Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
Open accessAbstract
Skin aging is driven by intrinsic and extrinsic factors impacting on skin functionality with progressive age. One factor of this multifaceted process is cellular senescence, as it has recently been identified to contribute to a declining tissue functionality in old age. In the skin, senescent cells have been found to markedly accumulate with age, and thus might impact directly on skin characteristics. Especially the switch from young, extracellular matrix-building fibroblasts to a senescence-associated secretory phenotype (SASP) could alter the microenvironment in the skin drastically and therefore promote skin aging. In order to study the influence of senescence in human skin, 3D organotypic cultures are a well-suited model system. However, only few “aged” skin- equivalent (SE) models are available, requiring complex and long-term experimental setups. Here, we adapted a previously published full-thickness SE model by seeding increasing ratios of stress-induced premature senescent versus normal fibroblasts into the collagen matrix, terming these SE “senoskin”. Immunohistochemistry stainings revealed a shift in the balance between proliferation (Ki67) and differentiation (Keratin 10 and Filaggrin) of keratinocytes within our senoskin equivalents, as well as partial impairment of skin barrier function and changed surface properties. Monitoring of cytokine levels of known SASP factors confirmedly showed an upregulation in 2D cultures of senescent cells and at the time of seeding into the skin equivalent. Surprisingly, we find a blunted response of cytokines in the senoskin equivalent over time during 3D differentiation.
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HSEs are used to investigate wound healing, aging, and various diseases.
“HSEs are used to investigate various aspects of normal and abnormal skin biology, including wound healing [40,41], aging [42,43], and the study of various diseases [18].”
From Diversity of human skin three-dimensional organotypic cultures (2024) · cites this paper as [43]
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- Authors
- Weinmüllner, R., Zbiral, B., Becirovic, A., Stelzer, E. M., Nagelreiter, F., Schosserer, M., Lämmermann, I., Liendl, L., Lang, M., Terlecki-Zaniewicz, L., Andriotis, O., Mildner, M., Golabi, B., Waidhofer-Söllner, P., Schedle, K., Emsenhuber, G., Thurner, P. J., Tschachler, E., Gruber, F., & Grillari, J.
- Affiliations
- BOKU University (AT)
- Austrian Cluster for Tissue Regeneration (AT)
- TU Wien (AT)
- Medical University of Vienna (AT)
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
- Corresponding author
- Grillari, Johannes
- ORCID
- Venue
- npj Aging and Mechanisms of Disease
- Published
- 2020-03-06
- Volume
- 6
- Issue
- 1
- Pages
- 4-4
- ISSN
- 2056-3973 (ISSN-L)
- PMC
- PMC7060247
- OpenAlex
- W3009524618
- Cited by
- 103
- References
- 24
- Citations by year
- 2026: 5 · 2025: 22 · 2024: 18 · 2023: 19 · 2022: 11 · 2021: 22 · 2020: 6
- FWCI
- 8.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Aging and Mechanisms of Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Austrian Science Fund (FWF: I2514)
- Christian Doppler Forschungsgesellschaft
- PhD Programme BioToP – ‘Biomolecular technolgy of proteins’
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- skin aging, cellular senescence, senescence-associated secretory phenotype, stress-induced premature senescence, fibroblasts, keratinocytes, skin barrier function, cytokines, extracellular matrix
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