TY - JOUR
T1 - Longevity and age-related pathology of mice deficient in pregnancy-associated plasma protein-a
AU - Conover, Cheryl A.
AU - Bale, Laurie K.
AU - Mader, Jessica R.
AU - Mason, Megan A.
AU - Keenan, Kevin P.
AU - Marler, Ronald J.
N1 - Funding Information:
this work was supported by the national institute (r01ag028141) and the ellison Medical Foundation.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Insulin-like growth factor I
KW - Longevity
KW - Mouse model
KW - Pathology
KW - Pregnancy-associated plasma protein-A
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U2 - 10.1093/gerona/glq032
DO - 10.1093/gerona/glq032
M3 - Article
C2 - 20351075
AN - SCOPUS:77953015038
SN - 1079-5006
VL - 65 A
SP - 590
EP - 599
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 6
ER -