Regression of cardiac hypertrophy in health and disease: mechanisms and therapeutic potential

Nature Reviews Cardiology, Год журнала: 2023, Номер 20(5), С. 347 - 363

Опубликована: Янв. 4, 2023

Язык: Английский

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Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Cells, Год журнала: 2023, Номер 12(9), С. 1296 - 1296

Опубликована: Май 2, 2023

Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many Therapies targeting senescent cells, especially senolytic drugs selectively induce removal, have shown to delay, prevent, alleviate, treat multiple preclinical models. Some clinical trials already completed are underway for a number of geriatric syndromes. Understanding how cellular senescence affects the various types system, such as endothelial vascular smooth muscle fibroblasts, immune progenitor cardiomyocytes, is important facilitate translation senotherapeutics into interventions. This review highlights: (1) characteristics their involvement diseases, focusing on aforementioned types, (2) evidence about other senotherapeutics, (3) future path potential

Язык: Английский

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The role of the immunosuppressive PD-1/PD-L1 checkpoint pathway in the aging process and age-related diseases

Journal of Molecular Medicine, Год журнала: 2024, Номер 102(6), С. 733 - 750

Опубликована: Апрель 11, 2024

Abstract The accumulation of senescent cells within tissues is a hallmark the aging process. Senescent are also commonly present in many age-related diseases and cancer microenvironment. escape abnormal from immune surveillance indicates that there some defect function cytotoxic cells, e.g., CD8 + T natural killer (NK) cells. Recent studies have revealed expression programmed death-ligand 1 (PD-L1) protein abundantly increased An increase amount PD-L1 protects clearance by PD-1 checkpoint receptor In fact, activation suppresses properties NK promoting state immunosenescence. inhibitory PD-1/PD-L1 pathway acts cooperation with immunosuppressive cells; for example, can enhance differentiation regulatory (Treg), myeloid-derived suppressor (MDSC), M2 macrophages, whereas cytokines secreted stimulate protein. Interestingly, signaling pathways known to promote cellular senescence process crucial stimulators protein, epigenetic regulation, inflammatory mediators, mTOR-related signaling, cGAS-STING pathway, AhR signaling. It seems axis has role thus it promotes tissues. Thus, blockade might be potential anti-aging senolytic therapy. Key messages accumulate during diseases. able Expression markedly increases Age-related stimulates Inhibitory

Язык: Английский

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

Physiological Reviews, Год журнала: 2022, Номер 103(1), С. 609 - 647

Опубликована: Сен. 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.

Язык: Английский

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Innate Immunity System in Patients With Cardiovascular and Kidney Disease

Circulation Research, Год журнала: 2023, Номер 132(8), С. 915 - 932

Опубликована: Апрель 13, 2023

With a global burden of 844 million, chronic kidney disease (CKD) is now considered public health priority. Cardiovascular risk pervasive in this population, and low-grade systemic inflammation an established driver adverse cardiovascular outcomes these patients. Accelerated cellular senescence, gut microbiota-dependent immune activation, posttranslational lipoprotein modifications, neuroimmune interactions, osmotic nonosmotic sodium accumulation, acute injury, precipitation crystals the vascular system all concur determining unique severity CKD. Cohort studies documented strong link between various biomarkers progression to failure events patients with Interventions targeting diverse steps innate response may reduce disease. Among these, inhibition IL-1β (interleukin-1 beta) signaling by canakinumab reduced for coronary heart disease, protection was equally without Several old (colchicine) new drugs system, like IL-6 (interleukin 6) antagonist ziltivekimab, are being tested large randomized clinical trials thoroughly test hypothesis that mitigating translate into better

Язык: Английский

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Focus on senescence: Clinical significance and practical applications

Journal of Internal Medicine, Год журнала: 2024, Номер 295(5), С. 599 - 619

Опубликована: Март 6, 2024

Abstract The older population is increasing worldwide, and life expectancy continuously rising, predominantly thanks to medical technological progress. Healthspan refers the number of years an individual can live in good health. From a gerontological viewpoint, mission extend spent health, promoting well‐being minimizing impact aging‐related diseases slow aging process. Biologically, malleable process characterized by intra‐ inter‐individual heterogeneous dynamic balance between accumulating damage repair mechanisms. Cellular senescence key component this process, with senescent cells different tissues organs, leading age‐related disease susceptibility over time. Removing from body or slowing down burden rate has been proposed as efficient way reduce age‐dependent deterioration. In animal models, senotherapeutic molecules lifespan either senolytic senomorphic activity. Much research shows that dietary physical activity‐driven lifestyle interventions protect against senescence. This narrative review aims summarize current knowledge on targeting risk models their translational potential for humans. We focused studies have examined role senotherapeutics modifying burdens. concludes general discussion mechanisms underlying unique trajectory its implications future research.

Язык: Английский

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Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

Aging and Disease, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Cellular senescence is characterized by the permanent arrest of cell proliferation and a response to endogenous exogenous stress. The continuous accumulation senescent cells (SnCs) in body leads development aging age-related diseases (such as neurodegenerative diseases, cancer, metabolic cardiovascular osteoarthritis). In face growing challenge several compounds have received widespread attention for their potential target SnCs. As result, senolytics (compounds that selectively eliminate SnCs) senomorphics alter intercellular communication modulate behavior become hot research topics field anti-aging. addition, strategies such combination therapies immune-based approaches also made significant progress anti-aging therapy. this article, we discuss latest on targeting SnCs gain deeper understanding mechanism action impact different with aim providing more effective references therapeutic ideas clinical treatment ever-grave challenges diseases.

Язык: Английский

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Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3319 - 3319

Опубликована: Март 14, 2024

The population of cancer survivors has markedly increased due to the rapid improvements in treatment. However, experience accelerated aging, which leads chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after diagnosis Cellular senescence, a hallmark is one mechanisms that contribute aging survivors. Several measures, including measures based on clinical markers biomarkers, have been proposed estimate process, some them shown associations with mortality frailty anti-aging interventions, lifestyle changes drugs, proposed. Future research, particularly large-scale studies, needed determine efficiency these interventions before considering their application clinics. This review focuses cellular senescence survivors, assessment process using high prevalence population, well possible opportunities for interventions. A deeper understanding will development effective strategies mitigate improve quality life.

Язык: Английский

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Action and therapeutic targets of myosin light chain kinase, an important cardiovascular signaling mechanism

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107276 - 107276

Опубликована: Июнь 27, 2024

The global incidence of cardiac diseases is increasing, imposing a substantial socioeconomic burden on healthcare systems. pathogenesis cardiovascular disease complex and not fully understood, the physiological function heart inextricably linked to well-regulated muscle movement. Myosin light chain kinase (MLCK) essential for myocardial contraction diastole, electrophysiological homeostasis, vasoconstriction vascular nerves blood pressure regulation. In this sense, MLCK appears be an attractive therapeutic target diseases. participates in cell movement migration through diverse pathways, including regulation calcium activation myosin phosphorylation, stimulation smooth or relaxation. Recently, phosphorylation chains has been shown closely associated with exercise signaling, mediates systolic diastolic functions interaction thick filaments actin thin filaments. It works by upholding integrity cytoskeleton, modifying conformation head, modulating innervation. governs adrenergic sympathetic nervous systems, extracellular transport, endothelial permeability, nitric oxide angiotensin II. Additionally, plays crucial role process aging. Multiple natural products/phytochemicals chemical compounds, such as quercetin, cyclosporin, ML-7 hydrochloride, have regulate cardiomyocyte MLCK. MLCK-modifying capacity these compounds should considered designing novel agents. This review summarizes mechanism action system potential reported processes.

Язык: Английский

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Senescent cardiac fibroblasts: A key role in cardiac fibrosis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1869(4), С. 166642 - 166642

Опубликована: Янв. 18, 2023

Язык: Английский

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