134 JOURNAL OF COSMETIC SCIENCE THE INS AND OUTS OF SKIN PROTECTION TECHNOLOGIES Daniel Maes, Ph.D., D. Collins, H. Corstjens, Ph.D., L. Declercq, Ph.D., R. Foyouzi-Youssefi, Ph.D., D. Gan, L. Hellemans, Ph.D., M. Ingrassia, T. Mammone, Ph.D., M. Matsui, Ph.D., E. Pelle, Ph.D. and I. Sente Estee Lauder Companies, Inc., 12 5 Pine/awn Road, Melville, NY 117 4 7 It is now well accepted that most of the visible signs of aging which appear on the face, are caused by the various factors we are exposed to on a continual basis. As Cosmetic Scientists, we used to believe that most if not all of this damage, visible in the form of lines and wrinkles, abnonnal skin pigmentation, and skin sagginess, were the clinical manifestations of damage resulting from an excessive exposure to the sun. However, it has now become obvious that exposure to solar ultraviolet (UV) and infrared (IR) rays is only partly responsible for the progression of cutaneous damage. Recent evidence suggests that other factors such as smoke from cigarettes, industrial pollution, Ozone which accumulates during the day at ground level, irritants and sensitizers which we get in contact with, and even the psychological stress which we endure in our daily lives play an important role in promoting additional damages to the skin. Clearly, from such an exhaustive list of challenges, it seems likely that the more classical way of protecting the skin with chemical sunscreens will not suffice. Indeed they have the great merit to reduce significantly for some time the damages caused by UVB and UV A to essential bio-molecules, such as DNA lesions as well as oxidized proteins and lipids. But oYer the past 15 years substantial progress has been made by marrying the effect of sunscreens with the activity of topical antioxidants, in order to provide broader and longer lasting protection benefits. During that time period, a few long-term clinical studies have demonstrated tl1e benefits one can expect from the regular treatment of the skin with such molecules. They do however present some challenges to the formulator, as their lack of stability in an emulsion, obviously due to their antioxidant activity, limits sometimes tl1eir usage to low concentrations that do not allow for the complete control of the oxidative damage taking place in the skin. As a consequence, a fairly complex and devastating cascade of events is taking place: First, tl1e oxidafo·e damage to the cell membrane will induce the release of proinflammatory mediators that will ultimately lead to the activation of metalloproteases, capable of gradually degrading the extracellular matrix. The end result will be a loss of integrity, firmness and elasticity of the skin. A second, even more dreadful impact of the oxidative damage to our cells is certainly linked to protein oxidation. Indeed, this process will not only affect the function of essential structural proteins such as collagen, elastin and keratins, but in addition it can lead to a loss of activity for key enzymes in our skin. Such deactivation can have an impact at various levels. It can affect barrier integrity by perturbing the cellular desquamation process, since the stratum comeum chymotriptic enzyme (SCCE) is susceptible to UV-induced oxidative deactivation. It can also compromise the internal antioxidant defense mechanism since catalase, responsible for the reduction of hydrogen peroxide into water, is known to be deactivated by UVA exposure. More recent developments in technology allow us to compensate for such deactivation of the cells' own ability to protect tl1emselves from these oxidative damages. Specific molecules have been synthesized or extracted from plants to reactivate the deficient antioxidant mechanism such as N-Acetyl-Cysteine to replenish the pool of intra-cellular glutathione, or the UVA stable catalase mimetic EUK-134 (Fig. 1), to compensate for the UVA-induced loss of catalase activity.

2003 ANNUAL SCIENTIFIC MEETING 120 100 .C' · 80 ·.::, ;;l � 60 :1 40 � 20 0 0J/cm2 2J/cm2 6J/cm2 12J/cm2 UVA dose Fig. I: Effect of UV A exposure on the in vitro catalase activity of EUK-134 (Eukarion, Inc) and catalase from bovine liver (Sigma) Another interesting avenue for the enhancement of the cellular protection mechanisms is to induce the expression of various Heat Shock Proteins which have the properties not only to protect specific UV sensitive enzymes such as catalase, but have been shown to refold the proper terti ary structure of damaged proteins, resulting in a restoration of the activity. Finally, increasing the cell's own energy reserve via topical application of Creatine has been shown to enhance cellular protection mechanisms in UV exposed skin cells, resulting in a significant reduction of both mitochondrial and nuclear DNA damage as well as a reduction of sunburn cell formation. These results clearly demonstrate the relevance of increasing the overall cellular metabolism to improve the overall defense capacity against the oxidative stress generated by exposure to the environment Conclusion These observations strongly support the need for development of a multi-branched technology to provide the necessary protection to cells exposed to the oxidative damages generated by an environment which has evolved dramatically over the last 100 years and which is creating a significant burden to mammalian cells. The development of an optimal protection technology cannot be based exclusively on a simple combination of efficacious sunscreens alone, but should provide a well balanced combination of sunscreens, antioxidants, anti-inflammatory agents, together with ingredients that will enhance the cells' own ability to protect themselves from various environmental insults. We do believe that the cosmetic industry is playing an important role in providing consumers with the best protection available today, as clearly mammaJian cells have not been able to adapt their protective mechanisms to the additional oxidative stress which results from the increase in environmental pollution all over the world. 135