J. Cosmet. Sci., 64, 455–468 (November/December 2013) 455 Use of small RNA as antiaging cosmeceuticals PINGJING ZHANG, JIANXIN CHEN, TIEJUN LI, and YORK YUANYUAN ZHU, Biomics Biotechnologies Co. Ltd, Economic & Technology Development Area, Jiangsu, The People’s Republic of China 226016, and Small RNA Technology and Application Institute, Nantong University, Economic & Technology Development Area, Jiangsu, The People’s Republic of China 226016. Accepted for publication May 17, 2013. Synopsis Over the past two decades, RNA interference (RNAi) has achieved great improvements in medicine, which has benefi ted the development of innovative cosmeceutical products, particular, to antiaging cosmeceuticals. A variety of ongoing research has tried to employ small RNAs—small interference RNA and microRNA as new cosmeceutical ingredients. Furthermore, several skin care companies have released new small RNA products in cosmetic market. In this review, we will describe the latest and most advanced approaches and strategies of using small RNA as antiaging cosmetics, including investigations on aging-related genes that small RNA target, method of delivering them, and challenges in the development of RNAi-based therapeu- tics for skin care cosmeceuticals. It is certain that advancement in this direction will evolve a new landscape for innovative antiaging cosmeceuticals. INTRODUCTION Modern society is increasingly integrated across national borders, and the global economy has augmented consumer access and individual buying power exponentially. In addition, advances in medicine have led to a trend of increasing life expectancy. The combination of these factors has resulted in the establishment and growth of the personal care market (1). Dr. Albert Kligman originally coined the term cosmeceutical and defi ned it in 1984 as a formulation that is used to improve the appearance of skin, but not for therapeutic purposes (2). Today, cosmeceuticals have become the fastest growing sector of personal care industry (3). Skin care companies have been continuously releasing new and innova- tive products that promise to transform the appearance of aging skin (4). A number of topical cosmeceutical treatments for conditions such as photoaging, hyperpigmentation, wrinkles, and hair loss have come into widespread use (5). Over the past two decades, advancement in cosmeceuticals has generated a variety of strategies for antiaging treatment, including applications of recombinant proteins, peptides, Address all correspondence to Pingjing Zhang at frank@biomics.cn.

JOURNAL OF COSMETIC SCIENCE 456 natural bioactive compounds, herbal products, and many others (6). More recently, devel- opment in new cosmeceutical products has benefi ted from applications of newly advanced technologies such as RNA interference (RNAi). Today, a great deal of antiaging research has focused on the use of small RNA for improved appearance of aging skin as well as against hair loss (7). In this review, we will focus on recent progress in research and devel- opment of using small RNA in antiaging cosmetics, including investigations on aging- related genes that small RNA target, method of delivering them, and challenges in the development of RNAi-based therapeutics for skin care cosmeceuticals. CHARACTERISTICS OF AGING Skin aging is a complex biological phenomenon consisting of two components aging caused by the genes we inherit is called intrinsic aging, the other type of aging is known as extrinsic aging and is caused by environmental factors. The process of intrinsic skin aging is thought to involve decreased proliferative capacity leading to cellular senescence and altered biosynthetic activity of skin-derived cells (8). Extrinsic aging, more com- monly termed as photoaging, also involves changes in cellular biosynthetic activity but leads to gross disorganization of dermal matrix. With advancing age, the dermal/epider- mal junction becomes relatively fl at resulting from retraction of the epidermal papillae as well as microprojections of basal cells into the dermis. This fl attening results in a more fragile epidermal/dermal interface and, consequently, the epidermis is less resistant to shearing forces. The three-dimensional arrangements of collagen and elastic fi bers show marked alterations with age. Both fi brous components appear more compact because of a decrease in spaces between the fi bers. Collagen bundles appear to unravel, and the indi- vidual elastic fi bers show signs of elastosis (9). Skin aging leaves visible signs on the surface of skin and physical properties of the skin are modifi ed. The most obvious clinical impression of elderly skin comes from increased formation of wrinkles and defi cits in elasticity, another evidence of increasing age includes irregular dryness, dark/light pig- mentation, sallowness, severe atrophy, telangiectases, premalignant lesions, laxity, and leathery appearance (10). Functional changes in the skin of elderly persons include a de- creased growth rate of epidermis and hair (11). Both intrinsic and extrinsic factors may conspire to hair aging. Intrinsic factors are related to individual genetic and epigenetic mechanisms with individual variations, whereas extrinsic factors include ultraviolet (UV) radiation, air pollution, smoking, and nutrition (12). Extrinsic factors insults to the fi ber that induce hair weathering and fraying (13). The aging of follicles caused by intrinsic factors manifests as de- crease of melanocyte function (graying) and decrease in hair production (alopecia) (14). MECHANISM OF RNA INTERFERENCE In the late 1990s, a landmark study demonstrated that gene expression could be inhib- ited by an introduction of double-stranded RNA with a sequence complementary to the gene being targeted, a mechanism that was referred to as RNAi (15). The importance of this work was well recognized by the 2006 Nobel Prize in physiology or medicine.