Due to improved living conditions and high medical standards, the proportion of elderly is continuously increasing in the population of industrial countries [1]. Aging impairs the function of many cells and tissues and thus favors the development of various diseases. In order to attenuate the aging-related increase in morbidity and to enable healthy aging, a deep understanding of the molecular mechanisms of aging is mandatory. In addition to intrinsic or chronological aging, which is largely genetically determined, exposure to exogenous stress factors may accelerate the aging process [2,3]. This is particularly evident in the skin, which is constantly exposed to a variety of environmental, occupational and lifestyle factors that can accelerate the development of the clinical signs of extrinsic skin ageing, i.e. coarse wrinkles and pigment irregularities [2,4]. Given that in addition to age, the skin projects social status, wealth, sexuality, and other socially important attributes, its accelerated decline may seriously affect self-confidence and quality of life [5,6]. The totality of non-genetic factors and their interactions that drive extrinsic skin aging is defined as the skin aging exposome [7]. In addition to ultraviolet (UV) radiation [2] and tobacco smoke [8], exposure to particulate air pollution (PM), which according to the US Environmental Protection Agency, is one of the criteria pollutants that affect human health even at low concentrations [9], contributes to extrinsic skin aging.

Airborne PM is emitted by various anthropogenic and natural sources and further categorized according to its aerodynamic diameter, e.g. PM10 and PM2.5 for particles with a diameter of equal or less than 10 μm and 2.5 μm, respectively. PM2.5 is emitted by vehicular traffic, residential wood and coal burning, cooking, wildfires, and other combustion processes, and serves as carrier for various transition metals, salts, bacterial endotoxins, and organic chemicals, especially polycyclic aromatic hydrocarbons (PAHs) [[10], [11], [12]]. An overview about the ten most abundant PAHs present in samples of urban dust, urban PM and diesel PM, which are all available as Standard Reference Material (SRM) at the Nationally Institute of Standards and Technology (NIST; www.nist.gov), is given in Table 1.

In contrast to the prevailing assumption that fine PM is primarily absorbed via the respiratory tract, several studies indicate that the skin also serves as a relevant entry site for PAH-rich PM [13]. In fact, dermal absorption has been identified as the most important pathway for the uptake of PAHs and PAH-rich PM from barbecue fumes [14,15]. Accordingly, ambient PM efficiently penetrates reconstructed human epidermis [16]. Moreover, topical application of PM induces inflammatory responses and disturbs proper keratinocyte differentiation in 3D full thickness models, epidermal equivalents [[17], [18], [19]] and human skin explants [20]. Hence, upon repetitive or chronic exposure, dermal penetration rates of airborne PM may increase due to a progressive impairment of the epidermal barrier. Studies investigating occupational PAH exposure routes [[21], [22], [23], [24]] found out that dermal exposure has an equal or even greater impact on systemic PAH levels than inhalation, and these findings are further strengthened by a considerable number of experimental PAH penetration studies [19,25,26]. The reason for this could be the relatively high fat content of the skin rendering it easy to access for lipophilic pollutants [27].

Studies assessing the impact of diesel exhaust particles (DEP) and extracts derived thereof on human bronchial epithelial cells and macrophages revealed that the organic PAH-rich fraction is of utmost relevance for the induction of pro-inflammatory responses via the aryl hydrocarbon receptor (AHR) [[28], [29], [30], [31], [32]]. In its resting state, AHR is part of a cytosolic multiprotein complex consisting of a heat-shock protein 90 dimer, AHR-interacting protein, co-chaperone p23 and soluble tyrosine kinase c-Src (Fig. 1) [33,34]. Upon binding of a ligand, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or benzo[a]pyrene (BaP), the AHR protein undergoes conformational changes leading to the dissociation of the multiprotein complex and the nuclear translocation of AHR. In the nucleus, AHR heterodimerizes with ARNT and binds to xenobiotic-responsive elements (XREs) in the enhancer region of genes to induce their transcription. Target genes that are frequently used to proof potential AHR activation encode for xenobiotic-metabolizing enzymes, in particular for cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1 [33,34]. In the presence of NADPH, these monooxygenases reduce molecular oxygen to incorporate one oxygen atom into the substrate, i.e. the invading AHR-activating compound, while the second is converted to water. This increase in the polarity of the substrate enable its conjugation with water soluble moieties and thus its detoxification. However, as discussed later on, highly reactive metabolites generated during this process may disturb the cellular integrity [35].

In addition to the canonical signaling pathway, the AHR ligand-mediated dissociation of the cytosolic multiprotein complex leads to the release of c-Src, which subsequently activates epidermal growth factor receptor (EGFR) and downstream signal transduction resulting in the transcriptional upregulation of XRE-independent genes (Fig. 1), for instance encoding aldo-keto reductase (AKR) 1 isoforms [36].

In this article we focus on the critical role of AHR signaling pathways and their impact on oxidative stress and pro-inflammatory responses in the context of airborne PM exposure-triggered extrinsic skin aging. According to the concept of oxinflammation [37,38], we postulate that oxidative stress and mild inflammation reinforce each other in a vicious cycle, ultimately causing tissue damage and functional decline. We start with a brief overview on population-based studies linking airborne PM exposure to skin aging. Afterwards, we focus on redox-related processes and pro-inflammatory responses which may foster the development of pigment spots and wrinkles. We close by briefly reviewing the potential interactions between particulate air pollution and solar UV radiation, another factor of the skin aging exposome known to modulate AHR activity [39].