1. Para -Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.
- Author
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Tan CYR, Morenc M, Setiawan M, Lim ZZY, Soon AL, Bierman JC, Vires L, Laughlin T, DeAngelis YM, Rovito H, Jarrold BB, Nguyen TQN, Lim JSY, Kent O, Määttä A, Benham AM, Hawkins TJ, Lee XE, Ehrman MC, Oblong JE, Dreesen O, and Bellanger S
- Subjects
- Humans, Inflammation metabolism, DNA Damage drug effects, Hydrogen Peroxide metabolism, Ultraviolet Rays adverse effects, Antioxidants pharmacology, Cells, Cultured, Interleukin-8 metabolism, Interleukin-6 metabolism, Coumaric Acids pharmacology, Cellular Senescence drug effects, Keratinocytes drug effects, Keratinocytes metabolism, Oxidative Stress drug effects, Skin metabolism, Skin drug effects, Skin Aging drug effects
- 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 H
2 O2 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.- Published
- 2024
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