Analysis Tools
mortality/aging
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• mice exhibit sudden death between 28 and 35 days of age
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cellular
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• although individual mitochondria are formed with a normal number of cristae, inter-myofibrillar mitochondria are markedly disorganized in cardiac tissue
• numerous spherical electron dense inclusion bodies are observed within the mitochondria of cardiac cells
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• mitochondrial DNA copy number is reduced in cardiac tissue
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• citrate synthase activity is significantly reduced in cardiac homogenates, indicating a reduction in cardiac mitochondrial density
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• mitochondrial oxidative phosphorylation (OXPHOS) is significantly reduced in cardiac homogenates
• however, LEAK respiration is normal
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• mitochondrial electron transfer capacity (ETC) is significantly reduced in cardiac homogenates
• reduction in OXPHOS results in a lower respiratory control ratio (RCR) indicating that mitochondria are less efficient at producing ATP; effects are apparent regardless of which substrate is used for electron donation
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• cardiomyocytes show a burden of increased reactive oxygen species resulting from the action of deranged mitochondria
• induction of NRF, suggesting adaptation to conditions of oxidative stress
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cardiovascular system
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• mitochondrial DNA copy number is reduced in cardiac tissue
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• mice exhibit significant heart enlargement at P26
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• mice exhibit a significant heart weight to body weight ratio at P26
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• mice exhibit decreased left and right ventricle wall thickness at P26
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• mice exhibit significantly dilated heart ventricles at P26
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• heart left ventricle is significantly dilated at P26-P28, indicating systolic dysfunction
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• proteomics data revealed an upregulation of fibrosis markers in cardiac tissue
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• mice develop severe dilated cardiomyopathy with early stages of heart failure observed around 26-28 days of age
• however, no pulmonary or liver edema is observed
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• fractional shortening and relative wall thickness are significantly decreased at P26-P28
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• QRS interval is significantly shortened at P26-P28
• however, heart rate is normal
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• corrected QT (QTc) interval is significantly shortened at P26-P28
• however, the JT interval is normal
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homeostasis/metabolism
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• heart shows evidence for an attempted switch to glycolytic ATP generation, with induction of rate-limiting glycolytic enzyme genes
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• cardiac tissue recovered from P26 mice shows a significant reduction in the 18S/28S RNA ratio as well as a decrease in total protein concentration per cell
• mitochondria exhibit the largest loss of protein content, with small reciprocal increases seen in other compartments
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• citrate synthase activity is significantly reduced in cardiac homogenates, indicating a reduction in cardiac mitochondrial density
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growth/size/body
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• mice exhibit significant heart enlargement at P26
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• mice exhibit a significant heart weight to body weight ratio at P26
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muscle
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• mitochondrial DNA copy number is reduced in cardiac tissue
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• mice develop severe dilated cardiomyopathy with early stages of heart failure observed around 26-28 days of age
• however, no pulmonary or liver edema is observed
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• fractional shortening and relative wall thickness are significantly decreased at P26-P28
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