Skin aging is a complex process. In addition to changing processes in the body, sunlight and pollution also have an impact. When these two factors come together, researchers refer to it as the urban exposome.
The mechanisms involved in the body are also complex: fat, protein and sugar metabolism contribute to skin aging, as does the ability of the tissue to communicate and regenerate. This interaction will be analyzed with high precision at the cellular level in the interdisciplinary SKINMAGINE project.
“This is a very interdisciplinary project,” explains Markus Schosserer, Senior Scientist at the Institute of Molecular Biotechnology at the University of Natural Resources and Life Sciences (BOKU) in Vienna, Austria. Characterizing skin changes with individual methods is very difficult. That’s why dermatologists at the Medical University of Vienna, biotechnologists at BOKU and chemists at the Vienna University of Technology are pooling their methods and knowledge. Together, they want to combine mass spectroscopy with other imaging techniques to apply multimodal analytical methods. The French fashion and cosmetics group Chanel is also part of the team.
BOKU has been conducting research into skin aging for 20 years. The original idea was to make cells immortal to use them for biotechnological processes, explains Schosserer: “Cells from the human body only have a limited life span. At some point, they stop dividing. With immortal cells, we could constantly reproduce cells from the same donor and then use them as test systems to produce biotechnological products.”
Schosserer has established Raman microscopy technology for cell cultures and tissue samples at BOKU. This technology makes it possible to study cellular processes in living organisms and offers different imaging methods – from point measurements to scanning an entire piece of tissue. In an interview with Innovation Origins, Schosserer explains the project setup.
What is the state of the art in skin aging research? What research are you connecting with?
This is already the second project in which we are working with Chanel on new findings in skin aging. In the first project, Professor Erwin Tschachler from the Institute of Dermatology at the Medical University of Vienna approached us because he was interested in our models for cellular skin aging. At that time, we started to jointly develop models that would allow us to test cells outside the body.
It is very important for the cosmetics industry to move away from animal models. Mice are not good models for human skin aging, as their skin looks very different from ours. We have helped develop three-dimensional models from human skin cells that accurately represent skin aging. To do this, we incorporated senescent cells into an artificial skin model. Senescent cells are cells that we age in tissue culture. The more senescent skin cells we put into this skin model, the more it resembled old skin. This allowed us to reproduce the actual skin aging process in which the epidermis, the top layer of skin, becomes thinner and thinner.
What cells do you use to research the mechanisms of skin aging?
We obtain the cells from skin biopsies that are left over from surgical procedures. Most of the time, these are liposuctions on the abdomen for aesthetic purposes. The abdominal skin is suitable because the abdomen is not exposed to much UV radiation so the skin cells are not yet damaged. This gives us access to the skin of younger and older donors, which we can examine ex vivo.
Because of our cell biology background, we also do a lot with cell culture, working both with low-complexity cultures of a single cell type as well as with artificial skin equivalents. This means that we mix different cells together and then use them to grow artificial skin.
The project also aims to build up basic knowledge. What questions would you like to answer?
We know that senescent cells contribute to skin aging but would like to understand the mechanisms better. From the BOKU perspective, I am particularly interested in protein synthesis. We have known for a long time that protein synthesis in general plays a major role in aging processes in the organism. For example, we know that an organism that consumes less protein, i.e., synthesizes less protein, lives longer. Now we would like to find out whether this also causes cells to age sooner or later at the cellular level – and whether we can reverse this. But to do this we need to understand the aging processes in detail. We need to understand how protein synthesis works and how aging changes the molecular machines that produce protein in the cell. (Note: Protein synthesis is the new formation of proteins in cells, in which proteins are built from amino acids according to genetic information).
You want to analyze skin aging due to the urban exposome. How do you represent these changes?
This is very complex because many factors interact: Genetics, UV rays and various exhaust particles which may also differ depending on their origin. That’s why we first try to keep things as simple as possible and analyze them in vitro, that is, with natural material on our model. To be able to remove the genetic variance, we take cells from only a few donors. Then we build our artificial skin and expose it to standardized UV radiation and precisely defined concentrations of dirt and fine dust particles. This enables us to study what changes the urban exposome causes in the skin at both the chemical and cellular levels. Later, we will also study the process in samples from donors to see whether the results can be transferred.
So the starting position is the ideal skin, the skin on the abdomen?
Exactly, and we then let it age in a standardized way in our laboratory.
In this project, you work with multimodal imaging, combining different imaging microscope techniques. Could you describe that in more detail?
The problem with Raman microspectroscopy is that we generate spectra that are very complex. Each macromolecule in the cell generates its own spectrum and that leads to overlap. Keeping track of which molecule is making which change at any given moment is extremely difficult.
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When we combine different imaging techniques, we get comprehensive information about biological processes. First, however, this image information has to be put together. This is difficult because these images have different scales, distortions sometimes occur and the information they contain varies greatly. To then superimpose this with precision down to a micrometer or even a nanometer is not easy. So the big challenge falls with the chemists and bioinformaticians from the Vienna University of Technology who assemble the various microscope images.
This project also seeks to find a method enabling researchers to make an immediate statement about a person’s skin condition by taking a sample directly from the skin surface and introducing it into the device online. How will this work?
First of all, we want to establish the method with our cell model. However, our cooperation partners are already working with test persons to create portable Raman probes. In this case, you only need to scan with the probe over your hand, for example, to examine the spectra. We have a much higher resolution with our model and are working on transferring the information generated on our model to the in vivo situation.
Does Chanel want to develop plant-based products in the project?
We already found a plant extract from goldenrod in our previous collaboration with Chanel that can slow down the signs of skin aging in our in vitro models. Chanel was later able to verify these results on test subjects. The top layer of their skin really did get a little thicker. Our biological models are quite abstract, so seeing that they really translate to humans is a great experience.
We will do the same in the new project. Again, we will get plant-based extracts or other active substances from Chanel and then study whether they can delay or reverse skin aging. However, we are mainly testing pure extracts. A finished skincare product, of course, consists of many other components and we do not know how it is ultimately formulated. The testing of skincare extracts and products on test subjects is mainly done by our cooperation partner Chanel.
Thank you for the interview.
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