Study investigates senescent phenotypes of human corneal endothelial cells upon UV-A exposure

Aging-USApr 30 2024

A new research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 8, entitled, "Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure."

In this new study, researchers Kohsaku Numa, Sandip Kumar Patel, Zhixin A. Zhang, Jordan B. Burton, Akifumi Matsumoto, Jun-Wei B. Hughes, Chie Sotozono, Birgit Schilling, Pierre-Yves Desprez, Judith Campisi (1948-2024), and Koji Kitazawa from Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine, University of Cambridge, and California Pacific Medical Center investigated the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A.

"We assessed cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation and expression of senescence markers (p16 and p21) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls."

The researchers performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs -; they also compared the results to non-senescent hCEnCs. Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-β-gal activity, decreased cell proliferation and elevated expression of p16 and p21. RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype.

"In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR."