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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0179v1 198/3/599    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Conover, C. A Articles by Novak, C. M Search for Related Content PubMed PubMed Citation Articles by Conover, C. A Articles by Novak, C. M

Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA

(Correspondence should be addressed to C A Conover; Email: conover{at}mayo.edu)

Mice born with the deletion of the gene for pregnancy-associated plasma protein-A (PAPP-A), a model of reduced local IGF activity, live 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.