Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span.
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 601-800 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.
['Bale|Laurie K|LK|', 'West|Sally A|SA|', 'Conover|Cheryl A|CA|']
D000818:Animals D001835:Body Weight D005260:Female D015870:Gene Expression D055785:Gene Knockdown Techniques D019426:Integrases D008136:Longevity D051379:Mice D018345:Mice, Knockout D011247:Pregnancy D011266:Pregnancy-Associated Plasma Protein-A D016019:Survival Analysis D013629:Tamoxifen
pregnancy-associated plasma protein-A lifespan tamoxifen adult mice inducible gene knockout mortality rates