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

Rizvi, Farhan; Preston, Claudia C.; Emelyanova, Larisa; Yousufuddin, Mohammed; Maria, Viqar; Dakwar, Omar; Ross, Gracious R.; Faustino, Randolph S.; Holmuhamedov, Ekhson; Jahangir, Arshad

doi:10.1161/jaha.120.019948

Cited by 42 publications

(21 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxidative stress is a major contributor to several age-associated cardiovascular diseases including atherosclerosis [ 27 , 91 , 92 ]. Gene expression coding for proteins involved in ROS production and clearance pathways are changed with aging in both human and rat hearts leading to increased systemic and cardiac oxidative stress and predisposing to cardiovascular diseases [ 9 , 93 ]. The responsiveness of the aged heart to stress is altered with a decrease in antioxidant capacity along with increased oxidant production [ 94 ].…”

Section: Oxidative Stress and Agingmentioning

confidence: 99%

The Role of Oxidative Stress in the Aging Heart

et al. 2022

View full text Add to dashboard Cite

Medical advances and the availability of diagnostic tools have considerably increased life expectancy and, consequently, the elderly segment of the world population. As age is a major risk factor in cardiovascular disease (CVD), it is critical to understand the changes in cardiac structure and function during the aging process. The phenotypes and molecular mechanisms of cardiac aging include several factors. An increase in oxidative stress is a major player in cardiac aging. Reactive oxygen species (ROS) production is an important mechanism for maintaining physiological processes; its generation is regulated by a system of antioxidant enzymes. Oxidative stress occurs from an imbalance between ROS production and antioxidant defenses resulting in the accumulation of free radicals. In the heart, ROS activate signaling pathways involved in myocyte hypertrophy, interstitial fibrosis, contractile dysfunction, and inflammation thereby affecting cell structure and function, and contributing to cardiac damage and remodeling. In this manuscript, we review recent published research on cardiac aging. We summarize the aging heart biology, highlighting key molecular pathways and cellular processes that underlie the redox signaling changes during aging. Main ROS sources, antioxidant defenses, and the role of dysfunctional mitochondria in the aging heart are addressed. As metabolism changes contribute to cardiac aging, we also comment on the most prevalent metabolic alterations. This review will help us to understand the mechanisms involved in the heart aging process and will provide a background for attractive molecular targets to prevent age-driven pathology of the heart. A greater understanding of the processes involved in cardiac aging may facilitate our ability to mitigate the escalating burden of CVD in older individuals and promote healthy cardiac aging.

show abstract

Section: Oxidative Stress and Agingmentioning

confidence: 99%

The Role of Oxidative Stress in the Aging Heart

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The most statistically significant age-related protein is SEPSECS (Figure 2C), Sep (Ophosphoserine) tRNA:Sec (selenocysteine) tRNA synthase, which has been associated with aging and cardiac oxidative stress (Rizvi et al 2021). Among the top 50 age-related proteins are genes in the mitochondrial respiratory complex I (NDUFA1), complex III (MT-CYTB, UQCRH), complex IV (COX7B), complex V (MT-ATP6), and other mitochondrial functions (OPA3, MRS2, CHCHD4, POLG); proteins involved in immune response (CD81, CD47); extracellular matrix remodelling (FERMT2, COL1A1, COL1A2); immunoglobulin chain components (IGHG2C, IGHA); protein-protein interaction (WDR65, ARVCF); actin cytoskeleton (ACTN3); autophagy and mitophagy (FAM134C, RABGEF1); and regulation of transcription and chromatin remodeling (ZFP947, HOPX, MED23, TRRAP) (Supplemental Data S2).…”

Section: Transcripts and Proteins Reveal Age-related Changes In Immun...mentioning

confidence: 99%

Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart

et al. 2022

View full text Add to dashboard Cite

Investigation of the molecular mechanisms of aging in the human heart is challenging due to confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12 and 18 months to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, while processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process.

show abstract

“…The data were from four independent experiments would affect ACE2 expression and cardiomyocyte senescence. Emerging evidence indicates that increased ROS generation contribute to age-related heart diseases [32]. H 2 O 2 has been the most commonly used inducer for stress-induced premature senescence in cardiac cells [33,34].…”

Section: Discussionmentioning

confidence: 99%

H2S protects from oxidative stress-driven ACE2 expression and cardiac aging

Barrow

Wang

et al. 2022

Mol Cell Biochem

View full text Add to dashboard Cite

Cystathionine gamma-lyase (CSE)-derived hydrogen sulfide (H 2 S) plays an essential role in preserving cardiac functions. Angiotensin-converting enzyme 2 (ACE2) acts as the negative regulator of the renin-angiotensin system, exerting antioxidative stress and anti-inflammatory properties within the body. The interplays of CSE/H 2 S signaling and ACE2 in cardiac aging are unclear. In this study, the regulatory roles of H 2 S on ACE2 expression in mouse heart tissue and rat cardiomyocytes under different stress conditions were investigated. It was found that ACE2 protein level was lower in heart tissues from old mice (56-week-old) than young mice (8-week-old), and the knockout of CSE (CSE KO) induced moderate oxidative stress and further inhibited ACE2 protein level in mouse hearts at both young and old age. Incubation of rat cardiac cells (H9C2) with a low dose of H 2 O 2 (50 µM) suppressed ACE2 protein level and induced cellular senescence, which was completely reversed by co-incubation with 30 µM NaHS (a H 2 S donor). Prolonged nutrient excess is an increased risk of heart disorders by causing metabolic dysfunction and cardiac remodeling. We further found high-fat diet feeding stimulated ACE2 expression and induced severe oxidative stress in CSE KO heart in comparison with wild-type heart. Lipid overload in H9C2 cells to mimic a status of nutrient excess also enhanced the expression of ACE2 protein and induced severe oxidative stress and cell senescence, which were significantly attenuated by the supplementation of exogenous H 2 S. Furthermore, the manipulation of ACE2 expression partially abolished the protective role of H 2 S against cellular senescence. These results demonstrate the dynamic roles of H 2 S in the maintenance of ACE2 levels under different levels of oxidative stress, pointing to the potential implications in targeting the CSE/H 2 S system for the interruption of aging and diabetes-related heart disorders.

show abstract

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

Cited by 42 publications

References 60 publications

The Role of Oxidative Stress in the Aging Heart

The Role of Oxidative Stress in the Aging Heart

Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart

H2S protects from oxidative stress-driven ACE2 expression and cardiac aging

Contact Info

Product

Resources

About