Faculty Collaboration Database

Effects of Aging on Cardiac Oxidative Stress and Transcriptional Changes in Pathways of Reactive Oxygen Species Generation and Clearance. J Am Heart Assoc 2021 Aug 17;10(16):e019948

Date

08/10/2021

Pubmed ID

34369184

Pubmed Central ID

PMC8475058

DOI

10.1161/JAHA.120.019948

Scopus ID

2-s2.0-85113262638 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

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 H₂O₂ 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.

Author List

Rizvi F, Preston CC, Emelyanova L, Yousufuddin M, Viqar M, Dakwar O, Ross GR, Faustino RS, Holmuhamedov EL, Jahangir A

Author

Gracious R. Ross Research Scientist II in the Cardiovascular Center department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Age Factors
Aged
Aging
Animals
Electron Transport Complex I
Energy Metabolism
Female
Gene Regulatory Networks
Humans
Lipid Peroxidation
Male
Middle Aged
Mitochondria, Heart
Myocytes, Cardiac
Oxidative Phosphorylation
Oxidative Stress
Rats
Rats, Inbred F344
Reactive Oxygen Species
Superoxide Dismutase
Superoxide Dismutase-1
Transcription, Genetic
Transcriptome
Young Adult