Document Detail

Telomeres and mitochondria in the aging heart.
MedLine Citation:
PMID:  22539756     Owner:  NLM     Status:  MEDLINE    
Studies in humans and in mice have highlighted the importance of short telomeres and impaired mitochondrial function in driving age-related functional decline in the heart. Although telomere and mitochondrial dysfunction have been viewed mainly in isolation, recent studies in telomerase-deficient mice have provided evidence for an intimate link between these two processes. Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and PGC-1β in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging.
Javid Moslehi; Ronald A DePinho; Ergün Sahin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Circulation research     Volume:  110     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-06-22     Revised Date:  2013-07-25    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1226-37     Citation Subset:  IM    
Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
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MeSH Terms
Age Factors
Aging / genetics*,  pathology
Cardiovascular Diseases / genetics*,  metabolism,  pathology
Carrier Proteins / metabolism
Energy Metabolism
Heat-Shock Proteins / metabolism
Mitochondria, Heart / metabolism*,  pathology
Signal Transduction
Telomerase / metabolism
Telomere / metabolism*,  ultrastructure
Telomere Shortening*
Transcription Factors / metabolism
Tumor Suppressor Protein p53 / metabolism
Grant Support
1U01CA141508-01/CA/NCI NIH HHS; K08HL097031/HL/NHLBI NIH HHS; R01 CA084628/CA/NCI NIH HHS; R01CA84628/CA/NCI NIH HHS
Reg. No./Substance:
0/Carrier Proteins; 0/Heat-Shock Proteins; 0/PPARGC1A protein, human; 0/PPARGC1B protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; EC

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