J. Cosmet. Sci., 71, 321–350 (September/October 2020) 321 Current Topical Strategies for Skin-Aging and Infl ammaging Treatment: Science versus Fiction HEBA A. EASSA, MOHAMED A. ELTOKHY, HEBA A. FAYYAZ, MAHA K. A. KHALIFA, SEHAM SHAWKY, NADA A. HELAL, HADEER A. EASSA, SHAMS F. YOUSSEF, ISABEL K. LATZ, and MOHAMED ISMAIL NOUNOU , Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, AL-Azhar University, Cairo, 11651 Egypt (H.A.E., M.K.A.K., S.S.), Department of Microbiology, Faculty of Pharmacy, Misr International University, Cairo, 12598 Egypt (M.A.E.), Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt (H.A.F., S.F.Y.), Biomedical Engineering Department, College of Engineering, The University of Texas at El Paso, TX 79968 (N.A.H.), Genetic Engineering and Biotechnology Research Institute- University of Sadat City, 32958, Egypt (H.A.E.), Department of Public Health Sciences, College of Health Sciences, The University of Texas at El Paso, TX 79968 (I.K.L.), Department of Pharmaceutical Sciences, School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, Hartford, CT 06103 (M.I.N.) Accepted for publication May 12, 2020 Synopsis Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Infl ammaging has recently emerged as a pathway that correlates aging and age-related diseases with infl ammation. This review discusses the role and pathways of infl ammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with infl ammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier- based formulations. In recent years, consumers’ demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the effi cacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations. Address all correspondence to Mohamed Ismail Nounou at firstname.lastname@example.org.
JOURNAL OF COSMETIC SCIENCE 322 INTRODUCTION Biologists have defi ned aging as “age-dependent or age-progressive decline in intrinsic physiological function, leading to an increase in age-specifi c mortality rate (i.e., a decrease in survival rate) and a decrease in age-specifi c reproductive rate” (1). As we age, our skin becomes thinner, paler, and wrinkled with irregular pigmentation (2). Different clinical parameters are used for estimating apparent age such as under eye lines, forehead lines, crow’s feet, and age spot. Other biophysical parameters, such as skin texture, and fi rmness evaluation instrument and biochemical parameters (glycation and proliferation) are also used to determine apparent age (3). Being the most visible part, the skin receives our greatest attention and care, especially from women (4). Ancient civilizations have already aimed to control and prevent skin aging (5), such as ancient Egyptians who used sour milk baths, oils, and fruit acids for skin renewal or types of sandpaper to remove and smoothen scars (6). Nowadays, Americans’ expenditure on products for skin care amounts to around $43 billion/year (4). This con- tinued interest fueled research into skin-aging processes and treatments. First introduced by Giacomoni and D’Alessio as a model to describe skin aging (7), in- fl ammaging is a fi eld of research that was imagined by Franceschi et al. (8) to extend the study of the role of infl ammation in the aging of different organs, and age-related dis- eases and processes, including skin aging (8). It differs from infl ammation, which is a natural body response to injury, infection, or trauma. Infl ammation is a complicated process which facilitates source removal and tissue repair based on the release of proin- fl ammatory mediators and cells, such as neutrophils, macrophages, and monocytes, until it reaches a resolved state (hemostasis) (9). However, if the stimulus is low grade and persistent, a chronic, nonresolving infl ammation (infl ammaging) will occur (10). There is a strong, but complex, correlation between infl ammaging and age-related disease, in- cluding skin aging. This review focuses on the mechanisms of infl ammaging that lead to skin aging. Moreover, strategies and topical approaches for skin-aging treatments are discussed. Immune cells in the dermis release singlet oxygen and matrix metalloproteinases (MMPs), causing connective tissue damage. During this immune response, other cells are damaged, releasing proinfl ammatory mediators and repeating the cycle (11). The microinfl amma- tory theory could explain a number of skin-aging features such as loss of elasticity, and dermal fl exibility. Moreover, this theory accounts for wrinkle appearance and epidermal thinning with age (12). Bhattacharyya et al. (13) assessed the histological changes in in- trinsic aged mice. Results showed that there was a notable epidermal thinning and reduc- tion in the pilosebaceous unit associated with aging (13). In addition, DNA damage plays a critical role in skin aging and can be caused by endogenous and exogenous factors. Endogenous agents are mainly reactive-oxygen species (ROS) resulting from different metabolic processes, while exogenous agents include UV radiation and chemicals (14). TYPES OF SKIN AGING Similar to other organs, skin aging is considered a progressive multifactorial process (15,16) based on a gradual decline in physiological integrity and cellular functions (15). It is often classifi ed as intrinsic or extrinsic aging (2).
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