ABSTRACT
Human skin is increasingly exposed to sunlight. In order to achieve complete protection against the cumulative detrimental effects from sun exposure, topical strategies must shield against the range of solar wavelengths that can damage the skin. Importantly, the harm sustained by the skin is not limited to that caused by the ultraviolet (UV) portion of the light spectrum, but also includes the adverse effects inflicted by near infrared energy. Consequently, in an attempt to provide the necessary broad spectrum coverage, innovative research continues through the exploration of new compounds and novel combinations of chemical and physical UV filters with molecules that are capable of interfering with and/or preventing the deleterious effects of infrared A (IRA) radiation. Existing examples of infrared-protective active agents include mitochondrially targeted antioxidants of synthetic or natural origin.

Key Words:
infrared, IRA, photoaging, sunscreens, skin protection, UVA, UVB, ultraviolet

Adverse Skin Effects from Solar Radiation

Despite some positive and health promoting effects from
sunlight, it is apparent that high acute, chronic low dose,
and/or unprotected exposure have several detrimental
effects, including premature skin aging and the development
and progression of cancer.¹ For many years the focus of
research, and therefore for protective strategies, has been
centered on the ultraviolet (UV) part of sunlight, i.e.,
ultraviolet B (UVB) (290-320 nm) and ultraviolet A (UVA)
(320-400 nm), because their relatively high photon energy
causes macroscopic skin changes that are visible even after
a short duration of exposure. However, UV radiation only
accounts for approximately 7% of the sun’s energy,² which
underlines the necessity to consider the detrimental effects
from other parts of the sunlight spectrum. Accordingly, we
and others identified infrared A (IRA) (760-1440 nm) as a
damaging environmental factor to skin through its ability
to engender alterations in gene expression of skin cells at
multiple points,³ resulting in accelerated skin aging^4,5 and
contributing to the development of cancer.⁶

It is well known that the most effective protection against
UV radiation is sun avoidance, e.g., by limiting exposure, or
at least direct exposure during peak times, and by wearing
appropriate clothing. However, in Western civilizations the
level of sun exposure continues to rise, e.g., for recreational
reasons and due to increased life expectancy.

Complete Photoprotection Considers All Relevant Parts of the Solar Spectrum

Taking into account recent findings, it is evident that effective
photoprotection must provide more than UV coverage, but
rather it should protect against IRA as well. It is estimated
that about one-third of solar energy is comprised of IRA,
which is capable of deep skin penetration.²

Multipronged Approach to Complete Photoprotection

Modern topical photoprotection integrates both primary
protective factors (e.g., organic or inorganic light filtering
agents) that absorb or reflect UV radiation and secondary
factors (e.g., antioxidants, osmolytes, and DNA repair
enzymes) that can disrupt the photochemical cascade
triggered by UV-penetration, thereby limiting skin damage.

Primary Photoprotection

Primary photoprotection is achieved by using physical and/
or chemical UV filtering agents, which have been key active
components in commercially available sunscreens for more
than 60 years. The most frequently used physical UV filters
are the inorganic micropigments, zinc oxide and titanium
dioxide.

Most chemical filters absorb UV energy across a relatively
narrow or specific wavelength range, converting UV
radiation to longer wavelength photons. Due to the limited
absorption spectrum of any single ingredient, a combination
of sunscreen actives is required to yield both UVA and UVB
protection, but the degradation of some UVA filters by
sunlight presents formulary challenges. However, in recent
years, tremendous progress has been made in developing
more photostable UV filters, such as ecamsule (Mexoryl™
SX) and drometrizole trisiloxane (Mexoryl™ XL) and by
formulating efficient combinations, such as avobenzone
combined with diethylhexyl 2,6-naphthalate and oxybenzone
(Helioplex™). Concerning UV filters used in commercially
available products, it should be noted that there are
differences between approved agents in the European Union
when compared with the US, as the US FDA has been more
conservative in sanctioning new chemical sunscreens. As for
protection against other parts of the light spectrum (other
than UV), these chemical compounds do not provide any
benefit beyond their UV specificity.

Secondary Photoprotection

Secondary photoprotection involves the use of active agents
to interfere with or counteract the inherent photochemical
processes that can induce DNA damage in skin cells.
Secondary photoprotection may be achieved by an extremely
heterogeneous and constantly growing group of molecules
that are termed “actives”. Examples of such actives include
antioxidants, osmolytes, and DNA repair enzymes7,8 (e.g.,
photolyase and T4 endonuclease V).

Antioxidants that are typically used in sunscreens and
other cosmetic products are comprised of vitamins and
polyphenols. Prime examples of vitamins formulated in
sunscreens are water soluble vitamin C and lipophilic
vitamin E. The term “polyphenols” refers to compounds that
possess at least 2 adjacent hydroxyl groups on a benzene ring.
Natural polyphenols (e.g., flavonoids and procyanidins) are
present in numerous foods and have been demonstrated to
provide protective properties through topical application.9,10
In addition, antioxidants have also been shown to protect
against IRA. Accordingly, significant importance resides with
molecules that are targeted toward mitochondria, because
of their central role in IRA-induced adverse effects.3,5,11,12
However, it should be noted that the precise mechanism of
action of topically applied actives remain to be elucidated;
there is a need to fully understand their effects at both cellular
and molecular levels prior to supporting their therapeutic
benefits as photoprotective agents.

Osmolytes are small molecules that control and stabilize the
cellular environment by regulating hydration and responses
to stress conditions. Osmolytes (compatible organic solutes)
are not only utilized by cells to control cell volumes, but they
have been identified as integral parts of the cellular defence
against environmental noxae. The osmolytes taurine13
and ectoine14 have been demonstrated to protect against
detrimental UV effects and are amalgamated into several
commercially available sunscreens.

Conclusion

Complete topical photoprotection can only be obtained if a
sunscreen formula defends against UVB, UVA, and IRA.
Whether additional wavelengths contribute to skin damage
is currently not known. In order to achieve as near complete
broad spectrum protection as is possible, a sunscreen must
combine multiple therapeutic approaches that incorporate
both essential elements of primary and secondary
photoprotection.

References

1. Krutmann J, Gilchrest BA. Photoaging of skin. In: Gilchrest BA, Krutmann J (eds). Skin aging. New York: Springer, p33-44 (2006).
2. Kochevar IE, Taylor CR, Krutmann J. Fundamentals of cutaneous photobiology and photoimmunology. In: Wolff K, Goldsmith LA, Katz S, et al. (eds). Fitzpatrick’s dermatology in general medicine, 7th ed. New York: McGraw-Hill, p797-808 (2008).
3. Calles C, Schneider M, Macaluso F, et al. Infrared A radiation influences the skin fibroblast transcriptome: mechanisms and consequences. J Invest Dermatol (In press 2010).
4. Schroeder P, Pohl C, Calles C, et al. Cellular response to infrared radiation involves retrograde mitochondrial signaling. Free Radic Biol Med 43(1):128-35 (2007 Jul 1).
5. Schroeder P, Lademann J, Darvin ME, et al. Infrared radiationinduced matrix metalloproteinase in human skin: implications for protection. J Invest Dermatol 128(10):2491-7 (2008 Oct).
6. Jantschitsch C, Majewski S, Maeda A, et al. Infrared radiation confers resistance to UV-induced apoptosis via reduction of DNA damage and upregulation of antiapoptotic proteins. J Invest Dermatol 129(5):1271-9 (2009 May).
7. Dong KK, Damaghi N, Picart SD, et al. UV-induced DNA damage initiates release of MMP-1 in human skin. Exp Dermatol 17(12):1037-44 (2008 Dec).
8. Yarosh DB, O’Connor A, Alas L, et al. Photoprotection by topical DNA repair enzymes: molecular correlates of clinical studies. Photochem Photobiol 69(2):136-40 (1999 Feb).
9. Allemann IB, Baumann L. Botanicals in skin care products. Int J Dermatol 48(9):923-34 (2009 Sep).
10. Krutmann J, Yarosh D. Modern photoprotection of human skin. In: Gilchrest BA, Krutmann J (eds). Skin aging. New York: Springer, p103-12 (2006).
11. Krutmann J, Schroeder P. Role of mitochondria in photoaging of human skin: the defective powerhouse model. J Investig Dermatol Symp Proc 14(1):44-9 (2009 Aug).
12. Schroeder EK, Kelsey NA, Doyle J, et al. Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal 11(3):469-80 (2009 Mar).
13. Rockel N, Esser C, Grether-Beck S, et al. The osmolyte taurine protects against ultraviolet B radiation-induced immunosuppression. J Immunol 15;179(6):3604-12 (2007 Sep).
14. Buenger J, Driller H. Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Physiol 17(5):232-7 (2004 Sep-Oct).

ABSTRACT

Photoaging and skin damage that is caused by solar radiation is well known. We have recently learned that within the solar spectrum this damage not only results from ultraviolet (UV) radiation, but also from longer wavelengths, in particular near infrared radiation. Accordingly, infrared radiation (IR) has been shown to alter the collagen equilibrium of the dermal extracellular matrix in at least 2 ways: (1) by leading to an increased expression of the collagen degrading enzyme matrixmetalloproteinase-1 while (2) decreasing the de novo synthesis of the collagen itself. Infrared-A (IRA) radiation exposure, therefore, induces similar biological effects to UV, but the underlying mechanisms are substantially different. IRA acts via the mitochondria and therefore protection from IR requires alternative strategies.

Key Words:
infrared, photoaging, skin aging, solar radiation

Physics of Infrared (IR) Radiation

Solar radiation in wavelengths of 290nm to 4000nm reaches the earth’s surface after atmospheric filtering. This part of the electromagnetic spectrum is divided into 3 major bands:

ultraviolet (UV) radiation (290-400nm)
visible light (400-760nm)
IR radiation (760-4000nm)

IR is further divided into IRA (760-1440nm), IRB (1440-3000nm), and IRC (3000nm-1mm). Of the total amount of solar energy reaching the human skin, 54% is IR, while only 7% is UV.¹ Roughly 30% of the total solar energy is IRA, which penetrates deeply into the human skin.¹ Most of the IRA radiation load on human skin is of solar origin, but in recent years artificial IRA sources are used increasingly. In addition to therapeutic approaches, the use of IRA for wellness and lifestyle purposes is steadily rising.

Detrimental Effects of IRA and Underlying Molecular Mechanisms

More than 20 years ago, Kligman reported that IR in guinea pigs causes actinic skin damage that resembled skin damage caused by UV.² This observation has since been confirmed in another animal model.³ Moreover, IRA was reported to interfere with apoptotic pathways, thus preventing UV-damaged cells from executing programmed cell death, which indicates a co-carcinogenic potential for IRA.^4,5 Until now in vivo carcinogenesis studies for IRA alone and in combination with other noxae like UV have not been published. For IRC, the occurrence of a skin lesion described as erythema ab igne, which may progress to squamous cell carcinoma, has been reported.⁶ However, interference with apoptotic pathways,⁴ involvement in the repair of damaged DNA,⁵ stimulation of proliferation and accelerated woundhealing⁷ underline the necessity to further investigate the role of IRA in photocarcinogenesis.

The molecular basis of IRA induced photoaging of the skin was assessed by Schieke et al,⁸ who were the first to show that physiological doses of IRA lead to a disturbance of the dermal extracellular matrix by upregulation of the expression of the collagen degrading enzyme matrixmetalloproteinase-1 (MMP1). This finding was confirmed in independent in vivo and in vitro studies by different laboratories.^9,10 In addition, IRA exposure was recently shown to lead to a downregulation of collagen de novo synthesis.¹¹ The IRA-induced upregulation of MMP1 was found to be different from that induced by UV at the mechanistic level, since it involves the formation of mitochondrial reactive oxygen species (ROS) and the subsequent initiation of a retrograde signaling response (i.e., from the mitochondria to the nucleus) in human skin.^12,13 The omnipresence of IRA, its biophysical properties, and the fact that it acts differently from UV points to the necessity of including specific IRA-directed strategies in modern sunscreens.

Protection Strategies Against IRA

Complete photoprotection of human skin must include protection against IRA. Currently there are no specific chemical or physical filters directed against IRA that are available, or at least the available compounds need to be tested for their IRA-filtering capacity. While it is unlikely, that UV-specific filters work against IRA, physical filters might provide protection in addition to their potential against UV. Controlled studies determining the effectiveness of UV filters in IRA protection are currently not available.

An alternative approach for photoprotection against IRA is the use of antioxidants, especially mitochondrially-targeted antioxidants, e.g., epigallocatechin gallate (found in grape seed extracts and tea extracts), and mitoquinone (MitoQ™, Antipodean Pharmaceuticals), which is a coenzyme Q derivative. Accordingly, topically applying such antioxidants on human skin in vivo prior to IRA treatment has shown that it significantly abrogates the IRA-induced detrimental shift in dermal gene expression.¹⁰

Conclusion

Recent data clearly indicate that in addition to UV, protection against IRA must be taken into account when it comes to modern sun protection. IRA photoprotection requires specific strategies because existing UV protective measures miss the problem. A feasible and effective approach is the topical application of mitochondrially-targeted antioxidants. In addition, unnecessary exposure to IRA radiation from artificial irradiation devices should be avoided.

References

1. Kochevar IE, Taylor CR, Krutmann J. Fundamentals of cutaneous photobiology and photoimmunology. In: Wolff K, Goldsmith LA, Katz S, et al. (Eds.). Fitzpatrick’s Dermatology in General Medicine, 7th ed. McGraw-Hill:New York (2008).
2. Kligman LH. Intensification of ultraviolet-induced dermal damage by infrared radiation. Arch Dermatol Res 272(3-4):229-38 (1982).
3. Kim HH, Lee MJ, Lee SR, et al. Augmentation of UV-induced skin wrinkling by infrared irradiation in hairless mice. Mech Ageing Dev 126(11):1170-7 (2005 Nov).
4. Frank S, Oliver L, Lebreton-De Coster C, et al. Infrared radiation affects the mitochondrial pathway of apoptosis in human fibroblasts. J Invest Dermatol 123(5):823-31 (2004 Nov).
5. Jantschitsch C, Majewski S, Maeda A, et al. Infrared radiation confers resistance to UV-induced apoptosis via reduction of DNA damage and upregulation of antiapoptotic proteins. J Invest Dermatol 129(5):1271-9 (2009 May).
6. Dover JS, Phillips TJ, Arndt KA. Cutaneous effects and therapeutic uses of heat with emphasis on infrared radiation. J Am Acad Dermatol 20(2 Pt 1):278-86 (1989 Feb).
7. Danno K, Mori N, Toda K, et al. Near infrared irradiation stimulates cutaneous wound repair: laboratory experiments on possible mechanisms. Photodermatol Photoimmunol Photomed 17(6):261-5 (2001 Dec).
8. Schieke S, Stege H, Kürten V, et al. Infrared-A radiation-induced matrix metalloproteinase 1 expression is mediated through extracellular signal-regulated kinase 1/2 activation in human dermal fibroblasts. J Invest Dermatol 119(6):1323-9 (2002 Dec).
9. Kim MS, Kim YK, Cho KH, et al. Regulation of type I procollagen and MMP-1 expression after single or repeated exposure to infrared radiation in human skin. Mech Ageing Dev 127(12):875-82 (2006 Dec).
10. Schroeder P, Lademann J, Darvin ME, et al.. Infrared radiation-induced matrix metalloproteinase in human skin: implications for protection. J Invest Dermatol 128(10):2491-7 (2008 Oct).
11. Buechner N, Schroeder P, Jakob S, et al. Changes of MMP-1 and collagen type Ialpha1 by UVA, UVB and IRA are differentially regulated by Trx-1. Exp Gerontol 43(7):633-7 (2008 Jul).
12. Schroeder P, Pohl C, Calles C, et al. Cellular response to infrared radiation involves retrograde mitochondrial signaling. Free Radic Biol Med 43(1):128-35 (2007 Jul 1).
13. Krutmann J, Schroeder P. Role of mitochondria in photoageing of human skin: the defective powerhouse model. J Invest Dermatol Symp. Proceed. [in press].