
P. Schroeder, PhD and J. Krutmann, MD
 Institut für Umweltmedizinische Forschung (IUF) at the Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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 aging4,5 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
- Krutmann J, Gilchrest BA. Photoaging of skin. In: Gilchrest BA, Krutmann J (eds). Skin aging. New York: Springer, p33-44 (2006).
 - 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).
 - 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).
 - 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).
 - 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).
 - 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).
 - 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).
 - 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).
 - Allemann IB, Baumann L. Botanicals in skin care products. Int J Dermatol 48(9):923-34 (2009 Sep).
 - Krutmann J, Yarosh D. Modern photoprotection of human skin. In: Gilchrest BA, Krutmann J (eds). Skin aging. New York: Springer, p103-12 (2006).
 - 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).
 - 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).
 - 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).
 - 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).
 
 
 





