The Lingo Simplified: Paths for Communication
Signal to the Cell – Not unlike our modern smartphones, biological cells communicate by sending and receiving signals. Signals may come from other cells in a cascade of cellular processes or signals can be transmitted into a cell by binding to a matching, specific surface receptor site.
A Signaling Pathway – Like the game of telephone, once the message is transferred, it is passed through the cell by groups of molecules that work together with each molecule modifying the next message to control one or more cell functions.
In the process of communication, the signals can be activated, deactivated, modulated, amplified, branched out, multiplied, or spread by signaling proteins such as growth factors, cytokines, and other signaling molecules.
Multiple Signals Integrated – Combinations of signals are important. Each step in a signaling pathway provides an opportunity for cross-talk between different signals to initiate an appropriate response. Collectively the cells work together to transmit information to their final destination, which could be maintaining skin homeostasis or responding to injury.
Cell-communicating ingredients, theoretically, have the ability to utilize existing chemical pathways and receptors that regulate skin functions. There are numerous approaches and advantages with cell-communicating ingredients now available, with a focus targeting a variety of visible signs of aging presented below.

How We Demonstrate Cell Communication is Happening
In vitro test methods are the most common for identifying cellular communication. In vitro methods involve using cells and tissues grown in the laboratory. With culture models and chemical cell marking, cellular responses can be measured with the ingredient versus a known standard or placebo. By analyzing a gene array before and after treatment, identification of the up-regulation and down-regulation of the gene expression can be quantified and distinguished from the known influences and function of the cellular pathways. Research is constantly emerging on deciphering how cells communicate with each other and many ingredient companies devise unique scientific methods to propose the action of their ingredient. The old proverb, “the proof is in the pudding is in the eating” now comes into play to substantiate the in vitro findings. In vivo testing involves measurements on live subject’s skin. The measurements can include a variety of instrumentation analysis, photography comparison, and perception evaluations to demonstrate perceivable results after treatment of the applied topical ingredients. Ingredients supported by in vitro testing for proof-of-concept and in vivo observations are essential for cosmetic claims and the success of products formulated based on science for efficacy.

Communication Targeting Anti-Aging
A key point to remember is that cell communication becomes reduced and less effective with age. The importance of communication between layers of skin plays a critical role in the design of cosmetic ingredients in the anti-aging category.
By choosing an ingredient that will have an impact on a particular signaling pathway, we can communicate by using signals or receptors from the outer skin layer to prompt communication between the deeper layers of skin. In a different approach beyond common delivery systems, a new 2014 pentapeptide ingredient was shown to enhance in vitro expression of stratifin, an epidermal signaling protein that optimizes cross-talk between the epidermis and dermis. Stratifin is released by the keratinocytes and the cross-talk between the keratinocytes and dermal fibroblasts is able to begin. The cross-talk signals interact and trigger the pathways that initiate the dermal remodeling and reorganization process. It is an interesting approach as extracellular matrix (ECM) is signaled to degrade and thus new ECM is synthesized. Due to the dermal remodeling, the in vivo clinical study results indicate this ingredient would be ideal for firming, smoothing, and reducing the visible signs of aging.
Multiple anti-aging ingredients concentrate on cell communication between the epidermis and dermis and Mibelle Biochemistry’s crocus chrysanthus bulb extract uses cell-to-cell signaling via growth factors to increase the communication. The release of these signaling compounds creates a cascade of cellular processes that instruct dermal cells to activate the synthesis of collagen and elastin fibers. In assays with dermal cells, the growth factor messengers stimulated the synthesis of elastin and Mibelle’s in vivo studies support claims of increased skin collagen and elastin after 14 days of application.
With various strategies to counteract the visible signs of aging, there is an emergence of new cell-communicating ingredients that not only activate the communication, but regulate particular signals for different anti-aging benefits. There is also a wide variety of cell-communicating ingredient offerings while promoting the use of natural ingredients; one recent addition is a yeast extract (Pichia anomala). The “inflammaging” strategy is a regulation approach by limiting the pro-inflammatory cytokines between senescent cells and their environment. Perception studies report 90 percent of participants indicated that lines and wrinkles were less visible and their skin was smoother, validating the in vitro findings.
Silab’s 2014 C&T award-winning ingredient, paeonia albiflora root extract normalizes negative pro-inflammatory messages between the reticular dermis and hypodermis. Numerous in vitro studies were performed, and three clinical in vivo studies were conducted substantiating an effect of remodeling of the contour of the face in 42 days.
With Evonik’s ingredient, caprooyl phytosphingosine, simplifying the multiple routes of communication, benefits and delivery has proven to be challenging! Caprooyl phytosphingosine is a short-chain ceramide with significant in vitro and supporting in vivo tests. The ingredient was found to stimulate various cross-talk between cells throughout the skin layers by not only having function in the epidermis as a signaling molecule for keratinocyte differentiation and keratinocyte communication to fibroblasts, but by having the ability to penetrate to deeper skin layers. Beneficial cross-talk between adipocytes and fibroblasts is increased, which results in additional support of dermal ECM. Tightened skin structure, plumped tone, and visibly reshaped skin are benefits of the material.
When speaking of anti-aging, it would be remiss not to mention stem cells. The power of stem cells is their ability to know when and how to act by communicating with other cells. By sending signals back and forth, the stem cells go where they need to go and differentiate by interpreting the signals they receive. SEPPIC’s material that benefits our stem cells via cell-communication is sodium cocoyl alaninate, which helps maintain the regeneration potential of two longevity proteins – survivin, specific for the protection and survival of epidermal stem cells and Sirtuin-1, for dermal cells. Key signaling proteins that impact the gap-junctions, epidermal-dermal junction and communication with fibroblasts and keratinocytes were shown to be boosted with in vitro testing. Ingenuity in analysis of the in vitro percentages of these longevity proteins yielded a “Youth Gain” of 11 years and strong positive results with in vivo clinical studies of furrows and various wrinkles.

Other Targets Beyond Aging
With a concept of targeting the causes and signs of skin sensitivity via cell communication, sederma’s mirabilis jalapa extract possesses the capacity to regulate the level of sensory receptors (TRPV1) and the signals between the epidermis and nerve endings. In vitro testing showed a significant decrease in the discomfort messenger Nerve Growth Factor and in vivo studies proved the ingredient to be effective with a reduction in itching and stinging sensation, reduced redness, and an improved feeling of comfort of sensitive and reactive skin.

In vitro testing demonstrates that cell-communicating ingredients can utilize known chemical pathways and receptors. By positively regulating skin functions, especially with the ability to reach the dermis via cell signaling, the visible signs of aging can be addressed with novel processes and perceptible results.

References:

1. Maibach, Howard I., Saqib J. Bashir, et al., (2002). Evidence-based Dermatology. Hamilton, Ont., B.C. Decker.
2. Srikanth R. Polusani, Rekha Kar, et al., (2011). Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR), Biochemical and Biophysical Research Communications.
3. Journal of Biological Chemistry, (2007), 22964-76; Seminars in Immunopathology, (2007), 15-26.
4. Journal of Investigative Dermatology, (2006), 2697-2706.
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6. Nature Medicine, (2003), 225-29.
7. Journal of Investigative Dermatology, (2002), 402-8;
8. International Journal of Biochemistry and Cell Biology, (2004), pages 1141-46;
9. Experimental Cell Research, March 2002, pages 130–137;
10. Skin Pharmacology and Applied Skin Physiology, (2002), 316-20.

Diahne Patnode, expert cosmetic chemist, has over 25 years of progressive experience in formulating and developing trendsetting cosmetic products for some of the most recognized names in the industry, including Redken Laboratories, philosophy/BioMedic, and Arbonne International. After studying biochemistry at the University of Arizona, she discovered the beauty industry and an insatiable curiosity for discovering the latest technological advances to create cutting-edge prestige products. As a leader in Research and Product Development, she continues to provide insight that delivers market leading products. Patnode holds multiple patents and is an active member of the Society of Cosmetic Chemists and Beauty Industry West.