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C Conover, Endocrine Research Unit, Mayo Clinic, Rochester, United States
M Mason, Endocrine Research Unit, Mayo Clinic, Rochester, United States
J Levine, Endocrine Research Unit, Mayo Clinic, Rochester, United States
C Novak, Endocrine Research Unit, Mayo Clinic, Rochester, United States

Correspondence: Cheryl Conover, Email: conover.cheryl{at}mayo.edu

Abstract

Mice born with deletion of the gene for pregnancy associated plasma protein-A (PAPP-A), a model of reduced local insulin-like growth factor activity, live approximately 30% longer than their wild-type 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 knock-out (KO) mice compared to their wild-type 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 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.

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