Targeting senescent cells to attenuate cardiovascular disease progression DOI Creative Commons

Ping Song,

Qiang Zhao,

Ming-Hui Zou

et al.

Ageing Research Reviews, Journal Year: 2020, Volume and Issue: 60, P. 101072 - 101072

Published: April 14, 2020

Cardiovascular disease (CVD) is the most common to increase as life expectancy increases. Most high-profile pharmacological treatments for age-related CVD have led inefficacious results, implying that novel approaches treating these pathologies are needed. Emerging data demonstrated senescent cardiovascular cells, which characterized by irreversible cell cycle arrest and a distinct senescence-associated secretory phenotype, accumulate in aged or diseased systems, suggesting they may impair function. This review discusses evidence implicating cells ageing, onset progression of CVD, molecular mechanisms underlying senescence. We also eradication small-molecule-drug-mediated apoptosis immune cell-mediated efferocytosis toxicity promising precisely targeted therapeutics prevention treatment.

Language: Английский

The role of cellular senescence in cardiac disease: basic biology and clinical relevance DOI

Mozhdeh Mehdizadeh,

Martín Aguilar, Éric Thorin

et al.

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 19(4), P. 250 - 264

Published: Oct. 19, 2021

Language: Английский

Citations

186
Senescence mechanisms and targets in the heart DOI Open Access
Maggie Chen, Richard Lee, Jessica C. Garbern

et al.

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(5), P. 1173 - 1187

Published: May 5, 2021

Abstract Cellular senescence is a state of irreversible cell cycle arrest associated with ageing. Senescence different cardiac types can direct the pathophysiology cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and fibrosis. While age-related telomere shortening represents major cause replicative senescence, senescent also be induced by oxidative stress, metabolic dysfunction, epigenetic regulation, among other stressors. It critical that we understand molecular pathways lead to cellular consequences in order develop new therapeutic approaches treat CVD. In this review, discuss mechanisms explore how (including cardiomyocytes, endothelial cells, fibroblasts, vascular smooth muscle valve interstitial cells) CVD, highlight potential target prevent or

Language: Английский

Citations

170
Cardiomyocyte Senescence and Cellular Communications Within Myocardial Microenvironments DOI Creative Commons
Xiaoqiang Tang, Peiheng Li, Hou‐Zao Chen

et al.

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: May 21, 2020

Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging associated with maladaptation cellular metabolism, dysfunction (or senescence) cardiomyocytes, a decrease in angiogenesis, and increase tissue scarring (fibrosis). These events eventually lead to cardiac remodeling failure. Senescent cardiomyocytes show hallmarks DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile hypertrophic growth, senescence-associated secreting phenotype (SASP). Metabolism within essential not only fuel pump function heart but also maintain functional homeostasis participate senescence cardiomyocytes. The cardiomyocyte regulated by non-myocytes (endothelial cells, fibroblasts, immune cells) local microenvironment. On other hand, senescent alter their phenotypes subsequently affect microenvironment contribute pathological remodeling. In this review, we first summarized Then, discussed metabolic switch provided discussion communications between dysfunctional We addressed functions regulators modulating myocardial Finally, pointed out some interesting important questions that are needed be further studies.

Language: Английский

Citations

157
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases DOI Creative Commons

Ping Song,

Junqing An,

Ming-Hui Zou

et al.

Cells, Journal Year: 2020, Volume and Issue: 9(3), P. 671 - 671

Published: March 10, 2020

Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, apoptotic resistance in multiple organs due to various stressors. Excessive accumulation of senescent numerous tissues leads chronic diseases, tissue dysfunction, age-related diseases organ ageing. Immune can remove cells. Immunaging or impaired innate adaptive immune responses result persistent Although senolytics—drugs that selectively inducing their apoptosis—are recent hot topics making significant research progress, senescence immunotherapies using cell-mediated clearance emerging promising strategies fight ageing diseases. This short review provides an overview the progress date concerning cell-caused ageing, as well regulation small-molecule drugs clinical trials different roles elimination Mounting evidence indicates immunotherapy targeting combats subsequently extends healthy lifespan.

Language: Английский

Citations

154
Hallmarks of cardiovascular ageing DOI
Mahmoud Abdellatif, Peter P. Rainer, Simon Sedej

et al.

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(11), P. 754 - 777

Published: May 16, 2023

Language: Английский

Citations

119
Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence DOI Creative Commons
Yinsheng Wu, Lixu Tang, Han Huang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 10, 2023

Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about role senescence. Here, we report a critical glycolysis-derived serine biosynthesis preventing During senescence, expression biosynthetic enzyme PHGDH significantly reduced due to decreased transcription activating factor ATF4, which leads reduction intracellular serine. prevents premature primarily by enhancing stability and activity pyruvate kinase M2 (PKM2). Mechanistically, interacts PKM2, PCAF-catalyzed PKM2 K305 acetylation subsequent degradation autophagy. In addition, facilitates p300-catalyzed K433 acetylation, promotes nuclear translocation stimulates its phosphorylate H3T11 regulate senescence-associated genes. endothelium-targeted ameliorates mice. Our findings reveal that could become therapy promote healthy ageing.

Language: Английский

Citations

55
Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets DOI Creative Commons
Yi Luan, Xiaofan Zhu,

Yuxue Jiao

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 14, 2024

Abstract Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even people without prior history of disease. To address this issue and improve function, it crucial investigate the molecular mechanisms underlying senescence. This review summarizes main key proteins involved further discusses modulators cellular senescence aging hearts. Furthermore, discussion will encompass comprehensive descriptions drugs, modes action potential targets for intervention By offering fresh perspective insights into seeks provide important theoretical foundations development drugs targeting condition.

Language: Английский

Citations

26
Unveiling the Role of Inflammation and Oxidative Stress on Age-Related Cardiovascular Diseases DOI Creative Commons
Arthur José Pontes Oliveira de Almeida,

Mathania Silva de Almeida Rezende,

Sabine Helena Dantas

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 20

Published: May 9, 2020

The global population above 60 years has been growing exponentially in the last decades, which is accompanied by an increase prevalence of age-related chronic diseases, highlighting cardiovascular diseases (CVDs), such as hypertension, atherosclerosis, and heart failure. Aging main risk factor for these diseases. Such susceptibility to disease explained, at least part, oxidative stress, it damages cellular components proteins, DNA, lipids. In addition, inflammatory process aging “inflammaging” also contributes cell damage, creating a stressful environment drives development CVDs. Taken together, possible identify molecular connection between stress process, especially crosstalk transcription factors Nrf-2 NF- κ B are mediated redox signalling involved aging. Therapies that control this key targets prevention/combat review, we show basics inflammation including them, implications on

Language: Английский

Citations

133
Single-cell transcriptomic atlas of primate cardiopulmonary aging DOI Creative Commons
Shuai Ma, Shuhui Sun, Jiaming Li

et al.

Cell Research, Journal Year: 2020, Volume and Issue: 31(4), P. 415 - 432

Published: Sept. 10, 2020

Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular molecular mechanisms associated with aging higher mammals therefore urgently needed. Here, we created young old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart artery, the top tissues targeted by SARS-CoV-2. Analysis cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation compromised virus defense as hallmark aging. With age, expression SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was pulmonary alveolar epithelial barrier, cardiomyocytes, vascular endothelial cells. We found that interleukin 7 (IL7) accumulated aged induced ACE2 human cells an NF-κB-dependent manner. Furthermore, treatment vitamin C blocked IL7-induced expression. Altogether, our findings depict first atlas system provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting geroprotective strategies may reduce COVID-19 severity elderly.

Language: Английский

Citations

119
Targeting Age-Related Pathways in Heart Failure DOI Open Access
Haobo Li, Margaret H. Hastings, James Rhee

et al.

Circulation Research, Journal Year: 2020, Volume and Issue: 126(4), P. 533 - 551

Published: Feb. 13, 2020

During aging, deterioration in cardiac structure and function leads to increased susceptibility heart failure. The need for interventions combat this age-related decline is becoming increasingly urgent as the elderly population continues grow. Our understanding of aging general, limited. However, recent studies its prevention through like exercise have revealed novel pathological cardioprotective pathways. In review, we summarize findings concerning molecular mechanisms failure highlight a valuable experimental platform discovery much-needed therapeutic targets chronic disease.

Language: Английский

Citations

112