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The slow-aging growth hormone receptor/binding protein gene-disrupted (GHR-KO) mouse is protected from aging-resultant neuromusculoskeletal frailty

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Abstract

Neuromusculoskeletal (physical) frailty is an aging-attributable biomedical issue of extremely high import, from both public health and individual perspectives. Yet, it is rarely studied in nonhuman research subjects and very rarely studied in animals with extended longevity. In an effort to address this relatively neglected area, we have conducted a longitudinal investigation of the neuromusculoskeletal healthspan in mice with two senescence-slowing interventions: growth hormone (GH) resistance, produced by GH receptor “knockout” (GHR-KO), and caloric restriction (CR). We report marked improvements in the retention of strength, balance, and motor coordination by the longevity-conferring GHR/BP gene disruption, CR regimen, or a combination of the two. Specifically, GHR-KO mice exhibit superior grip strength, balance, and motor coordination at middle age, and CR mice display superior grip strength at middle age. The advantageous effects established by middle-age are more pronounced in old-age, and these robust alterations are, generally, not gender-specific. Thus, we show that genetic and/or dietary interventions that engender longevity are also beneficial for the retention of neuromusculoskeletal health and functionality. The translational knowledge to be gained from subsequent molecular or histological investigations of these models of preserved functionality and decelerated senescence is potentially relevant to the efforts to reduce the specter of fear, falls, fracture, and frailty in the elderly.

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Acknowledgments

We thank Lisa Cox for the technical assistance, Steve Sandstrom for the copyediting, and Ravneet Boparai, Ph.D., for the photographic assistance. This work was supported by the National Institute on Aging Grants AG19899, U19 AG023122, and 3R01AG019899-07S1, as well as a Senior Scholar Award in Aging from The Ellison Medical Foundation, and The Glenn Foundation for Medical Research; this work was vitally supported by a grant from the Center for Alzheimer’s Disease and Related Disorders at The Southern Illinois University, and the authors would especially like to thank Thomas A. Ala, M.D., and Robert G. Struble, Ph.D.

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Authors and Affiliations

  1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, 62794, USA

    Oge Arum, Dustin J. Rickman & Andrzej Bartke

  2. Edison Biotechnology Institute and Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA

    John J. Kopchick

  3. 631 N. 6th St., 2B, Springfield, IL, 62702, USA

    Oge Arum

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  1. Oge Arum
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  2. Dustin J. Rickman
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Correspondence to Oge Arum.

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Arum, O., Rickman, D.J., Kopchick, J.J. et al. The slow-aging growth hormone receptor/binding protein gene-disrupted (GHR-KO) mouse is protected from aging-resultant neuromusculoskeletal frailty. AGE 36, 117–127 (2014). https://doi.org/10.1007/s11357-013-9551-x

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