Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models

Tan, Christina Yan Ru; Morenc, Malgorzata; Setiawan, Melina; Lim, Zen Zhi Yan; Soon, Ai Ling; Bierman, John C.; Vires, Laura; Laughlin, Timothy; DeAngelis, Yvonne M.; Rovito, Holly; Jarrold, Bradley B.; Nguyen, Thi Quynh Ngoc; Lim, John Soon Yew; Kent, Olivia; Määttä, Arto; Benham, Adam M.; Hawkins, Timothy J.; Lee, Xin Er; Ehrman, Matthew C.; Oblong, John E.; Dreesen, Oliver; Bellanger, Sophie

Abstract

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Citation

Tan, C. Y. R., Morenc, M., Setiawan, M., Lim, Z. Z. Y., Soon, A. L., Bierman, J. C., Vires, L., Laughlin, T., DeAngelis, Y. M., Rovito, H., Jarrold, B. B., Nguyen, T. Q. N., Lim, J. S. Y., Kent, O., Määttä, A., Benham, A. M., Hawkins, T. J., Lee, X. E., Ehrman, M. C., Oblong, J. E., …Bellanger, S. (2024). Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models. International Journal of Molecular Sciences, 25(15), Article 8153. https://doi.org/10.3390/ijms25158153

• Journal Article Type: Article
• Acceptance Date: Jul 22, 2024
• Online Publication Date: Jul 26, 2024
• Publication Date: Jul 26, 2024
• Deposit Date: Aug 14, 2024
• Publicly Available Date: Aug 14, 2024
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 15
• Article Number: 8153
• DOI: https://doi.org/10.3390/ijms25158153
• Keywords: DNA damage, senescence, keratinocyte, DNA repair, para-coumaric acid, aging, inflammaging, inflammation, para-hydroxycinnamic acid, oxidative stress
• Public URL: https://durham-repository.worktribe.com/output/2751438