A healthy aging research update from Amway R&D
The development
Amway scientists and researchers at the Technical University of Munich (TUM) used state-of-the-art molecular modeling and cutting-edge computational screening to help the teams more quickly and efficiently identify candidate plant-derived molecules for further research.
Why it is significant
This represents a significant advancement in scientific research. The approach combined precision and innovation, leveraging the Collective Molecular Activities of Useful Plants (CMAUP)1 database. The database consists of 50,000 phytochemicals from 10,000 plant species. This resource enabled a highly targeted and customized search for novel plant-based ingredients and in vitro parameters. While further testing is necessary, this development marks a major step forward in understanding potential efficiency and effectiveness.
Plant-derived compounds were meticulously screened through advanced in silico (computer modeling) methods by Khushboo Singh, PhD, Amway senior research scientist specializing in computational biochemistry. These findings were validated through the work of Professor Karima Djabali, PhD, an expert in cellular aging at the TUM School of Medicine, focusing on fibroblasts (cells responsible for producing and maintaining connective tissue) and stem cells.
This method of analysis enabled highly focused, tailored research targeted to identifying novel ingredients for specific targets – an approach that is well established in pharmaceutical development but is cutting-edge in skin science. By focusing on molecular mechanisms and defined molecular targets, the method significantly increased the likelihood that the selected biomolecules exhibit the desired biological activity. It also accelerated the discovery process and potentially saved years of work sifting through a vast array of plant compounds.
“This is our first jump into stem cells, and the pathways identified in this work are all new to us,” said Jesse Leverett, Amway Fellow, Open Innovation. “The science is all about the leading-edge tools and expertise we have internally at Amway that enable these breakthrough discoveries, and the unique power of coupling that with the expertise of our global research collaborators.” A peer-reviewed article covering a part of the research was published in the journal Biomolecules2.
Human skin, the body’s largest organ, undergoes continuous renewal, but repeated damage from the external environment significantly impacts its resilience and ability to repair itself. Both internal and external factors contribute to this process, impairing skin function and leading to visible changes such as wrinkles, dryness, thinning, pigmentation changes and reduced barrier effectiveness. Building on Professor Djabali’s work on the pathways leading to skin stem cells to become unhealthy with damage, the team sought to identify plant molecules that inhibit those pathways.
“Professor Djabali identified two proteins associated with cellular dysfunction (called JAK1 and JAK2), and then the work began to identify plant molecules that are able to bind to them, but it was a moving target because JAK proteins are known to undergo large conformational changes upon compound binding,” Leverett said. “We knew it would require an approach that would enable us to focus our testing very precisely, beyond what typically is done in skin research to find novel ingredients. This is where Khushboo’s interdisciplinary expertise in computational biochemistry became essential.”
Singh modeled the JAK proteins and analyzed their pocket dynamics and flexibility. She then utilized the CMAUP database to perform virtual screening and identify phytochemicals that could potentially inhibit the JAK proteins. Creating the model and conducting the screening took three months, involving an exhaustive literature review, inputting extensive biochemical data. Ultimately, this process allowed the team to visualize the structure of normal proteins on the computer screen and understand how the binding of top phytochemicals could inhibit their bioactivity.
“It was essential to understand how the proteins change shape when they bind with molecules,” Singh explained. “By applying a specialized algorithm to simulate these interactions, we could predict which plant-derived compounds would have the highest potential for binding to JAK1 and JAK2. We have well-established indicators of positive activity, and we can show exactly where and how these molecules bind to the proteins.
“This is a huge advantage over the traditional approach of randomly testing plant materials,” Singh continued. “This approach not only saved us significant time but also allowed us to narrow down the most promising candidates more efficiently.”
What happens next
The modeling results showed that some candidate molecules were associated with improved cell proliferation, improved cellular health markers, and enhanced autophagy (cells’ natural ability to recycle their damaged components). These findings suggest that the tested molecules have the potential to reduce cellular changes due to damage from aging and accelerated damage from the external environment. However, further testing is required to validate the research.
“The in silico modeling greatly increased our confidence in our choices over testing plant compounds at random though trial and error” Leverett said. “That’s the advantage of these advanced capabilities, combined with our internal scientific expertise and strong collaboration. I believe this work put us years ahead in our research.”
1 Collected Molecular Activities of Useful Plants. Dongyue Hou et al. CMAUP database update 2024: extended functional and association information of useful plants for biomedical research. Accessed at https://pubmed.ncbi.nlm.nih.gov/37897343/
2 Ramona Hartinger, Khushboo Singh, Jesse Leverett, Karima Djabali. Enhancing Cellular Homeostasis: Targeted Botanical Compounds Boost Cellular Health Functions in Normal and Premature Aging Fibroblasts. Published in Biomolecules 2024. Accessed at https://pmc.ncbi.nlm.nih.gov/articles/PMC11506649/
