restriction in long-lived GHR-KO and normal mice

  • Yimin Fang
  • Samuel McFadden
  • Justin Darcy
  • Cristal M. Hill
  • Joshua A. Huber
  • Steve Verhulst
  • John J. Kopchick
  • Richard A. Miller
  • Liou Y. Sun
  • Andrzej Bartke
Original Article
  • 94 Downloads

Abstract

There is increasing evidence that growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling (collectively referred to as somatotropic signaling) during development has a profound influence on aging and longevity. Moreover, the absence of GH action was shown to modify responses of adult mice to calorie restriction (CR) and other antiaging interventions. It was therefore of interest to determine whether GH resistance in GH receptor knockout (GHR-KO) mice would modify the effects of mild pre-weaning CR imposed by increasing the number of pups in a litter (the so-called litter crowding). In addition to the expected impact on body weight, litter crowding affected glucose homeostasis, hepatic expression of IGF-1 and genes related to lipid metabolism, and expression of inflammatory markers in white adipose tissue, with some of these effects persisting until the age of 2 years. Litter crowding failed to further extend the remarkable longevity of GHR-KO mice and, instead, reduced late life survival of GHR-KO females, an effect opposite to the changes detected in normal animals. We conclude that the absence of GH actions alters the responses to pre-weaning CR and prevents this intervention from extending longevity.

Keywords

GHR-KO Growth hormone Litter crowding Aging 

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Copyright information

© American Aging Association 2017

Authors and Affiliations

  • Yimin Fang
    • 1
  • Samuel McFadden
    • 1
  • Justin Darcy
    • 1
    • 2
  • Cristal M. Hill
    • 3
  • Joshua A. Huber
    • 1
  • Steve Verhulst
    • 4
  • John J. Kopchick
    • 5
  • Richard A. Miller
    • 6
  • Liou Y. Sun
    • 7
  • Andrzej Bartke
    • 1
  1. 1.Department of Internal MedicineSouthern Illinois University School of MedicineSpringfieldUSA
  2. 2.Department of Medical Microbiology, Immunology and Cell BiologySouthern Illinois University School of MedicineSpringfieldUSA
  3. 3.Department of NeurosignalingPennington Biomedical Research CenterBaton RougeUSA
  4. 4.Center for Clinical ResearchSouthern Illinois University School of MedicineSpringfieldUSA
  5. 5.Heritage College of Osteopathic MedicineOhio UniversityAthensUSA
  6. 6.Department of Pathology and Geriatrics CenterUniversity of MichiganAnn ArborUSA
  7. 7.Department of BiologyUniversity of Alabama at BirminghamBirminghamUSA

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