Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications
Open accessAbstract
Ambient air particulate matter (PM) induces senescence in human skin cells. However, the underlying mechanisms remain largely unknown. We investigated how epigenetic regulatory mechanisms participate in cellular senescence induced by PM with a diameter <2.5 (PM 2.5) in human keratinocytes and mouse skin tissues. PM 2.5-treated cells exhibited characteristics of cellular senescence. PM 2.5 induced a decrease in DNA methyltransferase (DNMT) expression and an increase in DNA demethylase (ten–eleven translocation; TET) expression, leading to hypomethylation of the p16INK4A promoter region. In addition, PM 2.5 led to a decrease in polycomb EZH2 histone methyltransferase expression, whereas the expression of the epigenetic transcriptional activator MLL1 increased. Furthermore, binding of DNMT1, DNMT3B, and EZH2 to the promoter region of p16INK4A decreased in PM 2.5-treated keratinocytes, whereas TET1 and MLL1 binding increased, leading to decreased histone H3 lysine 27 trimethylation (H3K27Me3) and increased H3K4Me3 in the promoter of p16INK4A. PM 2.5-induced senescence involved aryl hydrocarbon receptor (AhR)-induced reactive oxygen species (ROS) production. ROS scavenging dampened PM 2.5-induced cellular senescence through regulation of DNA and histone methylation. Altogether, our work shows that skin senescence induced by environmental PM 2.5 occurs through ROS-dependent the epigenetic modification of senescence-associated gene expression. Our findings provide information for the design of preventive and therapeutic strategies against skin senescence, particularly in light of the increasing problem of PM 2.5 exposure due to air pollution.
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PM2.5 induces cellular senescence in a ROS-dependent manner.
“A previous study has also shown that PM2.5 induces cellular senescence in a ROS-dependent manner29.”
From Air Pollution and Skin Diseases (2025) · cites this paper as [29]
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- Authors
- Ryu, Y. S., Kang, K. A., Piao, M. J., Ahn, M. J., Yi, J. M., Bossis, G., Hyun, Y.-M., Park, C. O., & Hyun, J. W.
- Affiliations
- Jeju National University (KR)
- Inje University (KR)
- Centre National de la Recherche Scientifique (FR)
- Yonsei University (KR)
- Corresponding author
- Hyun, Jin Won
- ORCID
- Venue
- Experimental & Molecular Medicine
- Published
- 2019-09
- Volume
- 51
- Issue
- 9
- Pages
- 1-14
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- PMC
- PMC6802667
- OpenAlex
- W2976086758
- Cited by
- 119
- References
- 40
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 18 · 2023: 14 · 2022: 20 · 2021: 20 · 2020: 16
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Research Foundation of Korea (2017R1A4A1014512)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- particulate matter, PM2.5, cellular senescence, keratinocytes, epigenetic modifications, DNA methylation, histone methylation, aryl hydrocarbon receptor, reactive oxygen species, oxidative stress, EZH2, MLL1, TET1, air pollution, skin aging
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3B, Animals, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Humans, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Proto-Oncogene Proteins, Skin, Keratinocytes, Cellular Senescence, Reactive Oxygen Species, Receptors, Aryl Hydrocarbon, Oxidative Stress, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Epigenesis, Genetic, Cell Proliferation, Mice, Myeloid-Lymphoid Leukemia Protein, Particulate Matter
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