Senescence mechanisms and targets in the heart

Chen, Maggie; Lee, Richard T.; Garbern, Jessica C.

doi:10.1093/cvr/cvab161

Cited by 120 publications

(97 citation statements)

References 174 publications

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“…Some experimental studies have suggested that contractile function is also impaired with age [ 26 , 27 ]. Cardiac cycle duration is prolonged with an increase in both contraction and relaxation times.…”

Section: Aging Cardiac Changesmentioning

confidence: 99%

“…Several genetic, molecular and biochemical abnormalities are involved in the structural and functional myocardial changes during aging [ 9 , 26 , 35 , 36 , 37 ]. These abnormalities are mainly characterized by changes in contractile proteins and cardiac excitation-contraction coupling, decreased contractile response to β-adrenergic stimulation, increased systemic and myocardial oxidative stress and renin–angiotensin activity, and metabolic changes [ 3 , 26 , 27 ].…”

Section: Aging Cardiac Changesmentioning

confidence: 99%

“…Dysfunction in any of these mechanisms can disrupt redox homeostasis and increase oxidative stress [ 90 ]. 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 ].…”

Section: Oxidative Stress and Agingmentioning

confidence: 99%

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The Role of Oxidative Stress in the Aging Heart

et al. 2022

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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.

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Section: Aging Cardiac Changesmentioning

confidence: 99%

Section: Aging Cardiac Changesmentioning

confidence: 99%

Section: Oxidative Stress and Agingmentioning

confidence: 99%

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The Role of Oxidative Stress in the Aging Heart

et al. 2022

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“…Activation of the P53/P21 pathway is primarily triggered by telomere dysfunction and DNA damage (Donato et al, 2018). P21, a cyclin-dependent kinase inhibitor, is responsible for the initial cell cycle arrest at G1/S or G2/M (Chen et al, 2021). In contrast to apoptosis, senescent cells are stably viable and have the potential to produce or release a wide range of inflammatory cytokines and chemokines, termed SASP .…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging

Pan

Qin

et al. 2021

Front. Cell Dev. Biol.

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Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging.

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“…Telomere lengths consist of TTAGGG repeats in tandem that are reduced by multiple conditions including cellular aging, cellular senescence and apoptosis, cancer processes, heart and lung conditions, Alzheimer's disease, etc. [193][194][195][196][197][198][199][200]. Shorter telomeres have been described in PBMCs of PM males compared to controls or FM carriers, regardless of FXTAS or dementia diagnosis [201][202][203].…”

Section: Telomere Shortening In Premutation Carriersmentioning

confidence: 99%

Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes

Valor

Morales

Hervás-Corpión

et al. 2021

IJMS

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Abnormal trinucleotide expansions cause rare disorders that compromise quality of life and, in some cases, lifespan. In particular, the expansions of the CGG-repeats stretch at the 5’-UTR of the Fragile X Mental Retardation 1 (FMR1) gene have pleiotropic effects that lead to a variety of Fragile X-associated syndromes: the neurodevelopmental Fragile X syndrome (FXS) in children, the late-onset neurodegenerative disorder Fragile X-associated tremor-ataxia syndrome (FXTAS) that mainly affects adult men, the Fragile X-associated primary ovarian insufficiency (FXPOI) in adult women, and a variety of psychiatric and affective disorders that are under the term of Fragile X-associated neuropsychiatric disorders (FXAND). In this review, we will describe the pathological mechanisms of the adult “gain-of-function” syndromes that are mainly caused by the toxic actions of CGG RNA and FMRpolyG peptide. There have been intensive attempts to identify reliable peripheral biomarkers to assess disease progression and onset of specific pathological traits. Mitochondrial dysfunction, altered miRNA expression, endocrine system failure, and impairment of the GABAergic transmission are some of the affectations that are susceptible to be tracked using peripheral blood for monitoring of the motor, cognitive, psychiatric and reproductive impairment of the CGG-expansion carriers. We provided some illustrative examples from our own cohort. Understanding the association between molecular pathogenesis and biomarkers dynamics will improve effective prognosis and clinical management of CGG-expansion carriers.

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Senescence mechanisms and targets in the heart

Cited by 120 publications

References 174 publications

The Role of Oxidative Stress in the Aging Heart

The Role of Oxidative Stress in the Aging Heart

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging

Molecular Pathogenesis and Peripheral Monitoring of Adult Fragile X-Associated Syndromes

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