Glycosylation Changes in Epidermal Stem Cells as a Biomarker of Aging

Researchers here analyze amounts and types of glycans in stem cells isolated from the skin of old and young mice. The differences observed might serve as a biomarker of aging, but also may be a contributing proximate cause of the age-related decline in skin stem cell function. As is usually the case, connecting downstream changes of this nature to the deeper causes of aging is a project yet to make any meaningful progress. It is also unclear as to whether glycan profile changes are a sizable cause of dysfunction versus all of the other possible proximate causes of stem cell functional decline.

Aging in the epidermis is marked by a gradual decline in barrier function, impaired wound healing, hair loss, and an increased risk of cancer. This could be due to age-related changes in the properties of epidermal stem cells and defective interactions with their microenvironment. Currently, no biochemical tools are available to detect and evaluate the aging of epidermal stem cells.

Cellular glycosylation is involved in cell-cell communications and cell-matrix adhesions in various physiological and pathological conditions. Here, we explored the changes of glycans in epidermal stem cells as a potential biomarker of aging. Using lectin microarray, we performed a comprehensive glycan profiling of freshly isolated epidermal stem cells from young and old mouse skin. Epidermal stem cells exhibited a significant difference in glycan profiles between young and old mice. In particular, the binding of a mannose-binder rHeltuba was decreased in old epidermal stem cells, whereas that of an α2-3Sia-binder rGal8N increased.

These glycan changes were accompanied by upregulation of sialyltransferase, St3gal2, and St6gal1 and mannosidase Man1a genes in old epidermal stem cells. The modification of cell surface glycans by overexpressing these glycogenes leads to a defect in the regenerative ability of epidermal stem cells in culture. Hence, our study suggests the age-related global alterations in cellular glycosylation patterns and its potential contribution to the stem cell function. These glycan modifications may serve as molecular markers for aging, and further functional studies will lead us to a better understanding of the process of skin aging.

Link: https://doi.org/10.1111/acel.13190

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