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

• Published in: International journal of molecular sciences Vol. 25; no. 15; p. 8153
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: Acids; Aging; Antioxidants - pharmacology; Cell cycle; Cells, Cultured; Cellular Senescence - drug effects; Coumaric Acids - pharmacology; DNA damage; DNA Damage - drug effects; DNA repair; Homeostasis; Humans; Hydrogen Peroxide - metabolism; Inflammation; Inflammation - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Keratinocytes - drug effects; Keratinocytes - metabolism; Metabolism; Metabolites; Oxidative stress; Oxidative Stress - drug effects; para-coumaric acid; para-hydroxycinnamic acid; Polyphenols; Proteins; Radiation; Senescence; Skin; Skin - drug effects; Skin - metabolism; Skin Aging - drug effects; Tea; Ultraviolet Rays - adverse effects; senescence; para-hydroxycinnamic acid; inflammaging; inflammation; keratinocyte; para-coumaric acid; DNA damage; aging; DNA repair; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158153

-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 H O 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 PGE , 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.