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

Age (Dordr). 2014 Jun;36(3):9651. doi: 10.1007/s11357-014-9651-2. Epub 2014 May 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Blood Glucose / metabolism*
  • Caloric Restriction
  • Energy Metabolism
  • Fasting / blood*
  • Female
  • Growth Hormone / deficiency*
  • Insulin / blood*
  • Insulin Resistance / physiology*
  • Longevity / physiology*
  • Male
  • Mice


  • Blood Glucose
  • Insulin
  • Growth Hormone