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).

SKIN-AGING AND INFLAMMAGING TREATMENT 323 INTRINSIC AGING Intrinsic aging represents the inevitable and genetically determined aging of all tissues (17). It is shaped by endogenous physiological determinants, including gender, ethnicity, anatomical differences, and hormonal fl uctuations (18). Clinical signs of intrinsic skin aging include xerosis, fi ne lines, decreased elasticity, and subepidermal atrophy (17). These changes are based on reduced cellular proliferative capacity and genetic abnormalities (19). In addition, the dermis of older skin is characterized by fewer mast cells, fi broblasts, elastic fi bers, and lower amounts of collagen compared with younger skin (20). Moreover, signs of intrinsic skin aging not only include declines in fi brous extracellular matrix components, such as elastin, fi brillin, and collagens but also degeneration of oligosaccharides, which infl uence the skin’s capacity to preserve bound water (21). Although these structural changes are natural aspects of skin aging, environmental and individual factors, such as UV exposure and diet, can dramatically infl uence the rate of skin aging (22). EXTRINSIC AGING Extrinsic aging is referred to as photoaging, as it is shaped by environmental causes, es- pecially UV exposure (22). In fact, UV radiation exposure is considered the key determi- nant of extrinsic skin aging and attributable to 80% of facial skin aging (2). Whereas intrinsic aging causes epidermal thinning, photoaging is characterized by epidermal thickening based on impaired keratinocyte differentiation in the epidermal layer and basal cells (23). In addition, keratinocyte proliferation is impaired in both stratum cor- neum (SC) and basal cells (24). Furthermore, accelerated skin aging is associated with increased levels of MMPs (an enzyme family responsible for the decay of collagen and extracellular matrix proteins) (25). Although elastic fi ber degradation is a characteristic feature associated with aging, pho- toaging exhibits enormous accumulation of dystrophic elastin in the dermis known as solar elastosis (26). Elastin degradation in photoaging could be due to MMP activation, specifi cally human macrophage metalloelastase secreted by keratinocytes, fi broblasts, and infl ammatory cells (27). Mora Huertasa et al. (28) investigated the molecular changes in elastin associated with normal aging and photoaging. The study revealed that the elastin cleavage pattern is different in both types and is more pronounced in photoaging. More- over, the N-terminal of tropoelastin becomes more susceptible to enzymatic degradation due to photoaging (28). Moreover, air pollution has detrimental effects on skin. Air pollutants (ozone, volatile organic compounds, oxides, and others) alter skin homeostasis and induce aging and other infl ammatory diseases. This infl uence could be attributed to different mechanisms includ- ing free radical production, infl ammatory mediator release, and skin barrier damage (29). MOLECULAR PATHWAYS AND PROCESSES OF SKIN INFLAMMAGING It is important to identify molecular mechanisms, which are likely complementary and interconnected, that control skin aging to fi nd benefi cial approaches for prevention and treatment. Infl ammaging plays a crucial role in age-related diseases, such as osteoporosis,