Document Detail

Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria.
MedLine Citation:
PMID:  23217256     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell metabolism     Volume:  16     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-22     Revised Date:  2014-10-19    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  738-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Adult Stem Cells / cytology,  drug effects*,  metabolism
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Line
Enzyme Activation / drug effects
HEK293 Cells
Lamin Type A / genetics,  metabolism*
Membrane Proteins / deficiency,  genetics,  metabolism
Metalloendopeptidases / deficiency,  genetics,  metabolism
Mice, Knockout
Nuclear Matrix / metabolism
Nuclear Proteins / metabolism
Progeria / metabolism,  pathology*
Protein Binding
Protein Precursors / metabolism
Recombinant Proteins / biosynthesis,  genetics,  pharmacology
Sirtuin 1 / genetics,  metabolism*
Stilbenes / pharmacology*
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Lamin Type A; 0/Membrane Proteins; 0/Nuclear Proteins; 0/Protein Precursors; 0/Recombinant Proteins; 0/Stilbenes; 0/prelamin A; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/Zmpste24 protein, mouse; EC 3.5.1.-/Sirtuin 1; Q369O8926L/resveratrol

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