“Age is an issue of mind over matter. If you don’t mind, it doesn’t matter.” Mark Twain
Not everyone shares Mark Twain´s carefree view on aging. Quite the contrary, many individuals fear getting older. Therefore, effective strategies to prevent, or even reverse aging are highly demanded. However, clinically relevant research models to identify key players of human organ aging, and to test promising anti-aging or rejuvenating candidate agents, are still lacking.
In our latest study, recently published in Science Advanced, we developed a pre-clinical model for human organ rejuvenation. In collaboration with the research group of Prof. Amos Gilhar in Israel, we established a humanized mouse model for skin aging by transplanting human skin samples, obtained from elderly individuals, onto ‘young’ mice. We observed rejuvenation of the transplanted, ‘old’ human skin, caused by molecular factors present in the blood stream and skin of young mice.
One month after transplantation, the (formerly) old, human skin transplants showed, for instance, increased amounts of collagen and HABP, a protein that has an important role in stabilizing hyaluronic acid. Interestingly, collagen and hyaluronic acid are both associated with young skin, and are present in various cosmeceutical products. Additionally, the (formerly) old human skin transplants were pervaded by an enhanced number of newly formed blood vessels. Of note, it is broadly believed that a decreased vascular density is a crucial factor preceding organ aging.
We wanted to dig deeper, and discover the key factors that regulate the observed rejuvenation process. Determining these factors could help to identify druggable targets, which can be used for the therapeutic intervention of aging. In this context, we identified an important role for VEGF-A (vascular endothelial growth factor A), a signalling molecule that regulates blood vessel formation. Great amounts of VEGF-A are present in the skin and blood stream of young mice. As soon as this VEGF-A reaches the ‘old’ human skin transplant, it induces a signalling cascade, which results into the stimulation and production of human VEGF-A inside the skin transplant, which is ultimately mediating the observed anti-aging effects. Interestingly, when we experimentally depleted VEGF-A, the rejuvenation process of the transplanted, ‘old’ human skin samples was hampered. In addition, experimental supplementation of VEGF-A in our well established human skin organ culture improved aging parameters. Thus, VEGF-A signalling is required to rapidly rejuvenate human skin, and therefore might present an interesting target to halt or reverse the aging process.
Taken together these findings suggest that our humanized mouse model and skin organ culture model are very well fit to not only study human skin aging, but also human organ aging in general. Since human skin is relatively easy accessible, and the generated findings can be reliably translated into clinical reality, our model can be utilized to discover and identify targets, and to pre-clinically investigate anti-aging- or rejuvenating agents.
Keywords: skin aging, humanized mouse model, human skin organ culture, VEGF-A
Read the full story here: Human organ rejuvenation by VEGF-A: Lessons from the skin
#anti-aging #scienceofaging #rejuvenation #skinaging