UV Light and Skin Aging

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UV light and skin aging

Article · September 2014 DOI: 10.1515/reveh-2014-0058 · Source: PubMed

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J é ssica Eleonora Pedroso Sanches Silveira* and D é bora Midori Myaki Pedroso UV light and skin aging

Abstract: This article reviews current data about the rela- signs of aging. Physiological changes in aged skin include tionship between sun radiation and skin, especially with structural and biochemical changes as well as changes regards ultraviolet light and the skin aging process. The in neurosensory perception, permeability, response to benefits of sun exposition and the photoaging process are injury, repair capacity, and increased incidence of some discussed. Finally, the authors present a review of photopro- skin diseases (5) . tection agents that are commercially available nowadays. The skin aging process occurs in the epidermis and dermis. Although the number of cell layers remains stable, Keywords: photoaging; sun protection; ultraviolet (UV) the skin thins progressively over adult life at an accelerat- exposure. ing rate. The epidermis decreases in thickness by about 6.4% per decade on average, with an associated reduction in epidermal cell numbers (6) , particularly in women. DOI 10.1515/reveh-2014-0058 Received August 4 , 2014 ; accepted August 15 , 2014 Further, dermis thickness decreases with age, and thinning is accompanied by a decrease in both vascularity and cellularity (5) . Aged skin turns dryer (7) , and this can be proven by Aging transepidermal water loss (TEWL) measurements. Base- line TEWL decreases with age, an observation believed to The process of aging begins at the moment of birth, but be due to the reduction of the water content of aged skin, people now live longer than ever before. This is due to which can be associated with a profound change in barrier the continued advancements in medicine involving new integrity. Although the number of sweat glands does not technologies for immunization, organ transplant, reduced change, sebum production decreases by as much as 60%. infection (1) and equipment to support life, which have all A reduction of the natural water and fat emulsion on the become more available. skin is also observed, as is water content in the stratum In many countries a demographic transition is occur- corneum. Global lipid content of the aged skin is reduced ring, involving aging of the population and reduced by as much as 65%. Changes in the amino acid compo- birthrates, as well as large-scale migrations. In the next sition in aged skin may reduce the amount of cutaneous 50 years, about one-third of women will be menopausal, natural moisturizing factor, thereby decreasing its capac- and anti-aging medicine will gain importance (2) because ity for water binding (5) . no one especially wants to continue to live in a way, in As skin ages, keratinocytes change shape, becom- which they also physically decline. Whereas cultural and ing shorter and fatter; by contrast, corneocytes become technical manipulations have brought about increased bigger due to decreased epidermal turnover. Enzymati- longevity, this has also shaped cultural and technical cally, active melanocytes decrease at a rate of 8%– 20% manipulations so that the side effects of longevity, includ- per decade, resulting in uneven pigmentation in elderly ing wrinkled skin, are increasingly treated. The eternal skin (5) . desire of people around the world is to live longer, to be As time goes by, skin becomes less resistant to shear- young longer, or at least to look younger (3). ing forces and presents an increased vulnerability to insult Aging is a multisystem degenerative process that due to the flattening of the dermo-epidermal junction, involves the skin and the skin support systems, including which occurs as a result of the loss of dermal papillae and the bone, cartilage, and subcutaneous compartments (4) . the reduced interdigitation between layers. This flatten- However, skin transformations are the most perceptible ing begins in the sixth decade (6) . The smaller contiguous surface between the two layers also creates a reduced cellular supply of nutrients and oxygen, leading to an increased *Corresponding author: J é ssica Eleonora Pedroso Sanches risk of dermo-epidermal separation, a process that may Silveira, Rod. Anhanguera, s/n, Km 30, 5 Polvilho, Cajamar, SP 07750-000, Natura, Sao Paulo, Brazil, explain the mechanism by which wrinkles form (8) . E-mail: [email protected] Inside the dermis, many changes also occur. For D é bora Midori Myaki Pedroso: Natura, Sao Paulo, Brazil example, the amount of glycosaminoglycans in the 2 Silveira and Pedroso: UV light and skin aging dermis declines with old age. The amount of hyal- changes in nail plate and there are fewer glands in aged uronic acid, elastin and collagen decreases as they are skin (3) . produced by fibroblasts, whose number also declines. In women, estrogen levels strongly influence skin Indeed, aging is inevitably associated with a decrease in integrity, that is, falling levels in midlife contribute to collagen turnover (due to a decrease in fibroblasts and earlier signs of aging. Furthermore, intrinsic aging pro- their collagen synthesis) as well as elastin. Elastin also ceeds at different rates in all organisms at genetically has higher degree of calcification in aged skin, with an determined pace; this is caused primarily by the buildup associated degradation of elastin fibers. In this case, of reactive oxygen species (ROS) as a by-product of cel- collagen crosslinks stabilize, whereas collagen bundles lular metabolism. ROS, in turn, cause damage to criti- become disorganized. The loss of molecular integrity of cal cellular components like membranes, enzymes, and the dermis leads to increased rigidity, decreased torsion deoxy ribonucleic acid (DNA) (5) . extensibility, and diminished elasticity, eroding faster in There is a great effect of ethnicity on aging, and it women than in men, with a concomitant increase in vul- is primarily related to differences in pigmentation. High nerability to tear-type injuries (5) . levels of pigmentation are protective with regards the Cutaneous aging is a mix of intrinsic aging (due to cumulative effects of photoaging, with African Americans inherent genetics) and extrinsic aging (due to environ- showing little cutaneous difference between exposed mental conditions like solar exposure) (7, 9) . However, the and unexposed sites (11) . Increased innate pigmentation interactions between chronological and photo-induced is related to ultraviolet (UV) damage protection, includ- aging are complex, and the quantification of only the ing less collagen decrease and DNA damage in darker- effect of sun-exposure is difficult to obtain. Hence, a study skinned people (13) . clinically quantified the effect of sun exposure on facial aging in terms of the appearance of new specific signs or in terms of increasing the classical signs of aging. This Extrinsic aging study seems to confirm that pigmentation heterogeneity is a pure photoaging sign, whereas sagging of tissues is Extrinsic skin aging process is characterized by striking essentially a result of chronological aging. Vascular dis- morphologic and physiologic changes that generally lead orders could be considered a precursor of future photo- to a premature aging of the skin. Prominent manifesta- aging. The appearance of wrinkles and skin texture are tions of the extrinsic skin aging process are coarse wrin- influenced by both extrinsic and intrinsic aging, depend- kles, solar elastosis, and pigment irregularities. These ing on the behavior of the individual and the amount of signs superimpose the intrinsic skin aging signs at chroni- sunlight to which he or she has been exposed (10) . cally exposed areas of the body (12) . Extrinsic factors are, to varying degrees, controllable and include exposure to sunlight, pollution or nicotine, Intrinsic aging repetitive muscle movements like squinting or frowning, and miscellaneous lifestyle components, including diet, Intrinsic aging of the skin occurs inevitably as a natural sleeping position, and overall health (14) . Repetitive facial consequence of physiological changes over time at vari- movements actually lead to fine lines and wrinkles. When able yet inalterable genetically determined rates (11) ; it we use a facial muscle, a groove forms beneath the surface is also characterized primarily by functional alterations of the skin, which is why we see lines forming with each than by gross morphological changes (12) . facial expression. As skin ages and loses its elasticity, the Within the skin, collagen production slows down and skin stops springing back to its line-free state, and these elastin has a bit less spring. Dead skin cells do not shed grooves become permanently etched on the face as fine as quickly, and turnover of new skin cells may decrease lines and wrinkles. When the skin elasticity declines in slightly. Although these changes usually begin in the middle age, the effects of gravity become evident. Gravity 20s, the signs of intrinsic aging are typically not visible causes the tip of the nose to droop, the ears to elongate, for decades (4) . The clinical manifestation of intrinsic the eyelids to fall, the jowls to form, and the upper lip to aging includes xerosis, laxity, wrinkles, slackness, and disappear as the lower lip becomes more pronounced. the appearance of a variety of benign neoplasms like seb- Resting your face in the same way every night for years orrheic keratosis and cherry angioma. At the same time, eventually also leads to wrinkles. As a person ages, sleep hair becomes depigmented, terminal hair converts to wrinkles become etched on the surface of the skin and no vellus hair, and loss of hair is increased. There are also longer disappear (4) . Silveira and Pedroso: UV light and skin aging 3

Environmental stressors Smoking causes skin damage primarily by decreasing capillary blood flow to the skin, which, in turn, creates Terrestrial organisms are chronically exposed not only to oxygen and nutrient deprivation in cutaneous tissues. It has natural environmental stress factors like UV and ozone been shown that those who smoke have fewer collagen and

(O3 ), but also to pollutants of anthropic origin (15) . Indus- elastin fibers in the dermis, which causes skin to become trialization changed our lifestyle and new habits have slack, hardened, and less elastic. In addition, constriction of developed that challenge the skin, including smoking, the vasculature by nicotine may contribute to wrinkling (11) . pollution, usage of tanning beds, unhealthy food and bev- erages, sedentary lifestyle, and insufficient sleep (16) . The major mechanism by which environmental insults Air pollution exert a detrimental effect on the skin is through the generation of oxidative stress, which overwhelms the skin’ s Air pollution represents another environmental threat to defenses by quickly depleting the enzymatic (glutathione which millions of humans worldwide are exposed. The peroxidase, glutathione reductase, superoxide dismutase, skin is in direct contact with various air pollutants, and catalase) and nonenzymatic (vitamin E, vitamin C, and thus, the association between air pollution and skin dam- glutathione) antioxidant capacity. Free radicals and ROS aging effects leading to skin aging is likely (12) . interact with lipid-rich plasma membrane and initiate the A recent epidemiological study discovered a direct so-called lipid peroxidation reaction cascade. ROS also link between airborne particulate matter (PM) exposure stimulate the release of pro-inflammatory mediators from and the occurrence of prominent skin aging signs, espe- a variety of skin cells. Skin inflammation leads to skin infil- cially pigment spots and wrinkles (18) . One major mecha- tration by activated neutrophils and other phagocytic cells nism by which ambient PM exerts its detrimental effects that generate further free radicals (both reactive oxygen and is through the generation of ROS. Furthermore, particles nitrogen species), thus establishing a vicious circle (15) . can serve as carriers for organic chemicals and metals that Oxidative stress initiates complex biologic processes are capable of localizing in the mitochondria and generat- in various layers of the skin, which can result in transient ing ROS directly in mitochondria leading to skin aging by or permanent genetic damage, activation of transcription mitochondrial damage (12) . factors and signaling pathways that are involved in cell growth, as well as in differentiation and degradation of Ozone the connective tissue of the dermis (15).

Ozone (O3 ) formed from chemical reaction between UV and O , is a gaseous oxidant that can induce oxidative stress Smoking 2 in cutaneous tissue. In fact, although O3 is not a radical species per se, its effects are mediated through free radical In 1969, Harry Daniell recognized that smokers look older reactions. It is generally accepted that its noxious effects are than non-smokers, and the association between smoking a consequence of biomolecule oxidation, with consequent and skin wrinkling was reproduced in various epidemio- ROS generation, or via a cascade of bioactive nonradical- logical studies. It has been further elucidated that smoking molecules like aldehydes (lipid peroxidation products) (15) . is an independent skin aging-inducing environmental Some studies have already investigated the effects of factor (similar to the effect of sun exposure), and that O on murine cutaneous tissue, providing evidence that O smoking is multiplicative or additive (12) . A study carried 3 3 is capable of affecting the integrity of the skin as a strong out on twins estimated that 10 years of smoking difference oxidative agent. Furthermore, it can induce the expression corresponds to a 2 ½ year-older appearance (17) . of matrix metallopeptidase MMP-9 in murine skin, thus Cigarette smoke (CS) is a highly complex aerosol com- indicating a role in matrix remodeling (12). posed of several thousand chemical substances (gas and the particulate phase). The presence of high levels of pro- oxidants (e.g., free radicals) in smoke is well documented. UV radiation It is estimated that gas-phase smoke contains more than 1014 low molecular-weight carbon- and oxygen-centered UV radiation is a classical and probably the most impor- radicals per puff. In addition, CS contains up to 500 ppm tant factor responsible for skin aging. There are many nitric oxide (NO), which slowly undergoes oxidation to studies on this subject, some of which are presented nitrogen dioxide (NO2 ) (15) . below. 4 Silveira and Pedroso: UV light and skin aging

UV light and skin aging disease, auto-immune conditions, diabetes, cancers, infections and neurodegenerative disease (27, 28) . Earth is constantly irradiated by light photons coming from the sun; 56% are infrared light photons (wavelength, 780 – 5000 nm), 39% is visible light (400 – 780 nm), and 5% is UV light (290 – 400 nm) (19) . Deleterious effects of sun radiation on skin Radiation in the UV region is divided into UVA (320– 400 nm), UVB (280– 320 nm), and UVC (100– 280 nm) Meanwhile, biological research has also unveiled the (20) . The UVC radiation is screened out by the oxygen in deleterious effects of sun radiation on the skin (29) . Bio- the atmosphere, and most of the UVB is screened out by logical and clinical consequences of sun exposure range the ozone layer (21) . However, given the human-induced from immediate sunburn reaction and tanning to long- damage to the protective O3 layer, increasing amounts of term effects like photoaging (7, 11, 30) , photocancer (19, UVB radiation have now reached the Earth ’ s surface (15) . 30), hyperpigmented lesions (19) , verrucous papules, and Many factors contribute to this phenomenon, includ- telangiectasia (31) . In these processes, two skin compart- ing solar zenith angle, season, time of day, hemisphere, ments are affected, namely, the epidermis and the dermis latitude, altitude, clouds, air pollution, surface reflec- (30) . In addition, UV light has a profound effect on the tions, and the stratospheric ozone (21) . For every 300 m eyes. Every year, approximately, 3 million people lose of elevation, there is an increase of 4% of UV radiation their sight because of UV-related damage like cataracts, that reaches the surface, whereas for every degree of thus highlighting the need to incorporate photoprotective decrease in latitude, there is a 3% increase in the trans- measures for the care of the eyes (19) . mission of UVB rays (22) . Moreover, each person ’ s UV dose The effects of sunlight on the skin are profound, and varies depending on avoidance (staying indoors), seeking are estimated to account for up to 90% of visible skin shade from trees and shade or protection from buildings, aging (11) . In a review, Ichihashi (2009) pointed out that awnings, umbrellas, and other sources (e.g., clothing, the photoaged characteristics appear to differ between hats and sunscreens) (21) . racial phenotypes or pigmentary groups. It is commonly When light shines on the skin, several processes take held that lighter-skinned people tend to manifest photo- place. Light can be reflected, scattered, and transmitted aging by wrinkles, whereas those of Asian ethnicities onto the skin and then remitted, i.e., sent back out to exhibit pigmented spots (solar lentigines) rather than the surface. All of these processes have an effect on how wrinkles. The severity of photoaging in any case depends much energy enters the skin and is able to react with the on cumulative sun exposure, and is usually most deter- tissue (2) . mined by occupation and lifestyle. Corneocytes in sun-exposed areas become pleomor- phic with increasing anomalies: retention of nuclear rem- Benefits of sun radiation on skin nants, loss of lines of overlap, and roughening of border edges. In addition, UV radiation alters the skin ’ s immune Skin exposure to UV radiation has beneficial effects for the function systemically. Epidermal thickness increases, human body, e.g., in vitamin D3 formation, or in a curative then decreases, with an eventual loss of epidermal polar- application in combination therapy for skin diseases like ity (orderly maturation) and increased atypia among psoriasis (15, 21) and endorphins production (23) . Vitamin individual keratinocytes (11) . Histopathologically, aged D is produced in skin by the conversion of 7-dehydro- skin undergoes progressive disorientation of dermal col- cholesterol in the epidermis to pre-vitamin D, using the lagen and elastic fiber bundles (32) . In photoaged skin, energy provided by UVB radiation. Thermal conversion at there can be a significant increase in space between fiber body temperature creates the stable form, vitamin D (24) . bundles, thinning of fibers and increased disorganization Approximately 90% of synthesized vitamin D is derived of fiber proteins (31) . from casual exposure to sunlight (25) . Given that the amount of energy is inversely pro- It is already established that vitamin D plays a key role portional to the wavelength, UVB delivers more energy in skeletal health in young and elderly adults. An updated than UVA. Thus, short wavelength radiations in the UV review of the literature emphasizes that adequate levels range have higher energy and are potentially more dam- of vitamin D are needed to prevent osteoporosis, falls, aging (16) . However, UVA has a higher penetration rate and fractures in the elderly population (26) . Emerging and reaches the deepest epidermal layers, whereas UVB data also point to the role of vitamin D in cardiovascular affects primarily epidermis and papillary dermis (33) . The Silveira and Pedroso: UV light and skin aging 5 effects of UVA and UVB radiation of photoaging process photoaging, promotion of carcinogenesis, and influence will be presented in more details ahead. on mitochondrial integrity. However, it is poorly absorbed Within the last decade, it has been reported that by usual skin chromophores like melanin and is too wavelengths beyond the UV spectrum, especially visible weak to directly affect DNA. Indeed, we still do not know light and infrared radiation, contribute to skin damage in which one is most important and to what extent these general and photoaging of human skin in particular (34) . mechanisms, globally and individually, contribute to skin Visible light penetrates deeply into biological tissues and changes with aging. As is the case for visible light, the about 20% reaches the hypodermis. Some recent studies biological relevance of the effects of IR in relation to UV have revealed that visible light affects skin physiology needs to be clarified (16). in many ways, and this is already changing the way we are looking at light. Similar to what is seen with UVA, irradiation of skin with visible light has been reported to Clinical and molecular aspects of (16) generate ROS following photon-induced activation photoaging of endogenous photosensitizers, induce inflammatory cytokines (IL-1, IL-6, IL-8, GM-CSF), increase the expression of matrix-degrading enzymes (MMP-1 and MMP-9) in Clinical manifestation of photoaging human epidermal equivalents, affect DNA through the formation of oxidized DNA bases, and induce pigment dark- Clinical signs of aging are widely described in the litera- ening in subjects with darker skin (Fitzpatrick type IV – V). ture. Jackson (35) has described the differences between In addition, visible light is suspected of being an skin changes brought on by age and skin damaged by aggravating factor in melasma (16) . habitual exposure to sunlight to provide a guide when Infrared (IR) has the lowest energy but comprises examining patients, thus allowing physicians to give around 56% of the solar spectrum reaching human skin. appropriate counsel ( Table 1) (35) . As UV light, IR is divided into IRA (700– 1400 nm), IRB Despite the fact that it is difficult to quantify the sun’ s (1400 – 3000 nm), and IRC (3000 nm – 1 mm). IRB and IRC effect on skin aging, in a study by Flament et al. (10) , it do not penetrate the skin very deeply, but IRA does (16) . has been suggested that pigmentation heterogeneity Infrared A is able to penetrate through all three layers of and vascular disorders are more related to photoaging, the skin, namely, the epidermis, dermis, and subcutis (12) . whereas tissue sagging is a result of chronological aging. IR exposure appears to have non-negligible effects Wrinkles and skin texture are both influenced by intrin- on skin physiology that are mediated through various sic and extrinsic factors (10) . However, clinical signs may molecular mechanisms, including the generation of ROS vary in different parts of the world. Chung et al. (36) have within the skin, promotion of unbalanced gene expres- suggested that wrinkling is more common than hyper- sion of matrix metalloproteinase (MMP), decreased col- pigmentation in Asians. In addition, women show more lagen gene expression in vitro and in vivo, angiogenesis, wrinkles than men. It is probably due to the fact that skin

Table 1 Comparison between clinical signs in intrinsic aging and photoaging (35) .

Structure Intrinsic aging Photoaging

Epidermis Thin Keratosis: solar (actinic), cheilitis, and disseminated superficial actinic porokeratosis Dermis Thin, inelastic, wrinkled Yellowish-brown dotted and plaquelike thickening (solar elastosis), pseudocicatrix, elastotic nodules of the pinna Hypodermis Fold formation None Blood vessels Cherry angiomas, venous lakes Diffuse telangiectasia, erythema, brown pigmentation on side of neck, Bateman’ s (solar) purpura Melanocytes Solar lentigo (flat sebohrreic keratosis) Mottled irregular areas of hypopigmentation and hyperpigmentation/Brown solar keratosis Hair Gray, alopecia None Sebaceous glands Senile sebaceous hyperplasia Solar comedones, nodular cutaneous elastoides Ecrine glands Dry skin None Nails Splitting into layers distally and linear striations None 6 Silveira and Pedroso: UV light and skin aging collagen content decreases due to hypoestrogenism after of this substance in the incidence of skin cancer. Eumela- menopause (36) . nin serves as a physical barrier for UV irradiation and is Uneven pigmentation is one of the major changes a known free radical scavenger. However, the deleterious in the gross morphologic characteristics of the aging effect of melanin has also been described, as it presents skin and is much more marked in sun-exposed areas. In toxic properties after UV exposure and reacts with DNA. the epidermis, melanin pigments are good indicators of Furthermore, pheomelanin may generate hydrogen perox- photoaging. UV radiation plays a major role in the induc- ide and superoxide anions as well as increase histamine tion of melanocyte aging and may severely damage the release (39) . melanocyte system of the skin, resulting in both hyper- Solar elastosis is considered a biomarker for cumula- melanotic and hypomelanotic lesion (37) . tive UV exposure and its risk increased substantially with Coelho et al. (38) have studied the effects of repeti- age. Data suggested that more men present solar elasto- tive UV exposure on human skin, suggesting that there sis than women and it is related to the exposed areas. It is great variability in the constitutive levels of skin pig- has been demonstrated that solar elastosis is strongly mentation as well as in the ability to increase pigmenta- associated with cumulative lifetime site-specific UV dose; tion in response to UV. The pigmentary response UV is however, no link between sunburn and solar elastosis has determined to a large extent by constitutive pigmentation yet to be identified (40) . and is more pronounced with darker skin color. There are four distinct stages in the responses related to pigmentation: the first step termed immediate pigment darkening Photoaging mechanisms (IPD), which occurs after minimal UV exposure; persistent pigment darkening (PPD), which occurs after hours or Photoaging refers to the mechanisms involved in sun days of UV radiation; delayed pigmentation (DP), which damage superimposed on intrinsically aged skin. Molecu- results in increased melanina; and finally, long-lasting pig- lar changes in extrinsic aging involve an augmentation of mentation (LLP), which results from prolonged activation the alterations in chronological aging. Two main defense of te pigmentary system. Coelho et al. also demonstrated mechanisms have been developed to protect against the that melanocyte density and skin pigmentation increase damaging effects of UV: epidermal thickening and the after repetitive UV exposure. Furthermore, long-term stimulation of melanin synthesis (11) . effects of UV can persist for years, as complete turnover According to Pattison and Davies (41) , UVR can of the epidermis usually occurs every 4– 5 weeks. However, mediate damage through direct absorption of the incident the mechanism underlying how the pigmentary system light by the cellular components and through photosensi- remains activated for years later should be studied in more tization mechanisms; such mechanisms are related to elec- detail to provide more insights into abnormal hyperpig- tron transfer and hydrogen abstraction processes to yield mentation in UV-related pigmentary diseases (38) . free radicals (Type I) or energy transfer with O2 to yield the Despite the studies mentioned above, the complex reactive excited state, singlet oxygen (Type II) (41) . mechanisms that lead to pigmentation are still not fully The first mechanism by which UV radiation initiates understood; furthermore, the complex relationship molecular responses in skin is via ROS, through endog- between pigmentation and UV exposure remains contro- enous enzymatic and nonenzymatic protective antioxi- versial. The literature suggests that UV-induced DNA repair dants. If the intracelular mechanisms (e.g., antioxidant and damage involve initiation of signals that induce mel- and repair processes) are working properly, ROS usually anogenesis after UV irradiation, but the chromophores for cause little harm. However, they are responsible for oxida- melanogenesis have not been yet completely established. tive stress, in which there is an imbalance between their Studies have demonstrated that the spectrum that leads generation and the antioxidant defense activity, leading to tanning is the same as that which induces erythema, so to cell damage and death. According to the Free Radical that it is similar to the typical DNA photoproduct (CPD); Theory of Aging, in aged skin, endogenous antioxidative moreover, UV-exposed melanocytes increase DNA repair and repair mechanisms are no longer effective and ROS and the melanin content. tend to increase (42, 43) . It is known that a mix of carotenoids, oxy-/deoxy- Rhie et al. (44) investigated the activities of four anti- hemoglobin, and different types of melanin and their oxidant enzymes, superoxide dismutase (SOD), catalase, distribution in melanosomes determine the skin color. glutathione peroxidase (GPx), and glutathione reductase Brenner and Hearing (39) have already reviewed the role (GR), along with four antioxidant molecules, namely, alpha- of melanin in UV-exposure and described the importance tocopherol, ascorbic acid, uric acid, and glutathione during Silveira and Pedroso: UV light and skin aging 7 the intrinsic aging and photoaging processes. They found UV exposure, the expression of MMP family is induced, that the activities of SOD and GPx did not change during the leading to collagen degradation. aging and photoaging processes, whereas the catalase activ- Fisher et al. (50) have demonstrated that at least three ity became significantly higher and lower in the epidermis different MMPs in human skin are increased with UV and dermis, respectively, of photoaged and naturally aged radiation: interstitial collagenase (MMP-1), stromelysin-1 human skin in vivo compared with young skin. In addition, (MMP-3), and 92kDa gelatinase (MMP-9). The combined antioxidant molecule levels are decreased after UV expo- actions of these three MMPs are capable of degrading sure. Further, the induction and regulation of endogenous most of the proteins that comprise the dermal extracellu- antioxidant defense mechanisms could offer a good strategy lar matrix (50) . Meanwhile, Quan et al. (51) have shown for aging and photoaging treatment and prevention (44) . that MMP-1, -3 and -9 are primarily induced in the epider- Through ROS generation, UVA causes DNA photoda- mis keratinocytes after UV exposure of the skin. However, mage, which is one of the most important acute effects dermal cells, through the release of growth factors or of UV irradiation. UVA is related to production of super- cytokines, may also play a role in the epidermal produc- oxide anion, hydrogen peroxide and singlet oxygen, tion of MMPs (51) . whereas UVB induces base structural DNA damage, as it UV irradiation decreases procollagen mRNA expres- is absorbed directly by DNA (45, 46) . sion in the dermis and decreases collagen amounts, induc- The cellular response to UV radiation involves multi- ing wrinkle formation; however, further studies related to ple and specific signal transduction pathways and tran- the impact of UV irradiation on dermal collagen protein scription factors. L ó pez-Camarillo et al. (47) reviewed synthesis rates are necessary (52) . these specific signal transduction pathways and tran- Photoaging also leads to remodeling of the dermal scription factors, describing the role for p38, MAPK, JNK, extracellular matrix. The effect of repetitive UVB irradia- ERK1/2, and ATM kinases in the response network to UV tion on dermal hyaluronic acid (HA) has been studied, and exposure, as well as the participation of NF- κ B, AP-1, and it involves several mechanisms, including the reduction of NRF2 transcription factors in the control of gene expres- dermal HA, down-regulation of HA enzymes, regulation sion after UV-irradiation (47) . of HA expression in skin fibroblasts in vitro, supression Through ROS generation, Protein Kinase C (PKC) iso- of TGF-beta1- and TbetaR-II expressions, and decreased forms are also involved in skin photoaging. Bossi et al. fibroblast proliferation (53, 54) . (48) reported that the process wherein low doses of UV Aside from all mechanisms einvolving inflammation, radiation generate ROS is regulated by PKC delta and not oxidation and pigmentation, a recent work has elucidated by PKC alpha (48) . the involvement of telomere-based signaling after UV- In keratinocytes, the down-regulation of the pigmen- exposure. Intrinsic aging is controlled by progressive tel- tary effect of UV radiation occurs, involving increased omere shortening, and this same effect can happen after synthesis of the cytokines interleukin-1 (IL1) and tumor UV irradiation, damaging DNA and accelerating telomere necrosis factor alpha (TNF-alpha), whereas in the melano- shortening. Aging and photodamage appear to share a cytes, these factors decrease the proliferation and tyrosi- common final pathway, which involves signaling through nase activity. The prostaglandins D2, E2, and F2-alpha p53 following the disruption of the telomere. These find- are increased in the skin after UV radiation, whereas ings suggest the need to protect from UV damage, with tel- prostaglandins E2 and F2-alpha increase the dendricity of omeres as new targets for preventing photoaging (55, 56) . melanocytes, the effect of which is involved in skin pig- Overall, scientific progress in understanding the mul- mentation as it facilitates the transfer of melanosomes to titude of mechanisms induced by UV-irradiation could keratinocytes. lead to specific targets for the prevention and control of Collagen originates from dermal fibroblasts and is reg- UV-induced aging process. ulated by the transformation of growth factor (TGF-beta) and activator protein (AP-1). TGF-beta is responsible for collagen formation, whereas AP-1 acts through the up-reg- Photoprotection ulation of MMPs, thus causing collagen breakdown (49) . UV irradiation changes the dermal collagen through the stimulation of collagen breakdown and inhibition Sun filters of procollagen biosynthesis, causing loss of collagen content. This process is mediated by MMP expression. Recent advances in photoaging have given rise to new In normal skin conditions, MMPs are low. However, after opportunities of preventing or treating this process. 8 Silveira and Pedroso: UV light and skin aging

These approaches include novel antioxidants and new With the development of nanotechnology, there has compounds. To minimize the deleterious effects of UV been a growth in the application of nanoparticles for drug radiation, photoprotective measures should be adopted. delivery systems, antibacterial materials, cosmetics, and Currently, there are various componds with photoprotec- electronics. Nowadays, almost all UV filters are available tive properties ranging from antioxidants to plant extracts in nanoforms. As they do not have to penetrate skin in to DNA repair enzymes. However, in order to permit new order to protect it, sunscreens have become more opaque. approaches to modulate skin pigmentation, there is a In order to solve this cosmetic drawback, nanotechnology need to gain better understanding of the photoprotective for sun filters has been developed. In the case of nanoma- properties of melanin and contributions of melanocytes to terials, a deep physicochemical approach could help new cancer. formulations display a balance between safety and effec- Active ingredients for photoaging, considering protec- tiveness because safety also concerns the physicochemi- tion against different mechanisms and antioxidant activi- cal properties of UV filters to be taken up by the skin in ties, have already been described (7) . Sunscreens are UV both the absence and presence of light. However, there is radiation-absorbing chemicals that protect the skin and lack of safety data concerning the toxicological properties attenuate the effect of UV radiation on the skin, preclud- of these compounds, and no occupational or environmen- ing sunburns and protecting people from serious skin tal exposure limits have yet to be established (60, 61) . damage. They are selected and tested for their ability to A sunscreen SPF measures how much the product prevent erythema. In addition, sunscreens must be pho- shields the sun ’ s shorter-wave UVB rays (UVB radiation), tostable and must have the ability to dissipate the energy which can cause sunburn. SPF varies from 8 to 100+ and absorbed efficiently through photophysical and photo- it is a controversial issue. When using sunscreen, the rela- chemical pathways, which rule out the ROS and other tionship between the applied amount of sunscreen and harmful reactive intermediates. They should not pen- SPF should be considered. The US FDA and Cosmetics etrate the skin, and should not be transported into the Europe (former COLIPA) recommend 2 mg/cm2 of product human cells where they can cause deleterious damage application, based on the observation that lower amounts to DNA. Despite the fact that they are widely use, further reduce the homogeneity of the protective film on the skin data related to the safety and efficacy of sunscreens are as a result of irregularities of the skin surface (62, 63) . needed. However, the amount of the sunscreen applied is Ideal sunscreening agents should be safe, chemi- often inadequate, and the protection achieved by the user cally inert, nonirritating, nontoxic, photostable, and must is lower than that shown in the product label. Recent data provide complete protection of the skin against damage in the literature have reinforced the need to promote the from solar radiation. They should be formulated in a cos- appropriate use of protection against UV radiation, con- metically acceptable form and ingredients should remain sidering the correct amount and frequent reapplication on the upper layers of the skin. In the US, sunscreen pro- (64) . duction is regulated by the FDA; meanwhile, in European Osterwalder and Herzog (65) have described the rela- countries and in Brazil, among other countries, there are tionship between high SPF values and protection against efforts to regulate the maximum concentration of use. UV, meaning that higher SPF provides more protection, as Sunscreens are divided into physical and organic com- the UV radiation doses are smaller in higher SPF condi- pounds (57) . tions. This issue has already been under discussion, but

Titanium dioxide (TiO2 ) and Zinc oxide (ZnO) are in addition to the SPF, data on the water resistance, UVA the most used, as they block UVB/UVA sunlight through protection, and photostability should be considered for reflection and scattering. These mineral compounds are adequate protection (57, 65) . used extensively in cosmetics, including foundations, At present, researchers are developing newer broad- powders, eye shadows and pencils, due to their low poten- spectrum chemical agents that are effective against tial for producing irritant reactions. UVA and UVB rays, including bis-ethylhexyloxyphenol

Different from TiO2 and ZnO, organic filters are classi- methoxyphenyl triazine, methylene bis-benzotriazolyl fied into either UVA (benzophenones, anthranilates and tetramethylbutylphenol, and butyl methoxy-dibenzoyl dibenzoylmethanes) or UVB filters (PABA derivatives, methane. It is challenging to provide cosmetically accept- salicylates, cinnamates and camphor derivatives). They able preparations that are non-stick and water-resistant, are used in combination in order to provide high enough and educate people about following the correct applica- sun protection factor (SPF) protection or broad-spectrum tion instructions. Furthermore, these UV filters should be absorption (58, 59) . compliant to safety and regulatory requirements, so the Silveira and Pedroso: UV light and skin aging 9 industry should consider sensitization reactions, espe- sunscreens because they offer balanced and uniformed cially in those with eczema or photodermatoses as well as protection for both UVA and UVB, which remain constant irritation, following new directions regarding no animal while using the clothes. Furthermore, the degree of protec- testing (57) . tion offered by sunscreens depends on the application of New sunscreen properties like anti-inflammatory and the correct amount of the product. Finally, clothing and hats antioxidant effects have also been described. Another are less costly than sunscreens, and they are devoid of any new approach is the use of active ingredients in cosmetic complications like contact or photoallergic dermatitis (22) . formulations in order to increase SPF. Formulators are The World Health Organization (WHO) mainly recommends using certain ingredients with anti-inflammatory proper- photoprotection by means of clothing for children (69) . ties like a-bisabolol and 18 b-glycyrrhetinic acid. However, A French study analyzed the photoprotection of further data are needed to determine how the biological clothes of different types, color, and thicknesses. Concern- response of the human UV-irradiated skin might vary with ing townwear, jeans, tracksuits, sweatshirts, pullovers the inclusion of specific anti-inflammatory ingredients in and tights turned out to be very photoprotective. They are the sunscreens (66) . able to reach a ultraviolet protection factor (UPF) higher Osterwalder et al. (67) have reviewed the global state than 500. The thickness of the fabric is of great impor- of sunscreens, pointing out the controversies related to tance, so the lowest protection factors (PF = 12) have been high SPF as well as the relationship between UV radiation obtained for the Tex baby blouse and the Domyos T-shirt. and agent protection. Global harmonization should be of These two fabrics are both made of 100% cotton and are concern in order to provide global access to modern UV light-colored (white and pale green, respectively) and are sunscreen technology, performance measurements, and of very different thicknesses (the blouse is practically adequate criteria for good sun protection (67) . twice as thick as the T-shirt); however, their photoprotec- Despite all controversial aspects, the importance of tive effect in the UVB field is the same, which explains the sunscreen usage remains unquestionable. Many epide- importance of how the fabric is woven (69) . miological studies have been conducted to correlate the Sun-protective clothing lines exist and are widely effects of sunscreen use on skin cancer, and more recently available in sporting goods stores and on the Internet. photoaging, but their findings have been mostly unin- These clothing lines offer hats, long-sleeved clothing, etc. formative. Although Iannacone et al. (68) reviewed the and are geared towards patients who work outdoors and available data on the issue, adequate evidence remains are avid outdoor enthusiasts for whom sunscreens might limited, especially related to the prevention of photoag- be less practical to use. The fabrics used in these lines are ing. Sunscreen use alone will not reduce skin cancer and highly engineered and sophisticated materials that confer photoaging, but its cosmetic benefits may be an effec- high levels of sun protection and protect against both UVA tive strategy that can be used by dermatologists, general and UVB. For example, Solumbra, manufactured by Sun physicians, and public health and prevention agencies to Precautions, offers an SPF 30 + and reportedly blocks 97% achieve sun protection for long-term primary prevention of UVA and UVB. Coolibar is another brand of sun-pro- of skin cancers (68) . tective clothing and hats, which provide UPF of 50 + and It has already been established that UVA measure- reportedly blocks 98% of UVA and UVB. UPFs are similar ments in vivo are linked to SPF assessment, and UVA to SPFs but are typically used for devices like clothing and protection should follow what is recommended by fabrics rather than for sunscreen. Clothing lines and other the European commission, which states that UVA-PF/ sun-protective devices endorsed by the Skin Cancer Foun- SPF ≥ 1/3. In addition, the available in vitro UVA methods dation are listed on their website (14) . are currently being harmonized. Other UVA categories UV exposure can also damage the cornea, conjunc- like the Boots 5-star rating with a UVA/UVB ratio > 0.9 go tiva, lens, and retina, resulting in a number of conditions beyond the EU recommendation and are thus closer to collectively named “ ophthalmohelioses ” (22) . Acute injury uniform UVB/UVA protection, which may be regarded as in the eye presents similar features to those on the skin the ideal sunscreen performance (67) . and includes photoconjunctivitis (“ pinkeye ” ), solar kera- titis, and in severe cases, transient loss of vision. Chronic exposure, on the other hand, may result in cataracts and Clothing and glasses macular degeneration the leading causes of loss of vision (19) . Clothing and glasses are the most basic photoprotective Sunglasses can protect the eye from UV damage. Aside tools and, in many aspects, seem to be more effective than from the cosmetic quality, an ideal pair of sunglasses 10 Silveira and Pedroso: UV light and skin aging should block all UV rays but should not sacrifice the trans- are caused by intrinsic and extrinsic factors. Sun radiation mission of visible light. Currently in the US, a standard seems to be the major factor of skin premature aging, and guideline of Z80.3 2008 by the American National Stand- recent papers have demonstrated the importance of UVA, ards Institute (ANSI), is issued to categorize the different UVB, visible light, and infrared in this complex process types of sunglasses according to the degree of shading and evolving the epidermis and dermis. Although the estab- UV absorption profile. ANSI is a nongovernmental and lished role of UVB on vitamin D production has been consensus body. Recently, therapeutic sunglasses have presented, other benefits of solar exposition like photo- been made available, providing protection against UV and protection are essential to avoid premature skin aging and blue light. Coloring must be dark enough to prevent daz- some diseases like skin cancer. Nowadays, there are dif- zling but must not affect color and contrast perception (19) . ferent ways to to seek protection from the sun like wearing topical sunscreens and wearing glasses and clothes that offer UVA and UVB protection. It is possible to have oral Food and photoprotection sunscreens, combination of antioxidants or even probiotics, but further studies to evaluate its efficacy are Recently, several oral sunscreens that provide full-body necessary. coverage have been commercialized. These products contain several active principles that enable different Conflit of interest statement : No conflicts of interest exist. mechanisms to prevent cutaneous sun damage. Most of them possess antioxidant activities, which replenish the normal antioxidant capability of the body after systemic References loss of endogenous antioxidants during UV exposure.

These products include the following: carotenoids, com- 1. Rubinstein RL, Canham S. Aging skin in sociocultural perspec- bination of antioxidants (vitamins C and E), selenium, tive. In: Dayan N, editor. Skin aging handbook: an integrated proanthocyanidins, and dietary botanicals (flavonoids approach to biochemistry and product development. New York: and phenolics). Nevertheless, the efficacy of oral sun- William Andrew Norwich, 2008:4 – 15. screens to prevent photoaging in humans has not been 2. Puizina-Ivi N. Skin aging. Acta Dermatoven APA 2008;17:47 – 52. 3. Binic I, Lazarevic V, Ljubenovic M, Mojsa J, Sokolovic D. Skin assessed in long-term clinical trials (19). ageing: natural weapons and strategies. Evid Based Comple- Probiotics (live microorganisms that confer a health ment Alternat Med 2013;2013:1 – 10. benefit on the host) are most commonly administered 4. Sjerobabski-Masnec I, Š itum M. Skin aging. Acta Clin Croat orally, with the goal of maintaining healthy gut flora 2010;49:515 – 19. by populating the gut with symbiotic bacterial species. 5. Farage MA, Miler KW, Elsner P, Maibach HI. Characteristics of the aging skin. Adv Wound Care 2013;2:5 – 10. Strains of the genera Lactobacillus and Bifidobacte- 6. Waller JM, Maibach HI. Age and skin structure and function, a rium are the most widely used probiotic bacteria. Orally quantitative approach (I): blood flow, pH, thickness, and ultra- ingested Lactobacilli have been shown to protect against sound echogenicity. Skin Res Technol 2005;11:221 – 35. UVR-induced cutaneous immunosuppression in mouse 7. Lorencini M, Brohem CA, Dieamant GC, Zanchin NIT, Maibach HI. models through protection against the suppression of Active ingredients against human epidermal aging. Ageing contact hypersensitivity, decreased epidermal Langer- Research Rev 2014;15:100 – 15. 8. S ü del KM, Venzke K, Mielke H, Breitenbach U, Mundt C, hans cell density and increased IL-10 serum levels, which et al. Novel aspects of intrinsic and extrinsic aging of human may reduce the development of skin tumors. Although no skin: beneficial effects of soy extract. Photochem Photobiol similar human studies have been published, the use of 2005;81:581– 87. probiotics offers a promising new direction in sun protec- 9. Thakur R, Batheja P, Kaushik D, Michniak B. Structural and tion, and this should attract future research (70) . biochemical changes in aging skin and their impact on skin permeability barrier. In: Dayan N, editor. Skin aging handbook: an integrated approach to biochemistry and product development. New York: William Andrew Norwich, 2008:56 – 84. 10. Flament F, Bazin R, Laquieze S, Rubert V, Simonpietri E, et al. Conclusions Effect of the sun on visible clinical signs of aging in Caucasian skin. Clin Cosm Investig Dermat 2013;6:221 – 32. Life expectancy is continuously rising in developed coun- 11. Farage MA, Miler KW, Elsner P, Maibach HI. Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosm Sci 2008;30:87– 95. tries, but no one especially wants to continue to live in a 12. Vierk ö tter A, Krutmann J. Environmental influences on skin way in which they also physically decline. Skin transfor- aging and ethnic-specific manifestations. Dermatoendocrinol mations are the most perceptible signs of aging, and these 2012;4:227 – 31. Silveira and Pedroso: UV light and skin aging 11

13. Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, et al. Mecha- 36. Chung JH, Lee SH, Youn CS, Park BJ, Kim KH, et al. Cutaneous nisms of photoaging and chronological skin aging. Arch Derma- photodamage in Koreans. Influence of sex, sun exposure, smok- tol 2002;138:1462 – 70. ing, and skin color. Arch Dermatol 2001;137:1043 – 51. 14. Helfrich YR, Sachs DL, Voorhees JJ. Overview of skin aging and 37. Castanet J, Ortonne J-P. Pigmentary changes in aged and photo- photoaging. Dermatol Nurs 2008;20:177 – 83. aged skin. Arch Dermatol 1997;133:1296 – 99. 15. ValacchiG, Sticozzi C, Pedorelli A, Cervellati F, Cervellati C, et al. 38. Coelho SG, Choi W, Brenner M, Miyamura Y, Yamaguchi Y, et al. Cutaneous responses to environmental stressors. Ann NY Acad Short- and long-term effects of ultraviolet radiation on the Sci 2012;1271:75 – 81. pigmentation of human skin. J Investig Dermatol Symp Proc 16. Dupont E, Bilodeau D. Beyond UV radiation: a skin under chal- 2009;14:32 – 35. lenge. Int J Cosmet Sci 2013:1 – 9. 39. Brenner M, Hearing VJ. The protective role of melanin against uv 17. Rowe DJ, Guyuron B. Environmental and genetic factors in facial damage in human skin. Photochem Photobiol 2008;84:539 – 49. aging in twins. In: Farage MA, Miller KW, Maibach HI, editors. 40. Thomas NE, Kricker A, From L, Busam K, Millikan RC, et al. Textbook of aging skin. Heidelberg: Springer Berlin, 2010:441– 46. Genes, environment, and melanoma study group. Associations 18. Vierk ö tter A, Schikowski T, Ranft U, Sugiri D, Matsui M, et al. of cumulative sun exposure and phenotypic characteristics with Airborne particle exposure and extrinsic skin aging. J Invest histologic solar elastosis. Cancer Epidemiol Biomarkers Prev Dermatol 2010;130:2719 – 26. 2010;19:2932 – 41. 19. Gonz á lez S, Fern á ndez-Lorente M, Gilaberte-Calzada Y. The lat- 41. Pattison DI, Davies MJ. Actions of ultraviolet light on cellular est on skin photoprotection. Clin Dermatol 2008;26:614 – 26. structures. EXS 2006;96:131 – 57. 20. Hockberger PE. A history of ultraviolet photobiology for 42. Poljsak B, Dahmane R. Free radicals and extrinsic skin aging. humans, animals and microorganisms. Photochem Photobiol Dermatol Res Pract 2012;135 – 206. 2002;76:561 – 79. 43. Pandel R, Polj š ak B, Godic A, Dahmane R. Skin photoaging and 21. Godar DE. UV doses worldwide. Photochem Photobiol the role of antioxidants in its prevention. ISRN Dermatology 2005;76:736 – 49. 2013;1 – 11. 22. Wang SQ, Balagula Y, Osterwalder U. Photoprotection: a 44. Rhie G, Shin MH, Seo JY, Choi WW, Cho KH, et al. Aging- and review of the current and future technologies. Derm Therapy photoaging-dependent changes of enzymic and nonenzymic 2010;23:31 – 47. antioxidants in the epidermis and dermis of human skin in vivo. 23. D ’ orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV radiation and the J Invest Dermatol 2001;117:1212– 17. skin. Int J Mol Sci 2013;14:12222 – 48. 45. Kvam E, Tyrrell RM. Induction of oxidative DNA base damage in 24. Tongkao-On W, Gordon-Thomson C, Dixon KM, Song EJ, human skin cells by UV and near visible radiation. Carcinogen- Luu, Sally E, et al. Novel vitamin D compounds and skin cancer esis 1997;18:2379 – 84. prevention. Dermatoendocrinol 2013;5:20– 33. 46. Sander CS, Chang H, Hamm F, Elsner P, Thiele JJ. Role of oxida- 25. Holick MF. Vitamin D: a millenium perspective. J Cell Biochem tive stress and the antioxidant network in cutaneous carcino- 2003;88:296 – 307. genesis. Int J Dermatol 2004;43:326 – 35. 26. Kannan S, Lim HW. Photoprotection and vitamin D: a review. 47. L ó pez-Camarillo C, Ocampo EA, Casamichana ML, Pé rez-Plasen- Photodermatol Photoimmunol Photomed 2014;30:137 – 45. cia C, Alvarez-S ánchez E, et al. Protein kinases and transcription 27. P é rez-L ó pez FR, Brincat M, Erel CT, Tremollieres F, Gambacciani factors activation in response to UV-radiation of skin: implica- M, et al. EMAS position statement: Vitamin D and postmenopau- tions for carcinogenesis. Int J Mol Sci 2012;13:142 – 72. sal health. Maturitas 2012;72:83 –8. 48. Bossi O, Gartsbein M, Leitges M, Kuroki T, Grossman S, 28. Wacker M, Holick MF. Sunlight and vitamin D: a global perspec- et al. UV irradiation increases ROS production via PKCdelta tive for health. Dermato-Endocrinology 2013;5:51 – 108. signaling in primary murine fibroblasts. J Cell Biochem 29. Kim HH, Lee MJ, Lee SR, Kim KH, Cho KH, et al. Augmentation 2008;105:194 – 207. of UV-induced skin wrinkling by infrared irradiation in hairless 49. Rabe JH, Mamelak AJ, McElgunn PJ, Morison WL, Sauder DN. mice. Mech Ageing Dev 2005;126:1170 – 7. Photoaging: mechanisms and repair. J Am Acad Dermatol 30. Bernerd F, Marionnet C, Duval C. Solar ultraviolet radiation 2006;55:1 – 19. induces biological alterations in human skin in vitro: relevance 50. Fisher GJ, Choi HC, Bata-Csorgo Z, Shao Y, Datta S, et al. Ultra- of a well-balanced UVA/UVB protection. 2012;78(suppl):15 – 23. violet irradiation increases matrix metalloproteinase-8 protein 31. Ichihashi M. Photoaging of the skin: review article. Anti-Aging in human skin in vivo. J Invest Dermatol 2001;117:219 – 26. Medicine 2009;6:46 – 59. 51. Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ, et al. Matrix-degrading 32. Warren R, Gartstein V, Kligman AM, Montagna W, Allendorf RA, Metalloproteinases in Photoaging. J Investig Dermatol Symp et al. Age, sunlight, and facial skin: a histologic and quantitative Proc 2009;14:20 – 24. study. J Am Acad Dermatol 1991;25:751 – 60. 52. Murakami H, Shimbo K, Inoue Y, Takino Y, Kobayashi H. Impor- 33. Hoffmann K, Kaspar K, Altmeyer P, Gambichler T. UV transmis- tance of amino acid composition to improve skin collagen sion measurements of small skin specimens woth special quartz protein synthesis rates in UV-irradiated mice. Amino Acids cuvettes. Dermatol 2000;201:307– 2011. 2012;42:2481 – 89. 34. Grether-Beck S1, Marini A, Jaenicke T, Krutmann J. Photoprotec- 53. Dai G, Freudenberger T, Zipper P, Melchior A, Grether-Beck S, tion of human skin beyond ultraviolet radiation. Photodermatol et al. Chronic ultraviolet B irradiation causes loss of hyaluronic Photoimmunol Photomed 2014;30:167– 74. acid from mouse dermis because of down-regulation of hyalu- 35. Jackson R. Elderly and sun-affected skin. Distinguishing ronic acid synthases. Am J Pathol 2007;171:1451 – 61. between changes caused by aging and changes caused by 54. Calikoglu E, Sorg O, Tran C, Grand D, Carraux P, et al. UVA and habitual exposure to sun. Can Fam Physician 2001;47:1236 – 43. UVB decrease the expression of CD44 and hyaluronate in mouse 12 Silveira and Pedroso: UV light and skin aging

epidermis which is counteracted by topical retinoids. Photo- 62. Brown S, Diffey BL. The effect of applied thichness on sunscreen chem Photobiol 2006;82:1342– 47. protection: in vivo and in vitro studies. Photochem Photobiol 55. Yin B1, Jiang X. Telomere shortening in cultured human dermal 1986;44:509 – 13. fibroblasts is associated with acute photodamage induced by 63. Dale Wilson B, Moon S, Armstrong F.Comprehensive review of UVA irradiation. Postepy Dermatol Alergol 2013;30:13 – 18. ultraviolet radiation and the current status on sunscreens. J Clin 56. Ma HM, Liu W, Zhang P, Yuan XY. Human skin fibroblast telom- Aesthet Dermatol 2012;5:18 – 23. eres are shortened after ultraviolet irradiation. J Int Med Res 64. Schalka S, Reis VM. Sun protection factor: meaning and contro- 2012;40:1871 – 87. versies. An Bras Dermatol 2011;86:507 – 15. 57. Latha MS, Martis J, Shobha V, Shinde RS, Bangera S, et al. 65. Osterwalder U, Herzog B. Sun protection factors: worldwide Sunscreening agents: a review. J Clin Aesthet Dermatol confusion. Brit J Dermatol 2009;161 (Suppl. 3):13 – 24. 2013;6:16 – 26. 66. Couteau C, Chauvet C, Paparis E, Coiffard L. UV filters, ingre- 58. Gasparro FP. Sunscreens, sin photobiology and skin cancer: dients with a recognized anti-inflammatory effect. PLoS One. the need for UVA protection and evaluation of efficacy. Environ 2012;7:e46187. Health Persp 2000;108. 67. Osterwalder U, Sohn M, Herzog B. Global state of sunscreens. 59. Serpone N, Dondi D, Albini A. Inorganic and organic UV filters: Photodermatol Photoimmunol Photomed 2014;30:62 – 80. their role and efficacy in sunscreens and suncare products. 68. Iannacone MR, Hughes MC, Green AC. Effects of sunscreen on Inorganica Chimica Acta 2007;360:794 – 802. skin cancer and photoaging. Photodermatol Photoimmunol 60. Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide Photomed 2014;30:55 – 61. nanoparticles: a review of current toxicological data. Part Fibre 69. Ghazi S, Couteau C, Paparis E, Coiffard LJ. Interest of external Toxicol 2013;15:10 – 15. photoprotection by means of clothing and sunscreen products 61. Smijs TG, Pavel S. Titanium dioxide and zinc oxide nanoparticles in young children. JEADV 2012;26:1026 – 30. in sunscreens: focus on their safety and effectiveness. Nano- 70. Viera MH, Amini S, Huo R, Berman B. What’ s new in natural com- technol Sci Appl 2011;4:95– 112. pounds for photoprotection? Cosm Dermat 2008;21:279– 89.