Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: exploring possible relationship to the longevity phenotype

J Endocrinol. 2008 Sep;198(3):599-605. doi: 10.1677/JOE-08-0179. Epub 2008 Jun 19.

Abstract

Mice born with the deletion of the gene for pregnancy-associated plasma protein-A (PAPP-A), a model of reduced local IGF activity, live approximately 30% longer than their wild-type (WT) littermates. In this study, we investigated metabolic consequences of PAPP-A gene deletion and possible relationship to lifespan extension. Specifically, we determined whether 18-month-old PAPP-A knockout (KO) mice when compared with their WT littermates have reduced energy expenditure and/or altered glucose-insulin sensitivity. Food intake, and total energy expenditure and resting energy expenditure as measured by calorimetry were not different between PAPP-A KO and WT mice when subjected to the analysis of covariance with body weight as the covariate. However, there was an increase in spontaneous physical activity in PAPP-A KO mice. Both WT and PAPP-A KO mice exhibited mild insulin resistance with age, as assessed by fasting glucose/insulin ratios. Oral glucose tolerance and insulin sensitivity were not significantly different between the two groups of mice, although there appeared to be a decrease in the average size of the pancreatic islets in PAPP-A KO mice. Thus, neither reduced 'rate of living' nor altered glucose-insulin homeostasis can be considered key determinants of the enhanced longevity of PAPP-A KO mice. These findings are discussed in the context of those from other long-lived mouse models.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Eating
  • Energy Metabolism
  • Female
  • Glucose Tolerance Test
  • Immunohistochemistry
  • Longevity / genetics*
  • Male
  • Mice
  • Mice, Knockout
  • Pancreas / metabolism
  • Pregnancy-Associated Plasma Protein-A / genetics
  • Pregnancy-Associated Plasma Protein-A / physiology*

Substances

  • Pregnancy-Associated Plasma Protein-A