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 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.
Conover
Cheryl A
CA
The Division of Endocrinology and Metabolism, Department of Medicine, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, MN 55905, USA. Conover.Cheryl@mayo.edu
Bale
Laurie K
LK
Mader
Jessica R
JR
Mason
Megan A
MA
Keenan
Kevin P
KP
Marler
Ronald J
RJ
D017677:Age Distribution; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004194:Disease / Q000209:etiology*; D005260:Female; D015994:Incidence; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008136:Longevity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009369:Neoplasms / Q000453:epidemiology*; D011266:Pregnancy-Associated Plasma Protein-A / Q000172:deficiency*
D007334:Insulin-Like Growth Factor I; D011266:Pregnancy-Associated Plasma Protein-A