» Articles » PMID: 37880106

Potential Clinical Implications of Senotherapies for Cardiovascular Disease

Overview
Journal Circ J
Date 2023 Oct 25
PMID 37880106
Authors
Affiliations
Soon will be listed here.
Abstract

Aging is a major risk factor for cardiovascular diseases (CVDs) and accumulating evidence indicates that biological aging has a significant effect on the onset and progression of CVDs. In recent years, therapies targeting senescent cells (senotherapies), particularly senolytics that selectively eliminate senescent cells, have been developed and show promise for treating geriatric syndromes and age-associated diseases, including CVDs. In 2 pilot studies published in 2019 the senolytic combination, dasatinib plus quercetin, improved physical function in patients with idiopathic pulmonary fibrosis and eliminated senescent cells from adipose tissue in patients with diabetic kidney disease. More than 30 clinical trials using senolytics are currently underway or planned. In preclinical CVD models, senolytics appear to improve heart failure, ischemic heart disease, valvular heart disease, atherosclerosis, aortic aneurysm, vascular dysfunction, dialysis arteriovenous fistula patency, and pre-eclampsia. Because senotherapies are completely different strategies from existing treatment paradigms, they might alleviate diseases for which there are no current effective treatments or they could be used in addition to current therapies to enhance efficacy. Moreover, senotherapies might delay, prevent, alleviate or treat multiple diseases in the elderly and reduce polypharmacy, because senotherapies target fundamental aging mechanisms. We comprehensively summarize the preclinical evidence about senotherapies for CVDs and discuss future prospects for their clinical application.

Citing Articles

Roadmap for alleviating the manifestations of ageing in the cardiovascular system.

Liberale L, Tual-Chalot S, Sedej S, Ministrini S, Georgiopoulos G, Grunewald M Nat Rev Cardiol. 2025; .

PMID: 39972009 DOI: 10.1038/s41569-025-01130-5.


The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.

Burdusel D, Doeppner T, Surugiu R, Hermann D, Olaru D, Popa-Wagner A Biomolecules. 2025; 15(1).

PMID: 39858413 PMC: 11762397. DOI: 10.3390/biom15010018.


A Dual Role of the Senescence Marker P16Ink4a in Liver Endothelial Cell Function.

Wagner K, Safwan-Zaiter H, Wagner N Cells. 2024; 13(23).

PMID: 39682678 PMC: 11640762. DOI: 10.3390/cells13231929.


Senescent cell depletion alleviates obesity-related metabolic and cardiac disorders.

de Oliveira Silva T, Lunardon G, Lino C, de Almeida Silva A, Zhang S, Irigoyen M Mol Metab. 2024; 91():102065.

PMID: 39557194 PMC: 11636344. DOI: 10.1016/j.molmet.2024.102065.


Cardiovascular aging: spotlight on mitochondria.

Ali M, Gioscia-Ryan R, Yang D, Sutton N, Tyrrell D Am J Physiol Heart Circ Physiol. 2023; 326(2):H317-H333.

PMID: 38038719 PMC: 11219063. DOI: 10.1152/ajpheart.00632.2023.

References
1.
Xie J, Chen Y, Hu C, Pan Q, Wang B, Li X . Premature senescence of cardiac fibroblasts and atrial fibrosis in patients with atrial fibrillation. Oncotarget. 2017; 8(35):57981-57990. PMC: 5601627. DOI: 10.18632/oncotarget.19853. View

2.
Lakshminarayan K, Solid C, Collins A, Anderson D, Herzog C . Atrial fibrillation and stroke in the general medicare population: a 10-year perspective (1992 to 2002). Stroke. 2006; 37(8):1969-74. DOI: 10.1161/01.STR.0000230607.07928.17. View

3.
Panchal S, Poudyal H, Brown L . Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. J Nutr. 2012; 142(6):1026-32. DOI: 10.3945/jn.111.157263. View

4.
Triana-Martinez F, Picallos-Rabina P, Da Silva-Alvarez S, Pietrocola F, Llanos S, Rodilla V . Identification and characterization of Cardiac Glycosides as senolytic compounds. Nat Commun. 2019; 10(1):4731. PMC: 6803708. DOI: 10.1038/s41467-019-12888-x. View

5.
Childs B, Baker D, Wijshake T, Conover C, Campisi J, van Deursen J . Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016; 354(6311):472-477. PMC: 5112585. DOI: 10.1126/science.aaf6659. View