The journal of cardiovascular aging最新文献_第2页

IF 4.4

The journal of cardiovascular aging Pub Date : 2025-01-01 Epub Date: 2025-07-08 DOI: 10.20517/jca.2024.29

Nicholas W Chavkin

{"title":"Age-related cardiovascular disease and mosaic hematopoietic loss of the Y chromosome.","authors":"Nicholas W Chavkin","doi":"10.20517/jca.2024.29","DOIUrl":"10.20517/jca.2024.29","url":null,"abstract":"Age is the strongest risk factor for cardiovascular morbidity and mortality, driven in part by aging leukocytes negatively impact cardiovascular health. This effect is particularly pronounced in men, who have a shorter average lifespan-approximately six years less than women, largely due to higher mortality rates in old age. One contributing factor is a male-specific aging blood phenotype characterized by the mosaic loss of the Y chromosome (mLOY), a condition in which a subset of blood cells lose the Y chromosome. mLOY is highly prevalent in elderly men, affecting 45% of those aged 70 and older. Recent studies have linked mLOY to increased early mortality, age-related pathologies, and cardiovascular disease, potentially explaining the observed sex discrepancy in life expectancy. Experimental studies have begun to uncover potential mechanisms related to leukocyte responses to cardiac injury and the polarization of macrophages that promote pro-fibrotic cytokine expression. Current evidence suggests that mLOY reflects an underlying aspect of biological aging related to genomic instability, which drives age-related diseases, including cardiovascular conditions. Although mLOY shares similarities with general age-related changes in the hematopoietic system, it may exert distinct effects on leukocytes that promote cardiovascular disease through enhanced tissue fibrosis pathways. These findings highlight that mLOY accumulates with age and contributes to cardiovascular disease through mechanisms that are independent of biological aging per se. Further investigation into mLOY-specific pathways in aging and age-related diseases may reveal novel therapeutic targets for a chronic condition that affects a large proportion of the elderly male population. This review discusses the current literature on mLOY and its connection to cardiovascular disease within the broader context of aging.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"5 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13330738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure. 心力衰竭中的老年科学：在人类衰老和心力衰竭的共同病理生物学中寻找治疗靶点。

IF 4.4

The journal of cardiovascular aging Pub Date : 2025-01-01 Epub Date: 2025-01-14 DOI: 10.20517/jca.2024.15

Claire Castro, Constance Delwarde, Yanxi Shi, Jason Roh

{"title":"Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure.","authors":"Claire Castro, Constance Delwarde, Yanxi Shi, Jason Roh","doi":"10.20517/jca.2024.15","DOIUrl":"10.20517/jca.2024.15","url":null,"abstract":"Age is a major risk factor for heart failure, but one that has been historically viewed as non-modifiable. Emerging evidence suggests that the biology of aging is malleable, and can potentially be intervened upon to treat age-associated chronic diseases, such as heart failure. While aging biology represents a new frontier for therapeutic target discovery in heart failure, the challenges of translating Geroscience research to the clinic are multifold. In this review, we propose a strategy that prioritizes initial target discovery in human biology. We review the rationale for starting with human omics, which has generated important insights into the shared (patho)biology of human aging and heart failure. We then discuss how this knowledge can be leveraged to identify the mechanisms of aging biology most relevant to heart failure. Lastly, we provide examples of how this human-first Geroscience approach, when paired with rigorous functional assessments in preclinical models, is leading to early-stage clinical development of gerotherapeutic approaches for heart failure.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"5 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aging diastole - root cause for atrial fibrillation and heart failure with preserved ejection fraction. 衰老性舒张：保留射血分数的心房颤动和心力衰竭的根本原因。

IF 3

The journal of cardiovascular aging Pub Date : 2024-12-01 Epub Date: 2024-12-23 DOI: 10.20517/jca.2024.22

Markus Meyer, Julio Núñez, Parag Goyal, Daniel N Silverman, Jop H van Berlo, Valmiki Maharaj

引用次数: 0

Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential. 房颤进展的衰老相关机制及其治疗潜力。

IF 3

The journal of cardiovascular aging Pub Date : 2024-12-01 Epub Date: 2024-11-07 DOI: 10.20517/jca.2024.12

Shuai Zhao, Aaron M Johnston, Chi Him Kendrick Yiu, Lucia M Moreira, Svetlana Reilly, Xander H T Wehrens

引用次数: 0

The aging heart: exploring the role of Klotho in cardiac health/function. 老化的心脏：探索Klotho在心脏健康/功能中的作用。

IF 3

The journal of cardiovascular aging Pub Date : 2024-12-01 Epub Date: 2024-12-19 DOI: 10.20517/jca.2024.16

Nastaran Daneshgar, Dao-Fu Dai, Chad E Grueter

引用次数: 0

Microvascular angiotensin II type 2 receptor function is enhanced in young females and declines in a model of murine aging. 微血管紧张素II型2受体功能在年轻女性中增强，在小鼠衰老模型中下降。

IF 3

The journal of cardiovascular aging Pub Date : 2024-07-01 Epub Date: 2024-08-14 DOI: 10.20517/jca.2024.09

Casey G Turner, Karla de Oliveira, Qing Lu, Ayan R Patel, Lakshmi Pulakat, Iris Z Jaffe, Jennifer J DuPont

{"title":"Microvascular angiotensin II type 2 receptor function is enhanced in young females and declines in a model of murine aging.","authors":"Casey G Turner, Karla de Oliveira, Qing Lu, Ayan R Patel, Lakshmi Pulakat, Iris Z Jaffe, Jennifer J DuPont","doi":"10.20517/jca.2024.09","DOIUrl":"10.20517/jca.2024.09","url":null,"abstract":"Introduction: Angiotensin II (AngII) affects cardiovascular health, mediating impacts through AngII type 1 (AT1R) and type 2 (AT2R) receptors. The present study investigated sex and aging-related differences in microvascular AngII receptor function in mice and humans.Methods: Mesenteric resistance arteries (MRA) were isolated from 3-, 12-, and 18-month-old female and male C57/Bl6 mice. Wire myography was used to measure vasoconstriction to AngII and vasodilation to an AT2R agonist (compound 21, C21). Seven healthy adults (3 premenopausal women and 4 age-matched men) were recruited to participate in a study measuring cutaneous microvascular vasoconstriction to AngII in the presence and absence of 10 μM PD123319, an AT2R antagonist.Results: In murine MRA, AngII-induced constriction increases by 18 months in females and by 12 months in males. AT2R-mediated vasodilation was reduced with age in females only, which corresponds with a female-specific decrease in mesenteric AT2R mRNA expression. AT2R inhibition enhances AngII-induced constriction in young female, but not male, mice. Clinical data support that premenopausal women have attenuated AngII constriction vs. men, which is abrogated by AT2R inhibition. AT2R expression is greater in primary aortic smooth muscle cells, but not endothelial cells, from young women compared with men.Conclusions: These data demonstrate enhanced microvascular AT2R function in young female mice and young women. There is a female-specific loss of AT2R function with age in mice, concomitant with declining AT2R expression. These findings implicate AT2R as a sex-specific target for microvascular dysfunction and aging-associated cardiovascular disease.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12030185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiomyocyte senescence and the potential therapeutic role of senolytics in the heart 心肌细胞衰老和衰老素对心脏的潜在治疗作用

The journal of cardiovascular aging Pub Date : 2024-06-03 DOI: 10.20517/jca.2024.06

P. Zhai, J. Sadoshima

{"title":"Cardiomyocyte senescence and the potential therapeutic role of senolytics in the heart","authors":"P. Zhai, J. Sadoshima","doi":"10.20517/jca.2024.06","DOIUrl":"https://doi.org/10.20517/jca.2024.06","url":null,"abstract":"Cellular senescence in cardiomyocytes, characterized by cell cycle arrest, resistance to apoptosis, and the senescence-associated secretory phenotype, occurs during aging and in response to various stresses, such as hypoxia/reoxygenation, ischemia/reperfusion, myocardial infarction (MI), pressure overload, doxorubicin treatment, angiotensin II, diabetes, and thoracic irradiation. Senescence in the heart has both beneficial and detrimental effects. Premature senescence of myofibroblasts has salutary effects during MI and pressure overload. On the other hand, persistent activation of senescence in cardiomyocytes precipitates cardiac dysfunction and adverse remodeling through paracrine mechanisms during MI, myocardial ischemia/reperfusion, aging, and doxorubicin-induced cardiomyopathy. Given the adverse roles of senescence in many conditions, specific removal of senescent cells, i.e., senolysis, is of great interest. Senolysis can be achieved using senolytic drugs (such as Navitoclax, Dasatinib, and Quercetin), pharmacogenetic approaches (including INK-ATTAC and AP20187, p16-3MR and Ganciclovir, p16 ablation, and p16-LOX-ATTAC and Cre), and immunogenetic interventions (CAR T cells or senolytic vaccination). In order to enhance the specificity and decrease the off-target effects of senolytic approaches, investigation into the mechanisms through which cardiomyocytes develop and/or maintain the senescent state is needed.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"115 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141271950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysfunctional mitochondria elicit bioenergetic decline in the aged heart. 线粒体功能失调导致老年心脏生物能下降。

The journal of cardiovascular aging Pub Date : 2024-04-01 Epub Date: 2024-02-01 DOI: 10.20517/jca.2023.50

Pasquale Mone, Esther Densu Agyapong, Giampaolo Morciano, Stanislovas S Jankauskas, Antonio De Luca, Fahimeh Varzideh, Paolo Pinton, Gaetano Santulli

引用次数: 0

Targeting vascular senescence in cardiovascular disease with aging. 针对心血管疾病中的血管衰老与衰老。

The journal of cardiovascular aging Pub Date : 2024-04-01 Epub Date: 2024-02-28 DOI: 10.20517/jca.2023.45

Shelby A Hall, Lisa A Lesniewski

{"title":"Targeting vascular senescence in cardiovascular disease with aging.","authors":"Shelby A Hall, Lisa A Lesniewski","doi":"10.20517/jca.2023.45","DOIUrl":"10.20517/jca.2023.45","url":null,"abstract":"Aging is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Two major age-associated arterial phenotypes, endothelial dysfunction and large elastic arterial stiffness, are autonomous predictors of future CVD diagnosis and contribute to the progression of CVD in older adults. Senescent cells lose the capacity to proliferate but remain metabolically active and secrete inflammatory factors termed senescence-associated secretory phenotype (SASP), leading to an increase in inflammation and oxidative stress. Accumulation of senescent cells is linked with the progression of age-related diseases and has been known to play a role in cardiovascular disease. In this brief review, we describe the characteristics and mechanisms of senescent cell accumulation and how senescent cells promote endothelial dysfunction and arterial stiffness. We focus on a range of novel therapeutic strategies aimed at reducing the burden of endothelial dysfunction leading to atherosclerosis through targeting senescent cells. Studies have begun to investigate a specific class of drugs that are able to selectively eliminate senescent cells, termed senolytics, which have shown great promise in reversing the aging phenotype and ameliorating pathologies in age-related disorders, creating a new opportunity for aging research. Generating therapies targeting the elimination of senescent cells would improve health span and increase longevity, making senolytics a promising therapy for cardiovascular diseases.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of brown adipose tissue in mediating healthful longevity. 棕色脂肪组织在调解健康长寿中的作用。

IF 4.4

The journal of cardiovascular aging Pub Date : 2024-04-01 Epub Date: 2024-04-27 DOI: 10.20517/jca.2024.01

Jie Zhang, Berhanu Geresu Kibret, Dorothy E Vatner, Stephen F Vatner

{"title":"The role of brown adipose tissue in mediating healthful longevity.","authors":"Jie Zhang, Berhanu Geresu Kibret, Dorothy E Vatner, Stephen F Vatner","doi":"10.20517/jca.2024.01","DOIUrl":"10.20517/jca.2024.01","url":null,"abstract":"There are two major subtypes of adipose tissue, i.e., white adipose tissue (WAT) and brown adipose tissue (BAT). It has been known for a long time that WAT mediates obesity and impairs healthful longevity. More recently, interest has focused on BAT, which, unlike WAT, actually augments healthful aging. The goal of this review is to examine the role of BAT in mediating healthful longevity. A major role for BAT and its related beige adipose tissue is thermogenesis, as a mechanism to maintain body temperature by producing heat through uncoupling protein 1 (UCP1) or through UCP1-independent thermogenic pathways. Our hypothesis is that healthful longevity is, in part, mediated by BAT. BAT protects against the major causes of impaired healthful longevity, i.e., obesity, diabetes, cardiovascular disorders, cancer, Alzheimer's disease, reduced exercise tolerance, and impaired blood flow. Several genetically engineered mouse models have shown that BAT enhances healthful aging and that their BAT is more potent than wild-type (WT) BAT. For example, when BAT, which increases longevity and exercise performance in mice with disruption of the regulator of G protein signaling 14 (RGS14), is transplanted to WT mice, their exercise capacity is enhanced at 3 days after BAT transplantation, whereas BAT transplantation from WT to WT mice also resulted in increased exercise performance, but only at 8 weeks after transplantation. In view of the ability of BAT to mediate healthful longevity, it is likely that a pharmaceutical analog of BAT will become a novel therapeutic modality.","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"4 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11309368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0