Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: exploring possible relationship to the longevity phenotype.
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.
Conover
Cheryl A
CA
Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA. conover@mayo.edu
Mason
Megan A
MA
Levine
James A
JA
Novak
Colleen M
CM
D000704:Analysis of Variance; D000818:Animals; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000502:physiology*
D011266:Pregnancy-Associated Plasma Protein-A