Metabolic consequences of pregnancy-associated plasma protein-A deficiency in mice: exploring possible relationship to the longevity phenotype
Year: 2008
Type: article
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.
Source: Journal of Endocrinology
DOI: 10.1677/joe-08-0179
Authors: Cheryl A Conover, Megan A Mason, James A Levine, Colleen M Novak
Institutions: Mayo Clinic, Arizona State University
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: bronze
Funders: Ellison Medical Foundation, American Heart Association, National Institutes of Health, U.S. Public Health Service, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Nutritional Restriction and Activity Thermogenesis, G2485550533, Instruments for measuring physical activity, G3485040570, G421583444, Heat Stroke & Hyperthermia: Applied Molecular Mechanisms, G4806712803, G4815040974, Depot-specific Adipogenesis in a Novel Mouse Model of Extended Lifespan, G628048870, Non-exercise Activity Thermogenesis (NEAT)
OpenAlex ID: W2101697574