Reduced Skin Stem Cell Motility in the Age-Related Loss of Regenerative Capacity

Old age brings with it a much reduced capacity for healing of skin injuries. Researchers here delve into the details, identifying factors that negatively influence the ability of keratinocyte stem cells to migrate. This offers the potential to override the reaction of these stem cells to age-related changes in the signaling environment. This sort of compensatory approach does nothing to address the underlying damage of aging that causes such changes in signaling. As a class of approach, compensation will never be as good as repair of damage, but compensatory signaling can in some cases still be beneficial enough to be worth pursuing as a basis for therapy.

With advanced age, a reduced skin wound healing ability is associated with the development of so-called chronic nonhealing disorders, such as diabetic ulcers and pressure sores. Skin stem cells, also called keratinocyte stem cells, are responsible for skin regeneration and wound closure through a process called re-epithelialization. "Live-imaging and computer simulation experiments showed that human skin stem cells motility is coupled with their proliferative and regenerative capacity and old stem skin cells have a significantly reduced motility."

To understand the mechanisms behind this reduced motility in old stem cells, researchers compared the wound healing and proliferative ability of skin stem cells derived from young mice (12 weeks old) and aged mice (19-25 months old). The experiments showed that a specific molecule, called EGFR (Epidermal Growth Factor Receptor), drives skin stem cell motility and that EGFR signalling is reduced in old stem cells. EGFR acts by preventing the degradation of a specific type of collagen, COL17A1, which is necessary to hold the layers of the skin together.

Interestingly, COL17A1 coordinates the movement of skin stem cells towards the injury by regulating actin and keratin filament networks in the cells. The researchers found that with age, a decrease in EGFR signalling occurs, leading to lower levels of COL17A1 and skin stem cells with reduced mobility that are less able to re-epithelialize the skin. "Although further investigations are still required, stabilizing COL17A1 by regulating its proteolysis is a promising therapeutic approach for improving the decline in skin regeneration observed with age."



An update on this ( and other things) as it pertains to skin aging

" The expression of COL17A1 is downregulated in aged skin. Consequently, compounds that activate COL17A1 expression represent new anti-ageing agents as they are expected to replenish epidermal stem cells. Screening of various chemical compounds for their ability to activate COL17A1 expression led to the identification of two potential pharmacologically active molecules, Y27632 and apocynin. As expected, Y27632 increased the self-renewing capability of epidermal stem cells in vitro.25"

Posted by: august33 at October 23rd, 2021 10:18 AM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.