Pollution is defined as an environmental contamination by chemical, biological, or physical substances which can affect human health and ecosystems. Air pollutants are composed of organic and inorganic substances which are introduced into the atmosphere by residential wood heating, tobacco smoking, transportation, and industry, among other sources ^[1][78]. The composition of atmospheric pollution can also vary depending on the time of day, seasons, human activity, and geographic location ^[2][3][8,9]. Several reports suggest that air pollutant components are direct contributors to the process of aging ^{[4][5][6][7][8][9]}[5,11,79,80,81,82]. Human exposition to air pollution contributes to increased mortality and hospital stays. The effects of air pollution can range from nausea, difficulty in breathing, skin irritation, birth defects, and reduced activity of immune system, to cancer. Results obtained from research with animal models and epidemiological studies suggest that the cardiovascular and respiratory system are the main affected systems by air pollution [10]. In the lungs, infiltration of air pollutant components, especially small particles which can reach bronchial tubes and deep lung, can induce a systemic immune response due to increased expression of IL-1, IL-6, IL-8, and monocyte chemoattractant protein-1 in macrophages and lung epithelial cells, leading to the development of respiratory diseases ^[4][5].

The skin can be affected by air pollution in two ways. Either directly, through the uptake of the air pollutants by the skin, especially by intrusions formed by hair follicles in the stratum corneum ^[4][5], or indirectly by the uptake of particles by the lungs which are further transported by the blood to the skin ^[3][9]. Exposure of the skin to urban air pollution activates mechanisms of cell detoxification, which, if active over a longer period of time, can lead to DNA and protein damage, elevated ROS levels and lipid peroxidation, resulting in skin alterations, such as impaired barrier function, pigment spots, wrinkles, and decreased skin hydration ^[11][12][83,84]. Additionally, air pollution induces inflammation, activates the AhR pathway, and leads to alterations of the skin microbiome ^[13][14][85,86]. Given the strong link between low-grade systemic inflammation and biological aging, it is possible that exposition of the skin to air pollution leads to premature cellular senescence and, consequently, to skin aging ^[13][85]. The literature regarding the effects of air pollution on different ethnic skin types is still elusive. The few broad ethnic studies show that exposition of the skin to air pollution mainly induces increased oxidative stress leading to skin pigmentation disorders and wrinkle formation ^[5][15][16][2,11,72]. Information on the effects of air pollution on different skin types is still lacking and therefore the awareness of different ethnicities in this field of research needs more attention.

Particulate matter (PM) is one of the main components of air pollution and is defined as a mixture of gas containing liquid and/or solid droplets varying in size and composition ^[14][17][86,88]. Particles contained in PM include substances such as metals, minerals, organic toxins, tobacco smoke, pollen, allergens, and smog ^[18][89]. These particles are classified according to their aerodynamic diameter (Dp) in three categories: particles with Dp bellow 10 µm are named “coarse particles” or PM 10 and include components of dust, soil, and dusty emission from industries; particles with Dp between 0.1 and 2.5 µm are called “particle matter” or PM 2.5 and are mainly derived from open fires, automobile exhausts, and power plants ^[19][90]; and particles with Dp bellow 0.1 µm are called “ultrafine particles” or PM 0.1 and mainly consist of emissions of diesel-powered engines ^[14][86]. The aerodynamic diameter of the particles is an important determinator of their ability to enter the body by alveolar–capillary barrier and travel across the blood ^[20][91]. The particle matter and ultrafine particles can penetrate the body either by systemic distribution through the blood circulation after entering the lungs’ alveoli or by infiltrating the skin through hair follicles ^[21][92]. Recently, in contrast with what was believed before, it was demonstrated that coarse particles can also penetrate the stratum corneum or the respiratory system ^[22][23][53,93].

Exposure to particulate matter can cause cardiovascular and respiratory diseases, allergies, and cancer through different mechanisms ^[11][24][83,94]. For instance, PM 2.5 exposure induces endoplasmatic reticulum stress response and apoptosis in the lung and liver of mice and this mechanism is believed to be one possible explanation for the development of metabolic, respiratory, and cardiovascular diseases in humans exposed to air pollution ^[25][95]. A study in mice showed that PM inhalation activates the TNF-α driven systemic inflammation and results in an impaired cardiac function which to a certain extent was prevented by a TNF-α inhibitor called inflimiximab ^[26][96]. In skin diseases such as psoriasis, the blockage of TNF-α leads to detrimental side-effects such as increased risk of infections and malignancies as well as to the formation of new and more psoriatic skin lesions ^[27][97].

A cross-sectional study which investigated the correlation of particulate matter exposure and aging demonstrated that leukocytes of peripheral blood from elderly humans exposed to daily high concentrations of PM 2.5 presented decreased telomere length, lower mitochondrial DNA content, and reduced sirtuin-1 expression ^[28][98]. In another study it was shown that exposure of human nasal epithelial cells to PM 2.5 leads to ROS production, degradation of tight junction proteins such as occludin, claudin-1, and E-cadherin, leading to sinonasal diseases through disrupted tissue integrity and permeability ^[29][30][45,99]. Similar downregulation of tight junctions as well as keratins and filaggrin were observed in pork skin in response to PM 2.5 exposure, leading to increased skin permeability ^[31][32][100,101]. Altogether, these studies demonstrate that short- and long-term exposure to PM can induce features of premature aging.

Particularly in the skin, PM 2.5 induces different detrimental processes such as DNA damage and lipid peroxidation. Exposure of the skin to PM results in the formation of senile lentigines, increased formation of ROS, and promotes the release of pro- inflammatory cytokines which all lead to accelerated skin aging and increased susceptibility to pathogen invasion ^[4][5]. ROS generation, induced by exposure of the skin to air pollution, can induce MMPs expression and increase their activity, especially MMP-1 and MMP-3 which are known to accelerate the skin aging process by degrading collagen and elastin. Additionally, the decreased expression of transforming growth factor (TGF) β, and reduced synthesis of collagen type 1 α chain (COL1A1, COL1A2) and elastin by fibroblasts are other contributors to the formation of wrinkles and skin aging induced by PM ^[7][9][33][80,82,102].

In human keratinocytes and mouse skin tissue, PM induced the expression of demethylases such as DNA demethylase 1 (TET1) and decreased the expression of DNA methylation-related proteins such as (DNMT)-1 and -3. These changes in the methylation pattern of DNA induced “skin senescence phenomenon” are characterized by features such as hyperkeratotic epidermis accompanied by the increased expression of keratin-10, an epidermal differentiation marker, and proliferating cell nuclear antigen, a proliferation marker ^[6][79]. These results demonstrate that PM-induced skin aging can be triggered by epigenetic modifications which could give rise to new strategies for therapeutics against skin aging.

Skin cells exposed to diesel particulate extract (DPE), which mainly contains PM and PAH ^[34][103], displayed dysregulation of proteins and lipids important for the maintenance of skin integrity, for the regulation of skin hydration and oxidative stress, such as NADPH oxidase (NOX), ceramide, plakins, transglutaminases, cystatins, and filaggrin ^[7][35][57,80]. Furthermore, DPE impaired mitochondrial oxidative phosphorylation and cell migration in these cells. These effects could be partially avoided or restored by the treatment of the cells with the antioxidant vitamin E ^[35][57].

PM causes inflammation in the skin through increased IL-8, MMP-1, ROS production, and neutrophil infiltration in the deep dermis ^[36][104]. Fibroblasts cultivated with conditioned medium obtained from immortalized human keratinocytes (HaCaT) treated with PM displayed increased nuclear translocation of p65 and p50 as well as increased ROS production, morphological changes, and secretion of SASP components including prostaglandin E2, COX-2, TNF-α, IL-1β, and IL-6 ^[23][93]. It is well established that the expression and release of TNF-α is increased upon UV exposure ^[37][105] as well in some skin diseases such as vitiligo ^[38][106].

Other studies have shown that the exposition of HaCaT cells or reconstructed human epidermis to PM induced upregulation of NF-κB, COX-1 as well as IL-1α leading to skin barrier dysfunction ^[8][81]. In addition, an increased autophagic activity shown by the turnover of the light chain 3 Ι (LC3) to LC3 II, expression of p62, and PM internalization in the autolysosomes was observed after exposure of fibroblasts to air pollutants such as PM ^[39][40][107,108].

The PM particles can transport organic chemicals and metals into cells which when localizing in the mitochondria can directly generate ROS ^[15][2]. Mostly, PM particles contain PAH which can penetrate the skin. PAH is an activator of AhR in melanocytes and keratinocytes and exposition of the skin to this chemical can influence epidermal turnover, melanogenesis, and differentiation ^[3][14][9,86]. PAH have synergistic effect with UVA and both contribute to skin carcinogenesis and to the appearance of skin pigmentation disorders such as senile lentigines ^{[4][21][22][41][42][43]}[5,53,70,92,109,110]. Interestingly, exposure of melanocytes to PM induces apoptosis through cytochrome C release and activation of caspase-3 ^[44][111]. These events are linked to the disappearance of melanocytes which is considered one of the main pathogenic mechanisms of vitiligo.

The effects of PM 2.5 and 10 are linked to different skin diseases such as AD and allergies ^[29][45][45,112]. Several studies have demonstrated that AD skin, as well as healthy skin exposed to PM, display skin barrier disruption due to decreased expression of epidermal structural proteins such as filaggrin, E-cadherin, and cytokeratins ^[46][47][48][43,44,113]. Additionally, it is suggested that AD can be influenced by the exposure to air pollution resulting in imbalance of immune cell response and IgE production, activation of AhR/NF-κB, and the generation of ROS, and these effects can be prevented by improved air quality ^[4][13][47][5,44,85].

Cigarette smoke is composed of different chemical substances including reactive oxygen species, carbon monoxide, and reactive nitrogen species. Smoking is associated with lung cancer as well as with cutaneous squamous cell carcinoma. PAH, one important component of cigarette smoke, is a major contributor to cancer. PAH induces AhR and subsequently CYP1A1 which leads to the formation of DNA adducts and can result in cancer development ^[49][50][114,115].

The effects of cigarette smoke are cumulative and associated with the appearance of signs of premature aging, especially in the facial skin. Among them the most common are deep wrinkles, dryness, leathery texture, sagging, premature graying, and orange to purple discoloration of the skin ^[2][17][22][8,53,88]. Exposition of the skin to cigarette smoke induces oxidative stress and the impairment of the antioxidant system. The consequences are transepidermal water loss, lipid peroxidation, cell death, and degeneration of connective tissue by MMP-1 and -3 ^[7][49][51][80,114,116]. In keratinocytes, cellular redox homeostasis and colony-forming potential was affected in response to exposure to tobacco smoke components such as PAH and PM ^[21][92]. In humans, a study comparing smokers and nonsmokers revealed the occurrence of shorter telomeres, a sign of cellular senescence, in peripheral white blood cells of smokers ^[28][98]. Synergistic effects may occur upon the combined exposure to UV and cigarette smoke leading to epidermal barrier disruption, increased erythema, and decreased elasticity ^[2][17][22][8,53,88]. Furthermore, a three months’ whole body exposure of mice to tobacco smoke caused premature aging evidenced by the loss of collagen as well as hair loss and premature graying due to increased apoptosis and decreased melanogenesis, respectively ^[52][117]. Additionally, the combined exposure of tobacco smoke with ultraviolet light, exacerbated the effects of aging by the upregulation of p16 expression. These effects could be prevented by N-acetylcysteine (NAC) suggesting that premature aging triggered by cigarette smoke exposition is driven by ROS ^[4][5]. Other studies showed that exposure of skin cells, ex vivo skin biopsies, or reconstructed skin to cigarette smoke leads to production of pro-inflammatory cytokines and MMPs, lipid peroxidation, and downregulation of differentiation proteins such as loricrin and this, in turn, resulting in the impairment of skin barrier structure and function ^[49][50][53][114,115,118].

Besides the consequences of topical exposition of the skin to pollution, the inhalation of pollution has systemically effects to the skin. In a recent in vivo study, it was demonstrated that chronic inhalation of tobacco smoke leads to changes in the composition and deposition of elastin and fibrillin-rich microfibrils in the dermis which is accompanied by a higher stiffness of the skin ^[54][119].

In a study using a model of skin aging induced by tert-butyl hydroperoxide (tBHP), Wedel and colleagues showed that skin exposed to this chemical displayed downregulation of collagen synthesis and the increased secretion of MMPs. tBHP is categorized as an oxidative stress inducer which leads to the accumulation of intracellular ROS and deplete the antioxidant mechanisms and can be used as a proxy to study mechanisms that recapitulate the exposition of the skin to environmental stressors such as cigarette smoke ^[55][61].

Stratospheric ozone has a protective role for earth-living organisms by filtering UV radiation. Ozone (O₃) in the troposphere reaches the skin surface and reacts with molecules such as lipids and proteins in the stratum corneum ^[3][56][9,120]. In general, ozone causes oxidative stress, increased lipid peroxidation, AhR induction, and depletion of Vitamins C and E in human skin ^[57][58][121,122]. A report has shown that in human keratinocytes, exposure to ozone leads to lactate dehydrogenase release, reduced cell proliferation, lipid peroxidation, and NF-κB activation and these effects can be prevented by pretreatment with antioxidant mixtures ^[59][123]. Another study has shown that the combination of UVA and ozone has a synergistic effect and causes increased oxidative stress of the skin and Nrf2 expression in keratinocytes leading to skin inflammation, formation of wrinkles, and pigment spots ^[2][3][36][8,9,104]. In human skin O₃ leads to activation of NF-κB, MMP-9, COX-2, and lipid peroxidation in the epidermis, whereas in the dermis expression of collagen-1 and -3 are downregulated. These consequences are accelerating the appearance of skin aging signs including the formation of wrinkles and senile lentigines as well as affecting wound healing ^[60][61][124,125].

The earth crest is formed by different components, among them heavy metals such as chromium, lead, cadmium, silver, nickel, mercury, manganese, and vanadium ^[2][8]. These metals can contaminate the water and food supply and cannot be degraded or destroyed. These substances are important trace elements for the maintenance of metabolic reactions but in higher concentrations they become toxic to the human body [10]. Heavy metals from industrial fumes reach plants through acidic rain. For instance, tobacco leaves are rich in cadmium which, when inhaled, cannot be excreted from the human body and leads to long term effects and damage to the lungs, kidneys, and bones ^[1][78]. A study showed that keratinocytes and skin explants exposed to dust particles containing heavy metals or heavy metals alone displayed increased expression of the pro-inflammatory cytokines IL-6, IL-8, caspase-14, and granulocyte macrophage colony-stimulating factor which are known to alter epidermal differentiation, ECM, apoptosis, DNA damage, lipid peroxidation, and skin immunity resulting in cutaneous inflammation and inflammation skin disorders ^[14][62][86,126].