When reviewing marketing claims or new ingredients, general cell biology and biochemistry allows you to manage the scientific facts. What’s key to note is that cellular processes in skin cells haven’t just suddenly developed new talents. All of these processes in the cell have been going on for millions of years. The biochemistry of the cell should always be the benchmark for ingredient science.
So how should topical ingredients relate to the functioning of the cell?

Cellular and Intercellular Components
All cells are surrounded by a cell membrane. The cell membrane keeps the components of the cell isolated from the external environment. It also serves as the communications interface between the cell and its environment. Biological membranes also compartmentalize cellular functions.
Cell membranes contain various types of lipids, the specific composition of which is important for maintaining membrane fluidity. These lipids have a charged, hydrophilic (water loving) portion of the molecule on the outside of the membrane and a lipophilic (lipid loving) portion sandwiched in between. Contained within cell membranes are also proteins and peptides vital to the cell.
Having ingredients imitate the structure of the biomembrane should be the backbone of every moisturizer or hydrator for your client. Intercellular substances are those ingredients that exist naturally in skin, and that work to hold skin cells together. An arid or dry environment, photoaging, irritation, inflammation, and general intrinsic aging can all greatly reduce the presence of these natural substances in skin. Ingredients such as ceramides, fatty acids (linoleic acid, triglycerides, glycerin, phospholipids, and lecithin), and glycosaminoglycans (hyaluronic acid) are essential for helping skin function normally. These ingredients can help keep cells and the substances between cells stay hydrated to maintain health longer, as well as improve the skin surface.
Ceramide and Fatty Acids have an important role in the barrier properties of the cell membrane and therefore the skin. Not only do they limit the loss of water, in addition, they prevent the ingress of harmful substances. Linoleic Acid, Squalane, and Shea lipids, for example, can protect against environmental degradation in addition to having anti-inflammatory and "cell renewal" properties.
Glycosaminoglycans or GAGs are a family of proteoglycans and are located in the intercellular matrix of the dermal connective tissue. The biological functions of proteoglycans include the regulation of cell growth, cell signaling, inflammation, and interactions with growth factors and their receptors. GAGs promote the ability of collagen fibers to retain water and bind moisture into the stratum corneum of the epidermis. The most important GAG in the skin is Hyaluronic Acid (HA). HA is able to bind up to 1000 times its weight in water and acts like a moisture magnet to maintain extra cellular fluidity. The skin contains over 70 percent water and renews it more readily than most other bodily tissues. HA is absolutely vital to its structure and daily maintenance.
Cells also have a set of 'little organs', called organelles that are adapted and/or specialized for carrying out one or more vital functions. The most notable is the cell nucleus, as it is the place where almost all DNA replication and RNA synthesis occur. The nucleus is separated from the cytoplasm, the fluid inside the cell, by a double membrane called the nuclear envelope. The nuclear envelope isolates and protects a cell's DNA from various molecules that could accidentally damage its structure or interfere with its processing. During processing, DNA is transcribed, or copied into a special ‘messenger’ RNA, called mRNA. This mRNA is then transported out of the nucleus into the cytoplasm, where it is translated into a specific protein or peptide molecule.
Within the cytoplasm is another organelle, the mitochondria. Mitochondria have their own DNA and are self-replicating. They are the 'power plants' of the cells: They convert chemical energy stored as sugars, amino acids, and fatty acids into Adenosine Triphosphate (ATP) that the cell can use to maintain its structure and to grow and reproduce. This ‘power plant’ consumes approximately 85 percent of the oxygen, and because of this high oxygen use, the mitochondria unfortunately also have the highest production of harmful oxygen free radicals.
Any free radical involving oxygen is referred to as Reactive Oxygen Species (ROS). These free radicals contain two unpaired electrons in the outer shell. When free radicals steal an electron from a surrounding compound or molecule a new free radical is formed in its place. In turn the newly formed radical then looks to return to its ground state by stealing electrons from cellular structures or molecules. Thus, the destructive chain reaction begins. ROS damage cellular DNA, lipids, and protein. Cellular energy deficits caused by declines in mitochondrial function by ROS can also impair normal cellular activities and compromise the cell's ability to adapt to various physiological stresses, a major factor in aging. Oxidative damage to mitochondrial lipids also contributes to the decreasing fluidity of cell membranes. Other effects of ROS include a relatively high rate of mitochondrial DNA mutation.
Mitochondria do contain natural enzymes capable of protecting against the deleterious effects of ROS. These include Superoxide Dismutase, Co-enzyme Q10, and Lipoic Acid. Superoxide Dismutase (SOD) is arguably the body’s most crucial antioxidant, as it is responsible for disarming the most dangerous free radicals of all: The highly reactive superoxide radicals.
Lipoic Acid is an antioxidant that has been shown to not only reverse the age-related decrease in oxygen consumption and restore the age-related decline in mitochondrial membrane potential, but also significantly lower the age and environmentally related increase in ROS oxygen radicals.
Co-enzyme Q10 or CoQ10, also known as ubiquinone, is a fat-soluble antioxidant that helps to protect the lipid membranes of the cell from free radical attack, as well as being essential in vitamin E regeneration.
These protective substances and mechanisms, however, do decrease with age. In addition, increased environmental stress, toxins, etc., generally limit our cells' ability to combat free radicals and eliminate oxidative stress. The additional topical application of these natural cell protectants, therefore, is essential for optimal cell activity.

Biochemical Cell Communication
All living cells sense and respond to their environment by a set of mechanisms known as cell signaling – part of a complex system of communication that governs basic cellular activities and coordinates cell actions. Specific chemicals mediate cell-to-cell communication in the skin between keratinocytes, fibroblasts, and other cell types present in the skin to enhance cellular activity. As a result, anti-aging and skin normalizing benefits can be achieved through many ‘cell signaling’ active ingredients.
Ceramides in the stratum corneum, primarily known for their ‘barrier’ role, main biological function is in cellular signaling, especially in how skin cells grow and differentiate – a process through which skin cells become specialized. Ceramide ingredients such as the botanical Ceramide 2 and Ceramide 3 can help communicate messages to these skin cells that let them know how they should be ‘acting’.
Melasma or Melanogenesis is another form of cell communication between keratinocytes and melanocytes. Melanin is synthesized in melanocytes, which are normally found in the epidermal basal layer. Melanocytes deposit melanin via cellular extensions called dendrites that reach out to other cells in the epidermis. Within the melanocytes, melanin is bound to a protein matrix to form melanosomes. In the melanosomes, tyrosinase is an essential enzyme in the biosynthesis of melanin. Tyrosinase inhibitor ingredients act upon the cell by inhibiting or ‘turning off’ the production of melanin by melanocytes. By blocking the various points of the pathways, natural skin brightening agents can inhibit or even reverse melanin biosynthesis and are thus useful in the treatment of hyperpigmentation or spots that are caused by local increase in melanin synthesis or uneven distribution. These include Licorice Extract (Glycyrrhiza Glabra), Bearberry Extract (Arctostaphylos Uva-Ursi), Arbutin, Kojic Acid, Azaleic Acid, and Ellagic Acid.

Cell Stress and Inflammatory Responses
Stress is one of the major characteristics of our modern life, and much data has shown that stress has a direct effect on skin health and appearance. Remember, skin is the body's first line of defense against aggressions from the environment.
Free radicals (particularly from UV radiation) attack the structure of cell membranes, which then create metabolic waste products. Such toxic accumulations interfere with cell communication, disturb DNA, protein synthesis, lower energy levels, and generally impede vital cell biochemical processes. Free radicals can be transformed and stabilized, however, by free radical scavengers – otherwise known as antioxidants. The term antioxidant means "against oxidation." Antioxidants are effective because they are willing to give up their own electrons to free radicals. When a free radical gains the electron from an antioxidant, it no longer needs to attack the cell and the chain reaction of oxidation is broken. After donating an electron, an antioxidant becomes a free radical by definition. Antioxidants in this state are not harmful because they have the ability to accommodate the change in electrons without becoming reactive.
There are two lines of antioxidant defense within the cell. The first line, found in the fat-soluble cell membrane consists of vitamin E, ß -Carotene, and Co-enzyme Q10. Of these, vitamin E is considered the most potent chain breaking antioxidant within the membrane of the cell. Because it is lipid soluble, it is particularly suited for preventing lipid peroxidation, the destruction of the lipids in the cell membrane. By donating a hydrogen ion, vitamin E (Tocopherol) reduces the peroxyl radical to a harmless oxidized lipid breaking the steps that would otherwise initiate lipid peroxidation.
Cells also contain numerous nonenzymatic antioxidants including vitamin C (Ascorbic Acid), vitamin A, (ß-Carotene), and Glutathione (GSH). The natural antioxidant vitamin C does more than inhibit skin-damaging free radical activity. It is also required for collagen synthesis, which declines markedly in aging skin. As humans age, they suffer diminished microcapillary circulation within the skin, thereby depriving skin cells of the supply of vitamin C it needs for youthful collagen synthesis. The topical application of vitamin C in a skin-penetrating medium can enhance the availability of vitamin C for collagen production. Vitamin C regenerates vitamin E and enables vitamin E to provide sustained antioxidant protection in the skin's elastin fibers. Vitamin C also plays a vital role in skin repair. When skin is injured, its vitamin C content is used up rapidly in the scavenging of free radicals, and in synthesizing collagen to speed healing.
Of course, the first protection to the cell from the excess of environmental assaults is a broad UVA and UVB spectrum sunscreen against the generation of free radicals caused by sun exposure. This prevents a substantial amount of free radical damage before it can even start; but because free radicals come in a hierarchy (according to their potential for damage) with the hydroxyl-radical and superoxide-radical at the top of the list, your client needs a cross-section of antioxidants for the cascade effect in converting into lower damage free radicals, not a one-ingredient-fits-all approach. This includes the natural ingredients of vitamins A, C, and E, in addition to bioflavonoids. These compounds work synergistically to neutralize free radicals formed by UV exposure. In addition, Alpha Lipoic Acid can regenerate both vitamin E and C nutrients to extend their effectiveness.

The Ultimate Goal: Enhancing Cell Longevity
Understanding the molecular basis of cellular function provides insight into not only ingredient function and activity, but in the effective anti-aging treatment of your clients. Aging is a loss of equilibrium between the capability of a cell to maintain its repair potential and the frequency and intensity of the damages to which it is exposed. For the skin, the most exposed organ to environmental insults, free radicals generated by ultraviolet radiation and internal metabolism are considered to be the most important deleterious aging agents on cellular proteins, lipids, glycans, and DNA. Cell protecting anti-aging ingredients for now and into the near future therefore must:

1. Contain natural cell free-radical scavengers or technologies focusing on active ingredients which, along with attacking free radicals directly, must also reinforce the natural cellular components and organelles that detoxify these free radicals
2. Protect the organelles and structures of cellular proteins and lipids
3. Affect the life span of the cell and improve stress resistance by controlling key metabolisms and cell-signaling pathways

Effective and active products, therefore, must highlight basic cell science as the backbone of new and effective ingredients and treatments.

Kimberly J. Heathman has been in the professional and retail skin care industry for more than 25 years, including extensive leadership experience in retail, cosmetics brand and product development, senior level project management with Nordstrom Inc., and such major cosmetic firms as the Estee Lauder Companies Inc. Heathman holds a B.S. in Chemistry and Biology; is a member of the Society of Cosmetic Chemists and The Biochemical Society; and is an educator and published author in Ingredient Chemistry and Skin Care Biochemistry. Heathman is the Executive Vice President-Director of Strategic Marketing and Business Development at GlyMed Plus / Advanced Aesthetics Inc. For more information, please visit www.glymedplus.com.