Research can be interesting even if the future development of therapies based on that research seems challenging. Today's open access paper is chiefly interesting for its outline of the developmental and ongoing relationship between skin and the brain, and the signaling that passes between the two. It is intriguing that this relationship means that one can harvest extracellular vesicles generated by cells in the brain and use them to change skin cell behavior in order to produce scar free regeneration from injury.
However, to make this into a therapy would require either (a) a much greater understanding of the specific signaling mechanisms involved, in order to replace the vesicles with some other way to manipulate those mechanisms, or (b) the ability to maintain human organoid brain tissues at scale for the purpose of harvesting vesicles. Since the researchers harvested the vesicles directly from brain tissue, it is unclear as to which cells produced them, and which of the various types of vesicle are important to the end result. Other options seem more impractical, such as access to a lot of waste cerebrospinal fluid from young individuals. So it seems best to look on this as a tool that might lead to a better understanding of targets to suppress scarring in skin tissue, and a line of research that will take some time to come to a practical basis for therapy.
The intricate relationship of the "brain-skin axis" has been described in the literature, with both considered to originate from the same germ layer. The neuroendocrine networks have long been well recognized, especially with the discovery of corticotropin-releasing factor (CRF), which defines the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis. The skin has been identified as a neuroendocrine organ, expressing a variety of brain and pituitary hormones, as well as multiple neuropeptides, to regulate local homeostasis in response to stress. In contrast, abnormal mental states such as stress can promote skin aging.
It remains unclear whether cultivating a healthy, youthful brain can promote the healing of skin wounds in older adults. While the tight regulatory crosstalk between brain and skin has been represented in cellular phenotypic alterations, the underlying mechanisms remain to be elucidated. Extracellular vesicles (EVs) are membrane-bound vesicles expelled from cells, body fluids, and tissue into the extracellular space and can carry materials (proteins, RNA, and DNA) from one cell to another. EVs from elderly subjects are mediators of the progressive deterioration of age-related tissue dysfunction over time. In recent decades, EV therapies have shown promise in the field of aging.
In this study, we hypothesized that brain-EVs, as a novel paradigm, regulate aging fibrocyte metabolism and functions by delivering mitochondrion-related proteins. We identified youthful brain-derived extracellular vesicles (YBEVs) and created a composite hydrogel material incorporating YBEVs that encourages scarless wound healing in aged skin. We found that YBEVs reduce the expression of senescence, senescence-associated secretory phenotypes, and inflammation-associated proteins, and even restore dysfunction in senescent cells. Furthermore, by encouraging collagen deposition, angiogenesis, epidermal and dermal regeneration, and folliculogenesis, we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats. The pro-repairing speed and effect of this composite hydrogel even matched that of young rats.
Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs, some of which may play a role in the regulation of skin energy intake, particularly through oxidative phosphorylation and mitochondrial function. In conclusion, the findings suggest that maintaining a youthful brain could potentially alleviate skin aging, and the proposed YBEV-containing hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.
View the full article at FightAging
