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

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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.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH) grants AG031736, AG0119899, and AG051869 (to A.B.) and AG048264 and AG050531 (to L.Y.S.). This work is solely the view of the authors and does not reflect those of the NIH.

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Authors and Affiliations

  1. Department of Internal Medicine, Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62794-9628, USA

    Yimin Fang, Samuel McFadden, Justin Darcy, Joshua A. Huber & Andrzej Bartke

  2. Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA

    Justin Darcy

  3. Department of Neurosignaling, Pennington Biomedical Research Center, Baton Rouge, LA, USA

    Cristal M. Hill

  4. Center for Clinical Research, Southern Illinois University School of Medicine, Springfield, IL, USA

    Steve Verhulst

  5. Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA

    John J. Kopchick

  6. Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA

    Richard A. Miller

  7. Department of Biology, University of Alabama at Birmingham, Birmingham, AL, USA

    Liou Y. Sun

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  1. Yimin Fang
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  2. Samuel McFadden
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  3. Justin Darcy
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  4. Cristal M. Hill
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  5. Joshua A. Huber
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  6. Steve Verhulst
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  7. John J. Kopchick
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  8. Richard A. Miller
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  9. Liou Y. Sun
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  10. Andrzej Bartke
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Corresponding author

Correspondence to Yimin Fang.

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All animal protocols were approved by the Southern Illinois University School of Medicine Animal Care and Use Committee.

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Fang, Y., McFadden, S., Darcy, J. et al. Differential effects of early-life nutrient restriction in long-lived GHR-KO and normal mice. GeroScience 39, 347–356 (2017). https://doi.org/10.1007/s11357-017-9978-6

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  • DOI: https://doi.org/10.1007/s11357-017-9978-6

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