Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span

Laurie K. Bale, Sally A. West, Cheryl A Conover

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)895-897
Number of pages3
JournalAging Cell
Volume16
Issue number4
DOIs
StatePublished - Aug 1 2017

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Pregnancy-Associated Plasma Protein-A
Gene Expression
Tamoxifen
Mortality
Homologous Recombination
Gene Deletion
Embryonic Stem Cells
Life Expectancy
Knockout Mice

Keywords

  • adult mice
  • inducible gene knockout
  • lifespan
  • mortality rates
  • pregnancy-associated plasma protein-A
  • tamoxifen

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span. / Bale, Laurie K.; West, Sally A.; Conover, Cheryl A.

In: Aging Cell, Vol. 16, No. 4, 01.08.2017, p. 895-897.

Research output: Contribution to journalArticle

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