Research Paper Volume 15, Issue 22 pp 12702—12722
Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes
- 1 Skin Functional Integrity group, Laboratory for Tissue Biology and Therapeutics Engineering (LBTI) CNRS UMR5305, University of Lyon, Lyon, France
- 2 Department of Life Science, Toyo University, Gunma, Japan
- 3 IGFL CNRS UMR5242, ENS de Lyon, University of Lyon, Lyon, France
- 4 Gattefossé SAS, St Priest, France
Received: December 21, 2022 Accepted: October 15, 2023 Published: November 27, 2023
https://doi.org/10.18632/aging.205245How to Cite
Copyright: © 2023 Nedachi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.
Abbreviations
EVs: Extracellular Vesicles; DLS: Dynamic Light Scattering; MVs: MicroVesicles; RT-PCR: Reverse Transcription Polymerase Chain Reaction; RHE: Reconstructed Human Epidermis; HPK: Human Primary Keratinocytes.