Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria

Baohua Liu, Shrestha Ghosh, Xi Yang, Huiling Zheng, Xinguang Liu, Zimei Wang, Guoxiang Jin, Bojian Zheng, Brian K. Kennedy, Yousin Suh, Matt Kaeberlein, Karl Tryggvason, Zhongjun Zhou

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Abnormal splicing of LMNA gene or aberrant processing of prelamin A results in progeroid syndrome. Here we show that lamin A interacts with and activates SIRT1. SIRT1 exhibits reduced association with nuclear matrix (NM) and decreased deacetylase activity in the presence of progerin or prelamin A, leading to rapid depletion of adult stem cells (ASCs) in Zmpste24-/- mice. Resveratrol enhances the binding between SIRT1 and A-type lamins to increases its deacetylase activity. Resveratrol treatment rescues ASC decline, slows down body weight loss, improves trabecular bone structure and mineral density, and significantly extends the life span in Zmpste24-/- mice. Our data demonstrate lamin A as an activator of SIRT1 and provide a mechanistic explanation for the activation of SIRT1 by resveratrol. The link between conserved SIRT1 longevity pathway and progeria suggests a stem cell-based and SIRT1 pathway-dependent therapeutic strategy for progeria.

Original languageEnglish (US)
Pages (from-to)738-750
Number of pages13
JournalCell metabolism
Volume16
Issue number6
DOIs
StatePublished - Dec 5 2012

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Liu, B., Ghosh, S., Yang, X., Zheng, H., Liu, X., Wang, Z., Jin, G., Zheng, B., Kennedy, B. K., Suh, Y., Kaeberlein, M., Tryggvason, K., & Zhou, Z. (2012). Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell metabolism, 16(6), 738-750. https://doi.org/10.1016/j.cmet.2012.11.007