Quercetin and dasatinib, two powerful senolytics in age-related cardiovascular disease

Nieto, Mario; Konigsberg, Mina; Silva-Palacios, Alejandro

doi:10.1007/s10522-023-10068-5

Cited by 5 publications

(4 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that the senolytic combination DQ ameliorated the androgen-induced increases in the expression of cellular senescence markers and the SASP-related factor IL-6 in GCs in vitro and in vivo . Dasatinib, which is used for the treatment of chronic myeloid leukemia, is an inhibitor of several receptor tyrosine kinases ( Montero et al , 2011 ; Nieto et al , 2023 ). Regarding its senolytic potential, dasatinib reduces the number of senescent preadipocytes following exposure to ionizing radiation ( Zhu et al , 2015 ) and reduces the cardiac expression of p16 in a mouse model of type 2 diabetes mellitus ( Gu et al , 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome

Tanaka,

Urata,

Harada

et al. 2024

Molecular Human Reproduction

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed ‘senescence-associated secretory phenotype’ (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated β-galactosidase (SA-β-gal); and the SASP-related factor interleukin (IL)-6; were significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.

show abstract

Section: Discussionmentioning

confidence: 99%

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome

Tanaka,

Urata,

Harada

et al. 2024

Molecular Human Reproduction

View full text Add to dashboard Cite

show abstract

“…Therefore, the effectiveness of Nintedanib in treating CHF can be further verified in the future in combination with large samples clinical study or animal experiments. Dasatinib combined with quercetin can effectively eliminate senescent cells in myocardial tissue, can alleviate the progression of myocardial injury, and can be used for age-related cardiac pathology 34 . In summary, candidate drugs such as Midostaurin, Nintedanib, and Dasatinib screened out through drug repurposing of disease modules can be verified for their effectiveness against CHF through animal experiments or clinical research in the future.…”

Section: Discussionmentioning

confidence: 99%

Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective

Xie,

Zhang,

Zhu

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Chronic Heart Failure (CHF) is a significant global public health issue, with high mortality and morbidity rates and associated costs. Disease modules, which are collections of disease-related genes, offer an effective approach to understanding diseases from a biological network perspective. We employed the multi-Steiner tree algorithm within the NeDRex platform to extract CHF disease modules, and subsequently utilized the Trustrank algorithm to rank potential drugs for repurposing. The constructed disease module was then used to investigate the mechanism by which Panax ginseng ameliorates CHF. The active constituents of Panax ginseng were identified through a comprehensive review of the TCMSP database and relevant literature. The Swiss target prediction database was utilized to determine the action targets of these components. These targets were then cross-referenced with the CHF disease module in the STRING database to establish protein–protein interaction (PPI) relationships. Potential action pathways were uncovered through Gene Ontology (GO) and KEGG pathway enrichment analyses on the DAVID platform. Molecular docking, the determination of the interaction of biological macromolecules with their ligands, and visualization were conducted using Autodock Vina, PLIP, and PyMOL, respectively. The findings suggest that drugs such as dasatinib and mitoxantrone, which have low docking scores with key disease proteins and are reported in the literature as effective against CHF, could be promising. Key components of Panax ginseng, including ginsenoside rh4 and ginsenoside rg5, may exert their effects by targeting key proteins such as AKT1, TNF, NFKB1, among others, thereby influencing the PI3K-Akt and calcium signaling pathways. In conclusion, drugs like dasatinib and midostaurin may be suitable for CHF treatment, and Panax ginseng could potentially mitigate the progression of CHF through a multi-component-multi-target-multi-pathway approach. Disease module analysis emerges as an effective strategy for exploring drug repurposing and the mechanisms of traditional Chinese medicine in disease treatment.

show abstract

“…In this context, Cycloastraganol represents the only discovered telomerase activator so far, being able to delay telomere shortening by inducing telomerase expression [169]. Senolytics, designed to identify and target senescent cells, include common drugs like dasatinib and quercetin [170,171]. Bcl-2 inhibitory drugs UBX1325 and UBX1967, treating AMD, promote apoptosis in senescent cells [172].…”

Section: Sirt Activators Telomerase Enhancers and Senolyticsmentioning

confidence: 99%

Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress

Cui,

Buonfiglio,

Pfeiffer

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Acknowledged as a significant pathogenetic driver for numerous diseases, aging has become a focal point in addressing the profound changes associated with increasing human life expectancy, posing a critical concern for global public health. Emerging evidence suggests that factors influencing vascular aging extend their impact to choroidal and retinal blood vessels. The objective of this work is to provide a comprehensive overview of the impact of vascular aging on ocular blood vessels and related diseases. Additionally, this study aims to illuminate molecular insights contributing to vascular cell aging, with a particular emphasis on the choroid and retina. Moreover, innovative molecular targets operating within the domain of ocular vascular aging are presented and discussed.

show abstract

Quercetin and dasatinib, two powerful senolytics in age-related cardiovascular disease

Cited by 5 publications

References 73 publications

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome

Exploring the pathways of drug repurposing and Panax ginseng treatment mechanisms in chronic heart failure: a disease module analysis perspective

Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress

Contact Info

Product

Resources

About