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Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age

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An Erratum to this article was published on 09 August 2014

Abstract

Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals. Furthermore, we institute a dietary restriction paradigm that also decelerates aging, an intermittent fasting (IF) feeding schedule, as either a short-term or a sustained intervention beginning at either middle or old age, and assess its effects on blood glucose control. We find that either of the two genetic alterations in GH signaling ameliorates fasting hyperglycemia; additionally, both longevity-inducing somatotrophic mutations improve insulin sensitivity into old age. Strikingly, we observe major and broad improvements in blood glucose homeostatic control by IF: IF improves ad libitum-fed hyperglycemia, glucose tolerance, and insulin sensitivity, and reduces hepatic gluconeogenesis, in aging mutant and normal mice. These results on correction of aging-resultant blood glucose dysregulation have potentially important clinical and public health implications for our ever-graying global population, and are consistent with the Longevity Dividend concept.

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Acknowledgments

This work was supported by 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 especially thank Drs. Thomas A. Ala and Robert G. Struble.

Conflict of interest

The authors aver that they have no conflicts of interest related to this publication.

Authors’ contributions

O.A. and A.B.. acquired funding for this study; O.A. conceived and designed this study; O.A. and R.K.B. methodologically executed this study; O.A. statistically analyzed the data; O.A., J.K.S., R.K.K., and A.B.. prepared the manuscript for this study; and J.J.K. provided founder populations of some of the mice used for this study.

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

    Oge Arum, Jamal K. Saleh, Ravneet K. Boparai & 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. Department of Internal Medicine, Division of Endocrinology and Metabolism, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA, 23507, USA

    Romesh K. Khardori

  4. 631 N. 6th Street, 2B, Springfield, IL, 62702, USA

    Oge Arum

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  1. Oge Arum
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Correspondence to Oge Arum.

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Arum, O., Saleh, J.K., Boparai, R.K. et al. Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age. AGE 36, 9651 (2014). https://doi.org/10.1007/s11357-014-9651-2

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