Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions

Frontiers in Pharmacology
Marie Helena DochertyDavid A Ferenbach

Abstract

Cellular senescence refers to a cellular phenotype characterized by an altered transcriptome, pro-inflammatory secretome, and generally irreversible growth arrest. Acutely senescent cells are widely recognized as performing key physiological functions in vivo promoting normal organogenesis, successful wound repair, and cancer defense. In contrast, the accumulation of chronically senescent cells in response to aging, cell stress, genotoxic damage, and other injurious stimuli is increasingly recognized as an important contributor to organ dysfunction, tissue fibrosis, and the more generalized aging phenotype. In this review, we summarize our current knowledge of the role of senescent cells in promoting progressive fibrosis and dysfunction with a particular focus on the kidney and reference to other organ systems. Specific differences between healthy and senescent cells are reviewed along with a summary of several experimental pharmacological approaches to deplete or manipulate senescent cells to preserve organ integrity and function with aging and after injury. Finally, key questions for future research and clinical translation are discussed.

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Citations

Nov 11, 2020·Cells·Yohan SantinAngelo Parini
Apr 4, 2021·Biomolecules·Oscar Salvador Barrera-VázquezGil Alfonso Magos-Guerrero
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Aug 13, 2021·Frontiers in Pharmacology·Rohan Samarakoon, Paul J Higgins
Dec 1, 2021·Plastic and Reconstructive Surgery·Ben P Lee, Lorna W Harries

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Methods Mentioned

BETA
transgenic
biopsies
biopsy
transmission electron microscopy

Clinical Trials Mentioned

NCT02848131
NCT04063124
NCT04313634
NCT02915198
NCT03451006
NCT04129944

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