Dermal stiffness governs the topography of the epidermis and the underlying basement membrane in young and old human skin.
Kruppel-like factors
cell-matrix junctions
cellular mechanotransduction
extracellular matrix
skin aging
ultrastructure
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
12 Mar 2024
12 Mar 2024
Historique:
revised:
05
01
2024
received:
12
10
2023
accepted:
08
01
2024
medline:
13
3
2024
pubmed:
13
3
2024
entrez:
13
3
2024
Statut:
aheadofprint
Résumé
The epidermis is a stratified epithelium that forms the outer layer of the skin. It is composed primarily of keratinocytes and is constantly renewed by the proliferation of stem cells and their progeny that undergo terminal differentiation as they leave the basal layer and migrate to the skin surface. Basal keratinocytes rest on a basement membrane composed of an extracellular matrix that controls their fate via integrin-mediated focal adhesions and hemidesmosomes which are critical elements of the epidermal barrier and promote its regenerative capabilities. The distribution of basal cells with optimal activity provides the basement membrane with its characteristic undulating shape; this configuration disappears with age, leading to epidermal weakness. In this study, we present an in-depth imaging analysis of basal keratinocyte anchorage in samples of human skin from participants across the age spectrum. Our findings reveal that skin aging is associated with the depletion of hemidesmosomes that provide crucial support for stem cell maintenance; their depletion correlates with the loss of the characteristic basement membrane structure. Atomic force microscopy studies of skin and in vitro experiments revealed that the increase in tissue stiffness observed with aging triggers mechanical signals that alter the basement membrane structure and reduce the extent of basal keratinocyte anchorage, forcing them to differentiate. Genomic analysis revealed that epidermal aging was associated with mechanical induction of the transcription factor Krüppel-like factor 4. The altered mechanical properties of tissue being a new hallmark of aging, our work opens new avenues for the development of skin rejuvenation strategies.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14096Subventions
Organisme : Région Auvergne-Rhône-Alpes
Informations de copyright
© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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