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Senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in mice

“This study represents one of the first to evaluate the impact of senolytic agents D+Q on the clinical development of pelvic organ prolapse and expression of proteins associated with cellular senescence in a mouse model.”

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Impact Journals LLC

Use of the senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in a mouse animal model

image: 

Figure 1. Impact of serial dasatinib and quercetin (D+Q) injections on development of pelvic organ prolapse in wild type (WT) and Fibulin-5 knockout (Fbln-5-/-) mice. D+Q or placebo injections were administered at weeks 4, 5, 6, 7 and 8 of life to treatment and control groups, respectively. Mouse pelvic organ prolapse quantification measurements were used to obtain weekly perineal body length (A) and vaginal bulge height (B) values. WT control (n=27), WT treatment (n=27), Fbln-5-/- control (n=33), Fbln-5-/- treatment (n=30). p <0.05 between Fbln-5-/- treatment mice and Fbln-5-/- control mice, and between Fbln-5-/- treatment mice and WT treatment mice (A).

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Credit: 2024 Tappy et al.

“This study represents one of the first to evaluate the impact of senolytic agents D+Q on the clinical development of pelvic organ prolapse and expression of proteins associated with cellular senescence in a mouse model.”

BUFFALO, NY- October 22, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science), Volume 16, Issue 19 on September 26, 2024, entitled, “Use of the senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in a mouse animal model.”

Pelvic organ prolapse is a common condition among women in the U.S., with a 13% estimated risk of requiring surgery by age 80. Senolytic agents like dasatinib and quercetin (D+Q) target age-related cellular senescence and reduce senescent cell activity in various disease processes.

In their paper, researchers Erryn Tappy, Haolin Shi, Jessica Pruszynski, and Maria Florian-Rodriguez from the University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology in Dallas, utilized a mouse model of pelvic organ prolapse, Fibulin-5 knockout (Fbln-5-/-) mice, to assess the ability of D+Q to prevent development of prolapse.

The D+Q injections administered did not result in significant differences in prolapse development but did reduce cellular senescence markers in Fbln-5-/- mice. This suggests senolytic agents may help mitigate the role of cellular senescence in tissue dysfunction associated with prolapse. The researchers suggest that further studies are needed to determine optimal timing, dosage, and delivery of senolytics for prolapse prevention.

"This study represents one of the first to evaluate the impact of senolytic agents D+Q on the clinical development of pelvic organ prolapse and expression of proteins associated with cellular senescence in a mouse model.”

Continue reading: DOI: https://doi.org/10.18632/aging.206120

Corresponding Author: Maria Florian-Rodriguez - Maria.Florian-Rodriguez@UTSouthwestern.edu

Keywords: aging, pelvic organ prolapse, cellular senescence, senolytic agents, animal model

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About Aging:

The journal Aging aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed CentralWeb of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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