%0 Journal Article
%T Inducible knockdown of pregnancy©\associated plasma protein©\A gene expression in adult female mice extends life span
%A Laurie K. Bale
%A Sally A. West
%J Archive of "Aging Cell".
%D 2017
%R 10.1111/acel.12624
%X Pregnancy©\associated plasma protein©\A (PAPP©\A) knockout (KO) mice, generated through homologous recombination in embryonic stem cells, have a significantly increased lifespan compared to wild©\type littermates. However, it is unknown whether this longevity advantage would pertain to PAPP©\A gene deletion in adult animals. In the present study, we used tamoxifen (Tam)©\inducible Cre recombinase©\mediated excision of the floxed PAPP©\A (fPAPP©\A) gene in mice at 5 months of age. fPAPP©\A mice, which were either positive (pos) or negative (neg) for Tam©\Cre, received Tam treatment with quarterly boosters. Only female mice could be used with this experimental design. fPAPP©\A/neg and fPAPP©\A/pos mice had similar weights at the start of the experiment and showed equivalent weight gain. We found that fPAPP©\A/pos mice had a significant extension of life span (P = 0.005). The median life span was increased by 21% for fPAPP©\A/pos compared to fPAPP©\A/neg mice. Analysis of mortality in life span quartiles indicated that the proportion of deaths of fPAPP©\A/pos mice were lower than fPAPP©\A/neg mice at young adult ages (P = 0.002 for 601¨C800 days) and higher than fPAPP©\A/neg mice at older ages (P = 0.004 for >1000 days). Thus, survival curves and age©\specific mortality indicate that female mice with knockdown of PAPP©\A gene expression as adults have an extended healthy life span
%K adult mice
%K inducible gene knockout
%K lifespan
%K mortality rates
%K pregnancy©\associated plasma protein©\A
%K tamoxifen
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506424/