image: Figure 2. PTGS2 induces and maintains NHEK senescence. (A) NHEKs (donor 4F0315) were treated with NS398 at 5 or 10 µM or DMSO every 48 h. Left panel: During the treatment, cells were passaged when reaching 70% confluence, counted, and the number of population doublings was calculated (see Methods). The experiment was performed in triplicate, each point representing the mean of three counts. Significant differences between DMSO control and 5 or 10 µM NS398 treatment are indicated. Right panel: Senescent NHEKs were treated as in (A), then, a SA-β-Gal assay was performed seven days post-treatments. (B) Senescent NHEKs (donor K23FC1) were transfected with a pool of 4 siRNAs targeting PTGS2, or with non-target siRNAs. Left panel: Evaluation of the efficacy of the siRNAs by Western Blot. GAPDH was used as a loading control. Right panel: Four days after transfection, a SA-β-Gal assay was performed. The bars represent the mean ±SD of three counts of blue cells (**p < 0.01). (C) Senescent NHEKs (donor K23FC1) were treated with NS398 or rofecoxib at the indicated concentrations for four days. Then, a SA-β-Gal assay was performed. The bars represent the mean ±SD of three counts of blue cells (*p < 0.05; **p < 0.01). (D) ELISA assays for measuring the amounts of GM-CSF and G-CSF in the conditioned media (secreted) of exponentially growing, pre-senescent and senescent NHEKs (donor K40FH1) treated or not with NS398 (5 µM) for 16 hrs. Measures were performed in triplicate. The bars represent the mean ± SD of three counts. Significant differences are indicated with asterisks with *p < 0.05; **p < 0.01; ***p < 0.001.
Credit: © 2024 Srour et al.
“Our data indicate that the PTGS2 level and the production of PGE2 are increased during in vitro senescence of NHEKs, as well as during aging of skin epidermal keratinocytes.”
BUFFALO, NY- December 10, 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 21 on November 18, 2024, entitled, “Prostaglandin E2 regulates senescence and post-senescence neoplastic escape in primary human keratinocytes.”
Researchers Elise Srour, Nathalie Martin, Claire Drullion, Clémentine De Schutter, Joëlle Giroud, Adrien Pioger, Julie Deslé, Laure Saas, Joe Nassour, Julien Théry, Gauthier Decanter, Nicolas Penel, Chantal Vercamer, Clara Salazar-Cardozo, Corinne Abbadie, and Olivier Pluquet from CNRS, University of Lille, the Oscar Lambret Center, and the University of Colorado School of Medicine have revealed how a molecule called Prostaglandin E2 (PGE2) influences skin aging and cancer risk.
Their study shows that PGE2 not only drives skin cells to age but also enables some of these aging cells to bypass natural limits and develop into pre-cancerous cells. This process provides insights into why older skin is more susceptible to cancer.
The study focused on keratinocytes, the primary cells in the outer layer of the skin. As these cells age, they enter a state called senescence, where they stop dividing to prevent damaged cells from turning cancerous. While this process typically serves as a protective mechanism, the researchers found that, in certain cases, some senescent cells can escape this state, re-enter the cell cycle, and acquire characteristics of early cancer. By examining keratinocytes from donors of different ethnicities and ages, the researchers identified the PTGS2/PGE2/EP4 pathway as a key driver of this escape process.
The researchers show that blocking PGE2 or its associated pathway reduced the chances of aged cells becoming precancerous. This suggests that drugs targeting this pathway, including some anti-inflammatory medications already in use, might be repurposed to slow skin aging and prevent early-stage skin cancers. Additionally, the study also found that PGE2 levels increase in the skin as it ages, further supporting its role in skin health and disease.
“These results indicate that the PTGS2/PGE2/EP4 pathway is required to induce and maintain the senescent phenotype of NHEKs, and that PGE2 level is a potential determinant of the initial steps of the age-related oncogenic process.”
The team also highlighted the broader implications of their work. The PTGS2/PGE2/EP4 pathway is not only linked to skin health but also to age-related inflammation, a condition that contributes to several diseases. By addressing this pathway, researchers hope to address not only skin aging but other health challenges linked to aging and chronic inflammation.
In conclusion, this study reveals important molecular drivers of skin aging and early cancer, leading the way for new approaches that can promote healthier skin.
Read the full paper: DOI: https://doi.org/10.18632/aging.206149
Corresponding author: Olivier Pluquet – olivier.pluquet@ibl.cnrs.fr
Video short: https://www.youtube.com/watch?v=4aNf3X2RJSw
Keywords: aging, PTGS2, prostaglandins, EP receptors, senescence, neoplastic transformation, keratinocyte
Click here to sign up for free Altmetric alerts about this article.
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 Central, Web 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).
Please visit our website at www.Aging-US.com and connect with us:
- X
- YouTube
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging publication updates.
For media inquiries, please contact media@impactjournals.com.
Aging (Aging-US) Journal Office
6666 E. Quaker St., Suite 1
Orchard Park, NY 14127
Phone: 1-800-922-0957, option 1
Journal
Aging-US
Method of Research
News article
Subject of Research
Not applicable
Article Title
Prostaglandin E2 regulates senescence and post-senescence neoplastic escape in primary human keratinocytes
Article Publication Date
18-Nov-2024
COI Statement
The authors declare no conflicts of interest related to this study.