Mechanisms and consequences of endothelial cell senescence

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(1), P. 38 - 51

Published: July 19, 2022

Language: Английский

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Hallmarks of cardiovascular ageing

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

Published: May 16, 2023

Language: Английский

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Aging impairs the neurovascular interface in the heart

Science, Journal Year: 2023, Volume and Issue: 381(6660), P. 897 - 906

Published: Aug. 24, 2023

Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed impact of on cardiac neurovascular interface. We report that reduces nerve density in ventricle dysregulates vascular-derived neuroregulatory genes. down-regulates microRNA 145 (miR-145) derepresses neurorepulsive semaphorin-3A. miR-145 deletion, which increased

Language: Английский

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Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 353 - 353

Published: Feb. 17, 2024

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are primary cause death worldwide, with an immense impact on patient quality life and disability. According to World Health Organization, CVD takes estimated 17.9 million lives each year, where more than four out five deaths due attacks strokes. In decades come, increased prevalence age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular disease, failure (HF) will contribute even greater health economic burden global average expectancy increases consequently world’s population continues age. Considering this, it is important focus our research efforts understanding fundamental mechanisms underlying CVD. this review, we cellular senescence mitochondrial dysfunction, which have long been established We also assess recent advances in targeting dysfunction including energy starvation oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, therapies that influence both therefore perhaps represent strategies most clinical potential, range, utility.

Language: Английский

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Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group

The journal of nutrition health & aging, Journal Year: 2022, Volume and Issue: 26(6), P. 637 - 651

Published: May 31, 2022

Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which associated with a myriad of adverse clinical outcomes. This paper, prepared by multidisciplinary expert working group from the Australian New Zealand Society for Frailty Research (ANZSSFR), provides an up-to-date overview current evidence recommendations based on narrative review literature screening, diagnosis, management sarcopenia patients within hospital setting. It also includes suggestions potential pathways to implement change encourage widespread adoption these evidence-informed settings. The concluded there was insufficient support any specific screening tool recommends assessment probable sarcopenia/sarcopenia using established criteria all (≥65 years) or younger (e.g., comorbidities) that may increase their risk sarcopenia. Diagnosis should be low muscle strength (grip five times sit-to-stand) diagnosis including mass quantified dual energy X-ray absorptiometry, bioelectrical impedance analysis absence diagnostic devices, calf circumference as proxy measure. Severe is represented addition impaired physical performance (slow gait speed). All investigated causes chronic/acute disease malnutrition), treated accordingly. For frailty, it recommended aged 70 years screened validated [Clinical Scale (CFS), Hospital Risk Score, FRAIL scale Index]. Patients positive undergo further Phenotype, Index information collected Comprehensive Geriatric Assessment (CGA). identified frail receive follow up health practitioner(s) individualized care plan. To treat sarcopenia, structured supervised multi-component exercise program incorporating elements resistance (muscle strengthening), challenging balance, functional mobility training prescribed early possible combined nutritional optimize protein intake correct deficiencies. There recommend pharmacological agents treatment frailty. Finally, facilitate integration into settings organization-wide approaches needed, Spread Sustain framework organizational culture change, help ‘champions’ drive changes. A team approach awareness education initiatives healthcare professionals ensure embedded sustained caregivers’ integrated pathway adherence

Language: Английский

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Cellular senescence and cardiovascular diseases: moving to the “heart” of the problem

Physiological Reviews, Journal Year: 2022, Volume and Issue: 103(1), P. 609 - 647

Published: Sept. 1, 2022

Cardiovascular diseases (CVDs) constitute the prime cause of global mortality, with an immense impact on patient quality life and disability. Clinical evidence has revealed a strong connection between cellular senescence worse cardiac outcomes in majority CVDs concerning both ischemic nonischemic cardiomyopathies. Cellular is characterized by cell cycle arrest accompanied alterations several metabolic pathways, resulting morphological functional changes. Metabolic rewiring senescent cells results marked paracrine activity, through unique secretome, often exerting deleterious effects neighboring cells. Here, we recapitulate hallmarks key molecular pathways involved context summarize different roles CVDs. In last few years, possibility eliminating various pathological conditions been increasingly explored, giving rise to field senotherapeutics. Therefore, additionally attempt clarify current state this focus discuss potential implementing senolytics as treatment option heart disease.

Language: Английский

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A coalition to heal—the impact of the cardiac microenvironment

Science, Journal Year: 2022, Volume and Issue: 377(6610)

Published: Sept. 1, 2022

Heart regenerative medicine has been gradually evolving from a view of the heart as nonregenerative organ with terminally differentiated cardiac muscle cells. Understanding biology during homeostasis and in response to injuries led realization that cellular communication between all cell types holds great promise for treatments. Indeed, recent studies highlight new disease-reversion concepts addition cardiomyocyte renewal, such matrix- vascular-targeted therapies, immunotherapy focus on inflammation fibrosis. In this review, we will discuss cross-talk within microenvironment how specific therapies aim target hostile milieu under pathological conditions.

Language: Английский

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Pharmacological clearance of senescent cells improves cardiac remodeling and function after myocardial infarction in female aged mice

Mechanisms of Ageing and Development, Journal Year: 2022, Volume and Issue: 208, P. 111740 - 111740

Published: Sept. 20, 2022

Language: Английский

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Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(17), P. 11454 - 11477

Published: Aug. 25, 2022

Neurodegenerative diseases (NDs) are currently incurable that cause progressive degeneration of nerve cells. Many the disease-causing proteins NDs "undruggable" for traditional small-molecule inhibitors (SMIs). None compounds attenuated amyloid-β (Aβ) accumulation process have entered clinical practice, and many phase III trials SMIs Alzheimer's disease (AD) failed. In recent years, emerging targeted protein degradation (TPD) technologies such as proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimaeras (LYTACs), autophagy-targeting (AUTACs) with TPD-assistive click-formed (CLIPTACs) deubiquitinase-targeting chimera (DUBTAC) developed rapidly. vitro in vivo experiments also confirmed TPD technology can target ND pathogenic proteins, bringing hope treatment NDs. Herein, we review latest technologies, introduce their targets technical characteristics, discuss potential research, providing a new perspective development field.

Language: Английский

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Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction

npj Aging, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 14, 2023

Abstract Myocardial infarction is a leading cause of morbidity and mortality. While reperfusion now standard therapy, pathological remodelling to heart failure remains clinical problem. Cellular senescence has been shown contribute disease pathophysiology treatment with the senolytic navitoclax attenuates inflammation, reduces adverse myocardial results in improved functional recovery. However, it unclear which senescent cell populations these processes. To identify whether cardiomyocytes post-myocardial infarction, we established transgenic model p16 (CDKN2A) expression was specifically knocked-out cardiomyocyte population. Following mice lacking demonstrated no difference hypertrophy but exhibited cardiac function significantly reduced scar size comparison control animals. This data demonstrates that participate remodelling. Importantly, inhibition led senescence-associated inflammation decreased markers within other lineages, consistent hypothesis promote by spreading cell-types. Collectively this study presents demonstration are major contributors dysfunction following infarction. Therefore, maximise potential for translation, important further understand mechanisms underlying how optimise strategies target lineage.

Language: Английский

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