Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102273 - 102273
Опубликована: Март 14, 2024
Язык: Английский
Aging Cell, Год журнала: 2023, Номер 22(2)
Опубликована: Янв. 13, 2023
Aging results in an elevated burden of senescent cells, senescence-associated secretory phenotype (SASP), and tissue infiltration immune cells contributing to chronic low-grade inflammation a host age-related diseases. Recent evidence suggests that the clearance alleviates its associated dysfunction However, effect this intervention on metabolic function old age remains poorly understood. Here, we demonstrate dasatinib quercetin (D&Q) have senolytic effects, reducing increase β-galactosidase, expression p16 p21 gene P16 protein perigonadal white adipose (pgWAT; all p ≤ 0.04). This treatment also suppressed subset pro-inflammatory SASP genes (mcp1, tnf-α, il-1α, il-1β, il-6, cxcl2, cxcl10), crown-like structures, abundance T macrophages pgWAT (all In liver skeletal muscle, did not find robust D&Q senescence inflammatory markers. Although observe difference glucose tolerance, improved fasting blood (p = 0.001) tolerance 0.007) mice was concomitant with lower hepatic gluconeogenesis. Additionally, insulin-stimulated suppression plasma NEFAs 0.01), reduced fed fasted triglycerides (both 0.04), systemic lipid 0.006). Collectively, from study suggest attenuates improves age. These findings implications for development therapeutic agents combat diseases
Язык: Английский
Процитировано
122
Nature Reviews Cardiology, Год журнала: 2023, Номер 20(11), С. 754 - 777
Опубликована: Май 16, 2023
Язык: Английский
Процитировано
115
Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(1), С. 1 - 12
Опубликована: Янв. 4, 2023
Abstract Senescence compromises the essential role that endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and development of age-related diseases. Their biological clinical significance calls for strategies identifying therapeutically targeting senescent cells. While senescence have been studied extensively, distinguishing what is distinctly remains a barrier to overcome an effective approach addressing it. Here, we review mechanisms underlying evidence its importance. Furthermore, discuss current state limitations approaches detection therapeutic intervention target cells, suggesting potential directions future research.
Язык: Английский
Процитировано
99
Nature Aging, Год журнала: 2024, Номер 4(1), С. 145 - 162
Опубликована: Янв. 10, 2024
Abstract Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds declines oocyte quality. Despite growing body work, the field lacks comprehensive cellular map transcriptomic changes mouse ovary identify early drivers ovarian decline. To fill this gap we performed single-cell RNA sequencing on tissue from young (3-month-old) reproductively aged (9-month-old) mice. Our analysis revealed doubling immune cells ovary, with lymphocyte proportions increasing most, was confirmed by flow cytometry. We also found an age-related downregulation collagenase pathways stromal fibroblasts, rises fibrosis. Follicular displayed stress-response, immunogenic fibrotic pathway inductions aging. This report provides critical insights into mechanisms responsible for phenotypes. The data can be explored interactively via Shiny-based web application.
Язык: Английский
Процитировано
57
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
Процитировано
49
Archives of Toxicology, Год журнала: 2023, Номер 97(5), С. 1195 - 1245
Опубликована: Март 22, 2023
Язык: Английский
Процитировано
46
Antioxidants, Год журнала: 2023, Номер 12(2), С. 258 - 258
Опубликована: Янв. 23, 2023
Quercetin is a monomeric polyphenol of plant origin that belongs to the flavonol-type flavonoid subclass. Extensive studies using cultured cells and experimental model animals have demonstrated anti-atherosclerotic effects dietary quercetin in relation prevention cardiovascular disease (CVD). As exclusively present plant-based foods form glycosides, this review focuses on bioavailability bioefficacy glycosides vascular health effects. Some glucose-bound are absorbed from small intestine after glucuronide/sulfate conjugation. Both conjugated metabolites deconjugated aglycones formed by plasma β-glucuronidase activity act as food-derived anti-atherogenic factors exerting antioxidant, anti-inflammatory, low-density lipoprotein cholesterol-lowering However, most reach large intestine, where they subject gut microbiota-dependent catabolism resulting deglycosylated aglycone chain-scission products. These catabolites also affect transfer into circulation. Furthermore, may improve microbiota profiles. A variety human cohort intervention support idea intake glycoside-rich such onion helps prevent CVD. Thus, offer potential benefits terms possible clinical applications.
Язык: Английский
Процитировано
43
Cells, Год журнала: 2023, Номер 12(12), С. 1640 - 1640
Опубликована: Июнь 15, 2023
The physiological functions of endothelial cells control vascular tone, permeability, inflammation, and angiogenesis, which significantly help to maintain a healthy system. Several cardiovascular diseases are characterized by cell activation or dysfunction triggered external stimuli such as disturbed flow, hypoxia, growth factors, cytokines in response high levels low-density lipoprotein cholesterol, hypertension, diabetes, aging, drugs, smoking. Increasing evidence suggests that uncontrolled proinflammatory signaling further alteration phenotypes barrier disruption, increased mesenchymal transition (EndMT), metabolic reprogramming induce diseases, multiple studies focusing on finding the pathways mechanisms involved it. This review highlights main their effects function. In order provide rational direction for future research, we also compiled most recent data regarding impact potential targets impede pathogenic process.
Язык: Английский
Процитировано
43
Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102294 - 102294
Опубликована: Апрель 5, 2024
Язык: Английский
Процитировано
33
Advanced Materials, Год журнала: 2024, Номер 36(26)
Опубликована: Апрель 7, 2024
Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.
Язык: Английский
Процитировано
27