Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging

Abstract 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, senesce...

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Autores principales:	Regina Weinmüllner, Barbara Zbiral, Adnan Becirovic, Elena Maria Stelzer, Fabian Nagelreiter, Markus Schosserer, Ingo Lämmermann, Lisa Liendl, Magdalena Lang, Lucia Terlecki-Zaniewicz, Orestis Andriotis, Michael Mildner, Bahar Golabi, Petra Waidhofer-Söllner, Karl Schedle, Gerhard Emsenhuber, Philipp J. Thurner, Erwin Tschachler, Florian Gruber, Johannes Grillari
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/ca3243e6958741a2b69658933a36f4cf
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spelling	oai:doaj.org-article:ca3243e6958741a2b69658933a36f4cf2021-12-02T13:30:49ZOrganotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging10.1038/s41514-020-0042-x2056-3973https://doaj.org/article/ca3243e6958741a2b69658933a36f4cf2020-03-01T00:00:00Zhttps://doi.org/10.1038/s41514-020-0042-xhttps://doaj.org/toc/2056-3973Abstract 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.Regina WeinmüllnerBarbara ZbiralAdnan BecirovicElena Maria StelzerFabian NagelreiterMarkus SchossererIngo LämmermannLisa LiendlMagdalena LangLucia Terlecki-ZaniewiczOrestis AndriotisMichael MildnerBahar GolabiPetra Waidhofer-SöllnerKarl SchedleGerhard EmsenhuberPhilipp J. ThurnerErwin TschachlerFlorian GruberJohannes GrillariNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 6, Iss 1, Pp 1-7 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Regina Weinmüllner Barbara Zbiral Adnan Becirovic Elena Maria Stelzer Fabian Nagelreiter Markus Schosserer Ingo Lämmermann Lisa Liendl Magdalena Lang Lucia Terlecki-Zaniewicz Orestis Andriotis Michael Mildner Bahar Golabi Petra Waidhofer-Söllner Karl Schedle Gerhard Emsenhuber Philipp J. Thurner Erwin Tschachler Florian Gruber Johannes Grillari Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
description	Abstract 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.
format	article
author	Regina Weinmüllner Barbara Zbiral Adnan Becirovic Elena Maria Stelzer Fabian Nagelreiter Markus Schosserer Ingo Lämmermann Lisa Liendl Magdalena Lang Lucia Terlecki-Zaniewicz Orestis Andriotis Michael Mildner Bahar Golabi Petra Waidhofer-Söllner Karl Schedle Gerhard Emsenhuber Philipp J. Thurner Erwin Tschachler Florian Gruber Johannes Grillari
author_facet	Regina Weinmüllner Barbara Zbiral Adnan Becirovic Elena Maria Stelzer Fabian Nagelreiter Markus Schosserer Ingo Lämmermann Lisa Liendl Magdalena Lang Lucia Terlecki-Zaniewicz Orestis Andriotis Michael Mildner Bahar Golabi Petra Waidhofer-Söllner Karl Schedle Gerhard Emsenhuber Philipp J. Thurner Erwin Tschachler Florian Gruber Johannes Grillari
author_sort	Regina Weinmüllner
title	Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
title_short	Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
title_full	Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
title_fullStr	Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
title_full_unstemmed	Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
title_sort	organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/ca3243e6958741a2b69658933a36f4cf
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Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging

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