Study shows how aging affects communication between skin cells

The disturbance of intercellular communication is one of the hallmarks of aging. In their new study, researchers from the University of LyonToyo University and Gattefossé SAS aimed to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues.

“The present study was therefore conducted to elucidate whether the characteristics of EVs released from cultured human keratinocytes can be modulated during aging process.”

The researchers 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, the researchers 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.

Aged EVs impact proliferation of young keratinocytes in 2D culture

Aged EVs impact proliferation of young keratinocytes in 2D culture. (A) Primary keratinocytes were treated with DAPI only (a, c) or by DAPI plus fluorescently labeled (CM-Dil) EVs from young keratinocytes culture medium (b, d). A part of image d is shown with higher magnification in (e, f, g). (B) Proliferation profile of young cultured keratinocytes treated with EVs purified from young or aged keratinocytes. DNA concentration in treated keratinocytes was measured 24 h, 48 h and 72 h after the beginning of the treatment. (*p-value **p-value n = 3 Student’s t-test). (C) Expression analysis of transcripts for P21, P16, P53, KRT1 (K1), KRT10 (K10) and loricrin in young keratinocytes treated with EVs from old keratinocytes. Data were normalized to the non-treated condition. (*p-value n = 3 Student’s t-test).

(A) Primary keratinocytes were treated with DAPI only (ac) or by DAPI plus fluorescently labeled (CM-Dil) EVs from young keratinocytes culture medium (bd). A part of image d is shown with higher magnification in (efg). (B) Proliferation profile of young cultured keratinocytes treated with EVs purified from young or aged keratinocytes. DNA concentration in treated keratinocytes was measured 24 h, 48 h and 72 h after the beginning of the treatment. (*p-value < 0.05. **p-value < 0.01. n = 3 Student’s t-test). (C) Expression analysis of transcripts for P21, P16, P53, KRT1 (K1), KRT10 (K10) and loricrin in young keratinocytes treated with EVs from old keratinocytes. Data were normalized to the non-treated condition.

“To conclude, we have shown here that aging modulates EVs abundance, function and microRNA content in human keratinocytes.”

SourceEurekAlert

Nedachi T, Bonod C, Rorteau J, Chinoune W, Ishiuchi Y, Hughes S, Gillet B, Bechetoille N, Sigaudo-Roussel D, Lamartine J. (2023) Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes. Aging (Albany NY) [Epub ahead of print]. [article]

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