Effects of Aging on Cardiac Oxidative Stress and Transcriptional Changes in Pathways of Reactive Oxygen Species Generation and Clearance

Autor: Larisa Emelyanova, Arshad Jahangir, Farhan Rizvi, Gracious R. Ross, Omar Dakwar, Mohammed Yousufuddin, Randolph S. Faustino, Maria Viqar, Claudia C. Preston, Ekhson Holmuhamedov
Rok vydání: 2021
Předmět:
Adult
Male
Aging
Adolescent
Transcription
Genetic
Physiology
Myocardial Biology
Mitochondrion
medicine.disease_cause
Mitochondria
Heart
Oxidative Phosphorylation
Molecular Cardiology
Young Adult
Superoxide Dismutase-1
Gene expression
Medicine
Animals
Humans
oxidative stress
Gene Regulatory Networks
Myocytes
Cardiac
Aged
Original Research
chemistry.chemical_classification
reactive oxygen species
Reactive oxygen species
Electron Transport Complex I
business.industry
Superoxide Dismutase
Age Factors
electron transport chain
Middle Aged
Electron transport chain
Rats
Inbred F344
Cell biology
Metabolism
chemistry
Reactive oxygen species generation
gene expression
Female
Lipid Peroxidation
Cardiology and Cardiovascular Medicine
business
Energy Metabolism
Transcriptome
Oxidant Stress
Oxidative stress
cardiac aging
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background Age‐related heart diseases are significant contributors to increased morbidity and mortality. Emerging evidence indicates that mitochondria within cardiomyocytes contribute to age‐related increased reactive oxygen species (ROS) generation that plays an essential role in aging‐associated cardiac diseases. Methods and Results The present study investigated differences between ROS production in cardiomyocytes isolated from adult (6 months) and aged (24 months) Fischer 344 rats, and in cardiac tissue of adult (18–65 years) and elderly (>65 years) patients with preserved cardiac function. Superoxide dismutase inhibitable ferricytochrome c reduction assay (1.32±0.63 versus 0.76±0.31 nMol/mg per minute; P =0.001) superoxide and H 2 O 2 production, measured as dichlorofluorescein diacetate fluorescence (1646±428 versus 699±329, P =0.04), were significantly higher in the aged versus adult cardiomyocytes. Similarity in age‐related alteration between rats and humans was identified in mitochondrial‐electron transport chain‐complex‐I‐associated increased oxidative‐stress by MitoSOX fluorescence (53.66±18.58 versus 22.81±12.60; P =0.03) and in 4‐HNE adduct levels (187.54±54.8 versus 47.83±16.7 ng/mg protein, P =0.0063), indicative of increased peroxidation in the elderly. These differences correlated with changes in functional enrichment of genes regulating ROS homeostasis pathways in aged human and rat hearts. Functional merged collective network and pathway enrichment analysis revealed common genes prioritized in human and rat aging‐associated networks that underlay enriched functional terms of mitochondrial complex I and common pathways in the aging human and rat heart. Conclusions Aging sensitizes mitochondrial and extramitochondrial mechanisms of ROS buildup within the heart. Network analysis of the transcriptome highlights the critical elements involved with aging‐related ROS homeostasis pathways common in rat and human hearts as targets.
Databáze: OpenAIRE
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