sFRP3 inhibition improves age-related cellular changes in BubR1 progeroid mice

Chang Hoon Cho, Ki Hyun Yoo, Alfredo Oliveros, Summer Paulson, Syed Mohammed Qasim Hussaini, Jan M. van Deursen, Mi Hyeon Jang

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Wnt signaling is a well-known molecular pathway in age-related pathogenesis and therapy of disease. While prior studies have mainly focused on Wnt ligands or Wnt activators, the in vivo functions of naturally secreted Wnt inhibitors are not clear, especially in brain aging. Using BubR1 H/H mice as a novel mouse model of accelerated aging, we report that genetic inhibition of sFRP3 restores the reduced body and brain size observed in BubR1 H/H mice. Furthermore, sFRP3 inhibition ameliorates hypomyelination in the corpus callosum and rescues neural progenitor proliferation in the hippocampal dentate gyrus of BubR1 H/H mice. Taken together, our study identifies sFRP3 as a new molecular factor that cooperates with BubR1 function to regulate brain development, myelination, and hippocampal neurogenesis.

Original languageEnglish (US)
Article numbere12899
JournalAging Cell
Volume18
Issue number2
DOIs
StatePublished - Apr 2019

Keywords

  • BubR1
  • myelination
  • neurogenesis
  • progeria
  • sFRP3

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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