Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age

Aging Cell, Journal Year: 2023, Volume and Issue: 22(2)

Published: Jan. 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

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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Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(1), P. 1 - 12

Published: Jan. 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.

Language: Английский

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A single-cell atlas of the aging mouse ovary

Nature Aging, Journal Year: 2024, Volume and Issue: 4(1), P. 145 - 162

Published: Jan. 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.

Language: Английский

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Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1296 - 1296

Published: May 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

Language: Английский

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A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS)

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(5), P. 1195 - 1245

Published: March 22, 2023

Language: Английский

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Potential Role of Quercetin Glycosides as Anti-Atherosclerotic Food-Derived Factors for Human Health

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 258 - 258

Published: Jan. 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.

Language: Английский

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Vascular Inflammatory Diseases and Endothelial Phenotypes

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1640 - 1640

Published: June 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.

Language: Английский

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Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102294 - 102294

Published: April 5, 2024

Language: Английский

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Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: April 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.

Language: Английский

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