Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis

Abstract Cellular senescence is an irreversible growth arrest that occurs as a result of damaging stimuli, including DNA damage and/or telomere shortening. Here, we investigate histone variant H2A.J as a new biomarker to detect senescent cells during human skin aging. Skin biopsies from healthy volu...

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Autores principales:	Claudia E. Rübe, Caroline Bäumert, Nadine Schuler, Anna Isermann, Zoé Schmal, Matthias Glanemann, Carl Mann, Harry Scherthan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/d87dc7743f364e58867d576df1284703
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spelling	oai:doaj.org-article:d87dc7743f364e58867d576df12847032021-12-02T13:27:08ZHuman skin aging is associated with increased expression of the histone variant H2A.J in the epidermis10.1038/s41514-021-00060-z2056-3973https://doaj.org/article/d87dc7743f364e58867d576df12847032021-04-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00060-zhttps://doaj.org/toc/2056-3973Abstract Cellular senescence is an irreversible growth arrest that occurs as a result of damaging stimuli, including DNA damage and/or telomere shortening. Here, we investigate histone variant H2A.J as a new biomarker to detect senescent cells during human skin aging. Skin biopsies from healthy volunteers of different ages (18–90 years) were analyzed for H2A.J expression and other parameters involved in triggering and/or maintaining cellular senescence. In the epidermis, the proportions of H2A.J-expressing keratinocytes increased from ≈20% in young to ≈60% in aged skin. Inverse correlations between Ki67- and H2A.J staining in germinative layers may reflect that H2A.J-expressing cells having lost their capacity to divide. As cellular senescence is triggered by DNA-damage signals, persistent 53BP1-foci, telomere lengths, and telomere-associated damage foci were analyzed in epidermal keratinocytes. Only slight age-related telomere attrition and few persistent nuclear 53BP1-foci, occasionally colocalizing with telomeres, suggest that unprotected telomeres are not a significant cause of senescence during skin aging. Quantification of integrin-α6+ basal cells suggests that the number and function of stem/progenitor cells decreased during aging and their altered proliferation capacities resulted in diminished tissue renewal with epidermal thinning. Collectively, our findings suggest that H2A.J is a sensitive marker of epidermal aging in human skin.Claudia E. RübeCaroline BäumertNadine SchulerAnna IsermannZoé SchmalMatthias GlanemannCarl MannHarry ScherthanNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geriatrics RC952-954.6
spellingShingle	Geriatrics RC952-954.6 Claudia E. Rübe Caroline Bäumert Nadine Schuler Anna Isermann Zoé Schmal Matthias Glanemann Carl Mann Harry Scherthan Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
description	Abstract Cellular senescence is an irreversible growth arrest that occurs as a result of damaging stimuli, including DNA damage and/or telomere shortening. Here, we investigate histone variant H2A.J as a new biomarker to detect senescent cells during human skin aging. Skin biopsies from healthy volunteers of different ages (18–90 years) were analyzed for H2A.J expression and other parameters involved in triggering and/or maintaining cellular senescence. In the epidermis, the proportions of H2A.J-expressing keratinocytes increased from ≈20% in young to ≈60% in aged skin. Inverse correlations between Ki67- and H2A.J staining in germinative layers may reflect that H2A.J-expressing cells having lost their capacity to divide. As cellular senescence is triggered by DNA-damage signals, persistent 53BP1-foci, telomere lengths, and telomere-associated damage foci were analyzed in epidermal keratinocytes. Only slight age-related telomere attrition and few persistent nuclear 53BP1-foci, occasionally colocalizing with telomeres, suggest that unprotected telomeres are not a significant cause of senescence during skin aging. Quantification of integrin-α6+ basal cells suggests that the number and function of stem/progenitor cells decreased during aging and their altered proliferation capacities resulted in diminished tissue renewal with epidermal thinning. Collectively, our findings suggest that H2A.J is a sensitive marker of epidermal aging in human skin.
format	article
author	Claudia E. Rübe Caroline Bäumert Nadine Schuler Anna Isermann Zoé Schmal Matthias Glanemann Carl Mann Harry Scherthan
author_facet	Claudia E. Rübe Caroline Bäumert Nadine Schuler Anna Isermann Zoé Schmal Matthias Glanemann Carl Mann Harry Scherthan
author_sort	Claudia E. Rübe
title	Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
title_short	Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
title_full	Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
title_fullStr	Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
title_full_unstemmed	Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis
title_sort	human skin aging is associated with increased expression of the histone variant h2a.j in the epidermis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d87dc7743f364e58867d576df1284703
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Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis

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