The skin is the only organ that shows age more profoundly. While researchers have hypothesized about the ravages of time on skin and also the epidermal stem cells that undergo differentiation to restore the external layer of the skin, no suitable method is available to assess their aging at the molecular level.
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Scientists from the University of Tsukuba and the National Institute of Advanced Industrial Science and Technology (AIST) have now demonstrated that alterations in the complex sugars, known as glycans, that cover the surface of epidermal stem cells can act as a promising biological marker for aging.
As the largest human organ, the skin acts as a significant barrier against fluid loss and infection. Aging damages wound healing and environmental defenses, while raising cancer risk and hair fall.
Cellular glycosylation is a major process underlying epidermal function in disease and health. This process mediates adhesions between cells and matrices, as well as interactions between cells.
During glycosylation, glycans bind to proteins; the profile of all glycans in and on a cell—collectively known as “the cell glycome”—could mirror its functional scope and act as an index of its age.
The scientists initially separated epidermal stem cells from the skin of old and young laboratory mice, including interfollicular epidermal cells as well as hair follicle cells.
Such cells use the lectin microarray platform to go through glycan profiling; this method employs lectins—that is, proteins that bind particular glycans—and allow glycome analysis even for sparsely dispersed cells in tissues.
Our results clearly showed that high mannose-type N-glycans are replaced by a2-3/6 sialylated complex type N-glycans in older epidermal stem cells. We followed this with gene expression analysis; this revealed up-regulation of a glycosylation-related mannosidase and two sialyltransferase genes, suggesting that this ‘glycome shift’ may be mediated by age-modulated glycosyltransferase and glycosidase expression.”
Hiromi Yanagisawa, Study Senior Author and Professor, University of Tsukuba
Then, to find out whether the changes in the glycan were the cause or simply the outcome of aging, the researchers effectively overexpressed the up-regulated glycogenes in primary epidermal mouse keratinocytes in vitro.
These keratinocytes exhibited increased Sia and decreased mannose alterations, simulating the in vivo glycosylation pattern of aging epidermal stem cells. Moreover, the reduced potential of the keratinocytes to proliferate indicated that such modifications may reflect the declining potential of the aging epidermal stem cells to multiply.
Professor Aiko Sada, presently the Principal Investigator at Kumamoto University and Professor Hiroaki Tateno from AIST, described the implications of the study outcomes, “Our work is broadly targeted at investigating stem cell dysfunction specifically in aging skin. Future advances may help manage skin disorders at the stem cell level, including age-related degenerative changes, impaired wound healing and cancer.”
Professors Sada and Tateno are the study’s co-corresponding authors.
Oinam, L., et al. (2020) Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging. Aging Cell. doi.org/10.1111/acel.13190.