Fisetin extends lifespan in a murine model of recessive dystrophic epidermolysis bullosa

Miller, W. C., Strege, C. L., Popp, C. M., Tito, S. M. I., Eide, C., Ebens, C. L., Riddle, M., Lees, C., Seelig, D., Bui, K., Yousefzadeh, M. J., McGrath, J., Tolar, J.

University of Minnesota Medical School Twin CitiesUniversity of Minnesota Medical School Twin Cities · biorxiv

Paper

Abstract

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare genodermatosis characterized clinically by extensive inflammation, cutaneous destruction, and fibrosis that demonstrates properties similar to rapid skin aging. As tissue ages, it accumulates cellular damage and exhaustion leading to a state of senescence. Cellular senescence is an aging or disease-related phenomenon of stable exit from the cell cycle that leads to an increased inflammatory phenotype. RDEB and other EB subsets of patients need an adjunct to or alternate therapy that addresses the issues of inflammation, pain, and pruritus. Fisetin is a safe, naturally occurring compound proven to be effective at sensitizing senescent cells to cell death and ameliorating senescence-associated inflammation. In this paper, we demonstrate fisetins ability to increase survival and reduce senescent cell burden in a hypomorphic mouse model of RDEB.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper addresses a specific genetic condition related to skin aging and inflammation, which aligns with the broader themes of cellular senescence and its implications for aging. However, while it presents findings on fisetin's effects on lifespan and senescent cell burden in a mouse model, the focus remains on a specific disease rather than a comprehensive approach to understanding or mitigating the root causes of aging. Thus, while it contributes to the field, its impact is limited and more incremental than transformative.

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