| Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. | |
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MedLine Citation:
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PMID: 23217256 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell metabolism Volume: 16 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: 2013-05-22 Revised Date: 2013-06-03 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 738-50 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong. ppliew@hku.hk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Stem Cells
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cytology,
drug effects*,
metabolism Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Cell Line Enzyme Activation / drug effects HEK293 Cells Humans Lamin Type A / genetics, metabolism* Longevity Membrane Proteins / deficiency, genetics, metabolism Metalloendopeptidases / deficiency, genetics, metabolism Mice 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* |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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