Journal article
Overexpression of Catalase Targeted to Mitochondria Attenuates Murine Cardiac Aging
Circulation (New York, N.Y.), Vol.119(21), pp.2789-2797
2009
DOI: 10.1161/CIRCULATIONAHA.108.822403
PMCID: PMC2858759
PMID: 19451351
Abstract
Background: Age is a major risk for cardiovascular diseases. Although mitochondrial reactive oxygen species have been proposed as one of the causes of aging, their role in cardiac aging remains unclear. We have previously shown that overexpression of catalase targeted to mitochondria (mCAT) prolongs murine median lifespan by 17% to 21%.
Methods and results: We used echocardiography to study cardiac function in aging cohorts of wild-type and mCAT mice. Changes found in wild-type mice recapitulate human aging: age-dependent increases in left ventricular mass index and left atrial dimension, worsening of the myocardial performance index, and a decline in diastolic function. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations and deletions and mitochondrial biogenesis, increased ventricular fibrosis, enlarged myocardial fiber size, decreased cardiac SERCA2 protein, and activation of the calcineurin-nuclear factor of activated T-cell pathway. All of these age-related changes were significantly attenuated in mCAT mice. Analysis of survival of 130 mice demonstrated that echocardiographic cardiac aging risk scores were significant predictors of mortality. The estimated attributable risk to mortality for these 2 parameters was 55%.
Conclusions: This study shows that cardiac aging in the mouse closely recapitulates human aging and demonstrates the critical role of mitochondrial reactive oxygen species in cardiac aging and the impact of cardiac aging on survival. These findings also support the potential application of mitochondrial antioxidants in reactive oxygen species-related cardiovascular diseases.
Details
- Title: Subtitle
- Overexpression of Catalase Targeted to Mitochondria Attenuates Murine Cardiac Aging
- Creators
- Dao-Fu DAI - Department of Pathology, University of Washington, Seattle, United StatesLuis F SANTANA - Department of Physiology and Biophysics, University of Washington, Seattle, United StatesPeter S RABINOVITCH - Department of Pathology, University of Washington, Seattle, United StatesMarc VERMULST - Department of Pathology, University of Washington, Seattle, United StatesDaniela M TOMAZELA - Department of Genome Sciences, University of Washington, Seattle, United StatesMary J EMOND - Department of Biostatistics, University of Washington, Seattle, United StatesMichael J MACCOSS - Department of Genome Sciences, University of Washington, Seattle, United StatesKatherine GOLLAHON - Department of Pathology, University of Washington, Seattle, United StatesGeorge M MARTIN - Department of Pathology, University of Washington, Seattle, United StatesLawrence A LOEB - Department of Pathology, University of Washington, Seattle, United StatesWarren C LADIGES - Department of Comparative Medicine, University of Washington, Seattle, United States
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.119(21), pp.2789-2797
- DOI
- 10.1161/CIRCULATIONAHA.108.822403
- PMID
- 19451351
- PMCID
- PMC2858759
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2009
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984047638302771
Metrics
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