Cellular senescence in cardiac diseases

Shimizu, Ippei; Minamino, Tohru

doi:10.1016/j.jjcc.2019.05.002

Cited by 118 publications

(95 citation statements)

References 71 publications

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“…Therefore, because incidence of CKD is high in older persons and age is considered the most consistent risk factor for CVDs (O'Hare et al, 2007;Elewa et al, 2012), CKD is often examined in the context of aging (Nitta et al, 2013). Furthermore, other fundamental mechanisms that characterize biological aging (López-Otín et al, 2013), such as cellular senescence, mitochondrial dysfunction, loss of proteostasis, or altered intercellular communication (López-Otín et al, 2013), may also play central roles in the pathogenesis of CKD-associated CVDs (Shimizu and Minamino, 2019). In this context, several studies have shown that CKD promotes cellular senescence and accelerates premature aging via diverse mechanisms in the internal milieu such as redox state perturbations, oxidative damage, inflammation, toxicity, and localized signaling mediated by growth factors (Stenvinkel and Larsson, 2013;Dai et al, 2019).…”

Section: Changes In Cellular Balance Of Reactive Oxygen Species Can Cmentioning

confidence: 99%

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremiaassociated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.

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Section: Changes In Cellular Balance Of Reactive Oxygen Species Can Cmentioning

confidence: 99%

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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“…Needless to say, the dysfunction of vasculature ECs is associated with aging and chronic diseases related to aging. This age-associated endothelial dysfunction is a critical antecedent of CVD [18]. Cellular senescence in adult human ECs is accompanied by increased basal oxidative stress, which is characterized by high reactive oxygen species (ROS) production and excessive pro-inflammatory cytokine release [133].…”

Section: Hif and Endothelial Cellsmentioning

confidence: 99%

“…This new concept, based on the studies of molecular mechanisms in the evolution of cellular senescence to avoid age-associated diseases, offers a new approach to secure the survival of senescent cells [1]. For this purpose, senotherapy (or senolysis) has been coined for therapies where senolytic drugs, which are intended to eliminate senescent cells by apoptosis [1,7,8,17,18], have shown beneficial effects in experimental models and human clinical trials [19][20][21][22][23]. Senolytic drugs may be useful as inhibitors of the progression of aging per se or disorders associated with premature aging, such as CVD [18,24,25].…”

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confidence: 99%

“…Moreover, in older normotensive people, aging produces higher arterial stiffness, systolic blood pressure, and pulse pressure [26,27]. These observations may be related to the increased accumulation of senescent cells in the vascular wall in aging or age-related CVD [18]. Indeed, vascular cellular senescence contributes to the pathogenesis of human arterial aging [28], and endothelial cell senescence has been reported to develop in heart failure and promote pathologic changes in a failing heart [8].…”

mentioning

confidence: 99%

“…Interestingly, once the p16 pathway is activated, senescence arrest cannot be reversed by the inactivation of p53 or the silencing of p16 [16]. A senescent cell uses a different process to achieve a senescent phenotype; therefore, this type of cell must be defined through various combinations of markers [18]. The structural and biological changes in the vascular walls that are linked to a specific mechanism in age-related changes of the vasculature are not yet well defined, mainly because they lack specific biomarkers for aging, which makes the study of vascular aging challenging.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Alique

Sánchez-López

Bodega

et al. 2020

Cells

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Aging is one of the hottest topics in biomedical research. Advances in research and medicine have helped to preserve human health, leading to an extension of life expectancy. However, the extension of life is an irreversible process that is accompanied by the development of aging-related conditions such as weakness, slower metabolism, and stiffness of vessels. It also debated that aging can be considered an actual disease with aging-derived comorbidities, including cancer or cardiovascular disease. Currently, cardiovascular disorders, including atherosclerosis, are considered as premature aging and represent the first causes of death in developed countries, accounting for 31% of annual deaths globally. Emerging evidence has identified hypoxia-inducible factor-1α as a critical transcription factor with an essential role in aging-related pathology, in particular, regulating cellular senescence associated with cardiovascular aging. In this review, we will focus on the regulation of senescence mediated by hypoxia-inducible factor-1α in age-related pathologies, with particular emphasis on the crosstalk between endothelial and vascular cells in age-associated atherosclerotic lesions. More specifically, we will focus on the characteristics and mechanisms by which cells within the vascular wall, including endothelial and vascular cells, achieve a senescent phenotype.

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Combined Endurance and Resistance Exercise Mitigates Age‐Associated Cardiac Dysfunction

Han,

Ashraf,

Shi

et al. 2024

Advanced Biology

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Aging is associated with a decline in cardiac function. Exercise has been shown to effectively reduce the risks of cardiovascular diseases. Here whether a combination of endurance and resistance exercises can improve cardiac function in aged mice during late life is investigated. Through transcriptome analysis, several signaling pathways activated in the hearts of 22‐month‐old mice after combined exercise, including cardiac muscle contraction, mitophagy, and longevity regulation are identified. Combined exercise training mitigated age‐associated pathological cardiac hypertrophy, reduced oxidative stress, cardiac senescence, and enhanced cardiac function. Upstream stimulatory factor 2 (Usf2) is upregulated in the aged mouse hearts with combined exercise compared to sedentary mice. In the human cardiomyocytes senescent model, overexpression of Usf2 led to anti‐senescence effects, while knockdown of Usf2 exacerbated cellular senescence. The results suggest that a combination of endurance and resistance exercises, such as swimming and resistance running, can mitigate age‐related pathological cardiac remodeling and cardiac dysfunction in late life. These cardioprotective effects are likely due to the activation of Usf2 and its anti‐senescence effect. Therefore, Usf2 can potentially be a novel therapeutic target for mitigating age‐related cardiac dysfunction.

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Cellular senescence in cardiac diseases

Cited by 118 publications

References 71 publications

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Combined Endurance and Resistance Exercise Mitigates Age‐Associated Cardiac Dysfunction

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