Longevity and Age-Related Pathology of Mice Deficient in Pregnancy-Associated Plasma Protein-A

The pregnancy-associated plasma protein-A knockout (PAPP-A KO) mouse is a model of reduced local insulin-like growth factor (IGF)-I activity with normal circulating IGF-I levels. In this study, PAPP-A KO mice had significantly increased mean (27%), median (27%), and maximum (35%) life span compared...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2010-06, Vol.65A (6), p.590-599
Main Authors: Conover, Cheryl A., Bale, Laurie K., Mader, Jessica R., Mason, Megan A., Keenan, Kevin P., Marler, Ronald J.
Format: Article
Language:English
Subjects:
Age Distribution
Aging - metabolism
Animals
Disease - etiology
Female
Gerontology
Incidence
Insulin-like growth factor I
Insulin-Like Growth Factor I - metabolism
Insulin-like growth factors
Journal of Gerontology: BIOLOGICAL SCIENCES
Kaplan-Meier Estimate
Longevity
Male
Mice
Mice, Inbred Strains
Mice, Knockout
Mouse model
Neoplasms - epidemiology
Pathology
Plasma
Pregnancy-associated plasma protein-A
Pregnancy-Associated Plasma Protein-A - deficiency
Proteins
Rodents
Studies
Tumors
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Summary:The pregnancy-associated plasma protein-A knockout (PAPP-A KO) mouse is a model of reduced local insulin-like growth factor (IGF)-I activity with normal circulating IGF-I levels. In this study, PAPP-A KO mice had significantly increased mean (27%), median (27%), and maximum (35%) life span compared with wild-type (WT) littermates. End-of-life pathology indicated that the incidence of neoplastic disease was not significantly different in the two groups of mice; however, it occurred in older aged PAPP-A KO compared with WT mice. Furthermore, PAPP-A KO mice were less likely to show degenerative changes of age. Scheduled pathologies at 78, 104, and 130 weeks of age indicated that WT mice, in general, had more degenerative changes and tumors earlier than PAPP-A KO mice. This was particularly true for abnormalities in heart, testes, brain, kidney, spleen, and thymus. In summary, the major contributors to the extended life span of PAPP-A KO mice are delayed occurrence of fatal neoplasias and decreased incidence of age-related degenerative changes.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glq032