The GH/IGF-1 axis in ageing and longevity

Abstract

Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the 'somatopause', has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans.

Key Points

  • Growth hormone (GH) is a potent metabolic hormone that has been touted as a 'fountain of youth'

  • Recombinant human (rh) GH and insulin-like growth factor 1 (IGF-1) are approved therapeutics for patients with GH deficiency or primary IGF-1 deficiency, respectively; however, these drugs have been misused

  • Currently available data do not suggest that rhGH treatment should be used to promote longevity

  • Lack of GH action in mouse models is associated with extended longevity, but the mechanism underlying the increased lifespan has yet to be established

  • Given the effects of reduced GH/IGF-1 signalling on lifespan in rodents, decreased GH action might be beneficial for humans, but clinical trials are needed to assess long-term outcome of GH/IGF-1 inhibition

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Figure 1: Factors of the GH/IGF-1 axis known to influence ageing.
Figure 2: Mouse strains with altered GH signalling.

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Acknowledgements

The authors thank J. Sattler at Ohio University Heritage College for Osteopathic Medicine, Athens, OH, USA for taking the mouse photograph. J. J. Kopchick is supported by the State of Ohio's Eminent Scholar Program, which includes a gift from Milton and Lawrence Goll, by AMVETS, and by NIH (P01AG031736).

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R. K. Junnila and J. W. Murrey researched the data for the article. R. K. Junnila and J. J. Kopchick contributed equally to writing the article. All authors provided a substantial contribution to discussions of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to John J. Kopchick.

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J. J. Kopchick declares that he is an inventor of US patent 5350836 entitled 'Growth hormone antagonists'. The other authors declare no competing interests.

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Junnila, R., List, E., Berryman, D. et al. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 9, 366–376 (2013). https://doi.org/10.1038/nrendo.2013.67

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