Reference Work Entry

Textbook of Aging Skin

pp 421-425

Infrared A-induced Skin Aging

  • Peter SchroederAffiliated withEnvironmental Health Research Institute (IUF) at the Heinrich-Heine-University
  • , Jean KrutmannAffiliated withEnvironmental Health Research Institute (IUF) at the Heinrich-Heine-University

Abstract

Extrinsic skin aging has, for many years, been mainly attributed to ultraviolet (UV) radiation. Recently, it has become evident that other parts of the solar electromagnetic spectrum contribute as well. Among these, infrared radiation, especially Infrared A, has received increasing attention. This chapter will summarize the current knowledge about the epidemiological evidence, molecular principles, and prevention/protection, as it concerns skin aging induced by Infrared A.

Abstract

Extrinsic skin aging has, for many years, been mainly attributed to ultraviolet (UV) radiation. Recently, it has become evident that other parts of the solar electromagnetic spectrum contribute as well. Among these, infrared radiation, especially Infrared A, has received increasing attention. This chapter will summarize the current knowledge about the epidemiological evidence, molecular principles, and prevention/protection, as it concerns skin aging induced by Infrared A.

42.1 Introduction

Extrinsic skin aging has, for many years, been mainly attributed to ultraviolet (UV) radiation. Recently, it has become evident that other parts of the solar electromagnetic spectrum contribute as well. Among these, infrared radiation, especially Infrared A, has received increasing attention. This chapter will summarize the current knowledge about the epidemiological evidence, molecular principles, and prevention/protection, as it concerns skin aging induced by Infrared A.

42.2 Infrared Radiation

42.2.1 Physical Basics and Natural and Artificial Sources

Solar radiation is filtered by the earth’s atmosphere; the part reaching the earth surface includes the wavelengths from 290 to 4,000 nm and is divided into three bands: ultraviolet radiation (UV, 290–400 nm), visible light (400–760 nm), and infrared radiation (IR, 760–4,000 nm). Infrared radiation is further subdivided into IRA (λ = 760–1,440 nm), IRB (λ = 1,440–3,000 nm), and IRC (λ = 3,000 nm–1 mm).

While the photon energy of IR is lower than that of UV, the total amount of solar energy reaching human skin contains approximately 54% IR, while UV only accounts for 7% [1]. Most of the IR radiation lies within the IRA band (∼30% of total solar energy), which deeply penetrates the human skin, while IRB and IRC only affect the upper skin layers (Fig. 42.1 ). In comparison, IRA penetrates better than UV into the skin, with approximately 50% reaching the dermis [13].
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Figure 42.1

Skin penetration of infrared radiation. Different wavelengths of natural and artificial radiations have different penetration capabilities. IRA penetrates well into the skin, approximately 50% of IRA is absorbed in the dermis. IRB reaches the dermis as well, while IRC is nearly completely absorbed in the epidermis

The main source of IR radiation is the sun; the actual solar dose reaching the skin is influenced by several factors: ozone layer, position of the sun, latitude, altitude, cloud cover, and ground reflections. Based on these parameters, it should be noted that the overall composition of sunlight, e.g., in terms of the UV/IRA ratio is changing throughout the day. In addition to natural sunlight, artificial IR sources are constantly gaining importance; they are used for therapeutic as well as for lifestyle purposes. While therapeutic use of IRA provides beneficial effects, for example, in wound healing, lifestyle-motivated applications of IRA, e.g., for “wellness” irradiations or for means of skin rejuvenation appear to be quite paradoxical [4].

42.2.2 Infrared Radiation and Skin Aging

The role of IR radiation in premature skin aging was described over 20 years ago by L. Kligman [5]. She was the first to report that infrared radiation enhances UV-induced skin damage in guinea pigs. This prompted her to investigate the effect of IR alone; as a consequence, she could demonstrate that IR leads to elastosis, with “IR inducing the production of many fine, feathery fibers” and “a large increase in ground substance, a finding also seen in actinically damaged human skin.” From these observations, she has concluded that IR radiation contributes to skin aging. It took, however, almost 20 years until the underlying molecular mechanisms could be identified.

42.2.3 Molecular Mechanisms

Schieke et al. reported in 2002 that low, physiologically relevant doses of IRA lead to a disturbance of the dermal extracellular matrix. IRA irradiation results in an induction of Matrixmetalloproteinase-1 (MMP-1) in vitro in human dermal fibroblasts, while expression of the respective tissue inhibitor TIMP-1 was not increased. This finding has, since then, been confirmed in independent studies by different workgroups in vitro and in vivo [6, 7].

Matrixmetalloproteinases (MMPs) are zinc-dependent endopeptidases responsible for the degradation of extracellular matrix components such as collagen and elastin. Under physiological conditions, MMPs are part of a coordinate network and are precisely regulated by their endogenous inhibitors, tissue inhibitors of MMPs (TIMPs). The unbalanced activity of MMPs with excessive proteolysis is thought to be a major pathophysiological factor in extrinsic skin aging. The increased expression of MMPs without a respective increase in TIMP expression results in the cleavage of fibrillar collagen, and thus impairs the structural integrity of the dermis [810].

This impairment can be partially countered by an increased expression of collagen itself. It is therefore important to note that IRA has recently been found to decrease the expression of the dominant human collagen gene Col1a1 in vitro and in vivo [11, 6].

Taken together, IRA disturbs the collagen equilibrium of the skin in two ways: (1) by increasing the amount/activity of MMP-1, which results in an increased collagen degradation and (2) by decreasing de novo synthesis of collagen.

While the biological endpoints of IRA irradiation resemble those found after UV irradiation, the underlying cellular molecular processes are completely different. This is particularly evident if UVA and IRA are being compared: the primal event in both cases is an increased amount of reactive oxygen species (ROS), which on a first glare seems to indicate a similarity rather than a difference. More detailed analysis – however – revealed huge differences between UVA and IRA. UVA induces an increased production of ROS by NADPH-oxidases, which are located in the cytoplasma membrane [12] and in addition repetitive UVA irradiation results in damage to the mitochondrial DNA (mtDNA) [13]. IRA, on the other hand acts via a disturbance of the mitochondrial electron transport chain (mtETC). This multiprotein facility, driven by reduction equivalents (NADH/H + and FADH2), is responsible for energy conservation by transferring electrons to oxygen, while building up an electrochemical proton gradient across the inner mitochondrial membrane, which in turn fuels the production of ATP from ADP and Pi. As this process is not error free, relatively small amounts of ROS are always generated. Upon IRA irradiation this amount is significantly increased [4].

ROS are often recognized only as damaging agent, but they are well known to function in terms of cellular signaling. Reactive oxygen species (ROS) can serve to trigger molecular signaling responses and several studies indicate that ROS cause an inactivation of protein-tyrosine phosphatases (PTPs) by oxidizing conserved cysteine residues in the active sites of PTPs and thereby lead to a net increase in kinase phosphorylation/activation [14].

After IRA irradiation, not only the mitochondrial levels, but also the cellular ROS levels are increased and a disturbance of the cellular glutathione (GSH) equilibrium is observed [15]. GSH is one of the most important endogenous antioxidants; it can prevent or repair oxidative damage, and as a consequence it is oxidized itself, forming the glutathione dimer (GSSG). In this regard, IRA irradiation leads to a significant shift of the GSH/GSSG equilibrium towards the oxidized form [15].

IRA-induced ROS production is not just a by-product of the irradiation, but of functional relevance because boosting the cellular antioxidative defense by increasing the cellular GSH content abrogated the IRA-induced upregulation of MMP-1 [15]. In addition, use of specific antioxidants in cell culture has also been shown to decrease the IRA-induced effects [7].

Mitochondria are known to act as a hub for cellular signaling with disruption of the mtETC being a prominent inducer of such retrograde (i.e., from mitochondria to nucleus) signaling [16]. In contrast to anterograde signaling processes here the nuclear gene expression is regulated by events originating in the mitochondria. The IRA-induced increase in mitochondrial ROS was recently found to initiate such a retrograde signaling cascade (Fig. 42.2 ).
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Figure 42.2

Infrared A-induced signal transduction. IRA radiation leads to an increased amount of mitochondrial ROS, which in turn leads to initiation of retrograde signaling, finally resulting in an increased expression of MMP-1 mRNA and protein and a decreased expression of Col1α1

Downstream of mitochondrial ROS, the IRA radiation-induced signaling pathway relevant for MMP-1 induction has been found to involve the activation of MAPKinases. Three distinct MAPK pathways have been characterized: the extracellular signalregulated kinase 1/2 (ERK1/2) pathway (Raf-MEK1/2-ERK1/2), the c-Jun N-terminal kinase pathway (MEKK1/3-MKK4/7-JNK1/2/3), and p38 (MEKK-MKK3/6-p38 a–d) pathway also termed stress-activated protein kinases (SAPKs). The ERK1/2 pathway is primarily induced by mitogens such as growth factors, whereas the SAPK pathways are predominantly induced by inflammatory cytokines as well as environmental stress such as UV, heat, and osmotic shock. Activated MAPKs translocate to the nucleus, where they phosphorylate and activate transcription factors such as c-Jun, c-Fos, ATF-2, and ternary complex factors (TCF) leading to the formation and activation of homo- or heterodimeric forms of the transcription factor AP-1. The promoter region of MMP-1 carries multiple AP-1-binding sites. For IRA, it has been demonstrated that ERK1/2 and p38 are activated in dermal fibroblasts, but that only inhibition of ERK1/2 activation subdues the IRA-induced increase of MMP-1 (reviewed in [17]).

Although up to now the main research focus has been on MMP-1 and Col1a1 it is very likely that the IRA-induced activation of MAPKinases affects the regulation of other genes as well. Indeed, several additional effects of IRA are known: Kim et al. reported that infrared exposure is involved in neoangiogenesis in human skin, because IRA induces an angiogenic switch by altering the balance between the angiogenic inducer VEGF and the angiogenic inhibitor TSP-2 [18]. Interestingly, increased neoangiogenesis is a prominent feature of photoaged human skin [19]. Others found that IRA irradiation led to a decrease in epidermal proliferation, Langerhans cell density, and contact hypersensitivity reaction in mice [20], and a subsequent study by the same group indicates that IRA influences cutaneous wound repair by altering the levels of transforming growth factor (TGF)-b1 and MMP-2 [21]. Yet another study showed an influence of IRA on protein expression of ferritin: an increased ferritin expression was detected after IRA irradiation of keratinocytes and fibroblasts [22]. Ferritin is involved in the cellular antioxidative defense and the induction of this putative defense system in human skin most likely reflects a cellular response to oxidative processes triggered by IRA. Frank et al. showed that IRA interferes with apoptotic pathways, namely the mitochondrial apoptosis pathway [23] and reported that IRA signals via p53 [24]. The abrogating effect of IRA on apoptosis induced by lethal doses of extrinsic factor has recently been confirmed by another study [25].

42.2.4 Dosimetry of IRA

Human dermal fibroblasts withstand IRA doses up to at least 1,200 J/cm2 [26], but the gene regulatory effects can already be observed at much lower, physiologically relevant dosage, i.e., 54 [8], 240 [4], or 360 J/cm2 [15]. Increased levels of cytosolic and mitochondrial ROS were detected even after a treatment with 30 J/cm2 [15].

42.2.4.1 IRA Chromophores

While the endogenous chromophores for IR are very likely to be part of the mtETC [27] and remain to be identified, several exogenous chromophores for IR are known. They are used for therapeutic purposes, e.g., in photodynamic therapy, and include palladium-bacteriopheophorbide and indocyanine green [28, 29].

42.2.4.2 Protection Against IRA

Up to now, photoprotection of human skin has focused against UVB and/or UVA radiation. The studies discussed above indicate, however, that protection against IRA radiation has to be included in order to achieve complete protection.

In this regard antioxidants appear to be promising. Based on the fact that mtROS are functionally relevant in the IRA-induced effects, antioxidants that target the mitochondria theoretically represent potential IRA protective substances. Indeed, it has been demonstrated in vitro and in vivo that such specific antioxidants protect against detrimental IRA effects, e.g., IRA-induced MMP-1 expression [7].

In contrast, there are currently no chemical or physical UV filters available, which are suited for commercial suncare products, and which have been shown to provide IRA protection.

The protective effect of textiles remains to be evaluated in terms of IRA protection. There is, however, data available showing that use of a black cloth at least partially provides IRA protection [18].

Finally, the topic of avoidance has to be discussed. Until now, there is no information source available that would provide a measure on the actual IRA load that would be comparable to the well-established UV index. Establishing a respective IRA index might be a considerable contribution.

42.3 Conclusion

As skin aging is a complex process, it is not surprising that ongoing research efforts uncover more and more environmental factors enfolding detrimental effects on the skin. Regarding natural sunlight or artificial sources of its components there is a major doubt that whether in addition to UV, IRA protection also has to be taken into account.

IRA photoprotection requires specialized strategies with topical application of mitochondrially targeted antioxidants being a promising option.

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© Springer-Verlag Berlin Heidelberg 2010
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