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:	eng
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