P. Schroeder, PhD and J. Krutmann, MD
Institut für Umweltmedizinische Forschung (IUF) at the Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
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.
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 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
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 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.
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
- 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).