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Keywords:

  • Asian;
  • dyspigmentation;
  • photoaging;
  • wrinkle

Abstract

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

The aging process of the skin can be divided into intrinsic and photoaging. Clinically, naturally aged skin is smooth, pale and finely wrinkled. In contrast, photoaged skin is coarsely wrinkled and associated with dyspigmentation and telangiectasia. Although the population of Asia is more than half the population of the Earth, no well-designed study has been undertaken to investigate the characteristics of cutaneous photodamage in Asian skin. As Asian skin is more pigmented, the acute and chronic cutaneous responses to UV irradiation seen in brown skin differ from those in white skin. The clinical characteristics of photoaging in Asian skin, such as pigmentary changes and wrinkle patterns, differ from those of Caucasian skin. This review provides an outline of the characteristic features of photoaging on the brown skin of Asians.

Skin aging can be divided into two basic processes, intrinsic aging and photoaging (1). Photoaging describes premature skin aging in chronically photodamaged skin. If habitually sun-exposed skin in the elderly is compared with skin from the sun by clothing, the exposed skin appears more aged. Intrinsic aging is characterized by smooth, dry, pale and finely wrinkled skin. On the other hand, photoaging is characterized by severe wrinkling and pigmentary changes, such as solar lentigo and mottled pigmentation on exposed areas such as the face, neck and forearm (Fig. 1).

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Figure 1.  Skin aging in Asians. Sun-exposed skin showing the characteristics of severe photodamage, i.e., wrinkling, irregular pigmentation, loss of elasticity and dry skin, which is in contrast to the sun-protected skin.

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Although the population of Asia is more than half of the total population of the Earth, the inherent characteristics of Asian skin have not been well investigated as compared with Caucasian white skin. The people of Asia are primarily of Mongolian extraction. The people of Japan, Korea and China appear similar and are difficult to differentiate. All have typical Mongol features and brown skin (2). These three countries account for about one-fourth of the world's population.

Many investigators believe, based on their experiences, that the principal manifestation of photodamage in Asians is pigmentary change rather than wrinkling (3–5). However, to our knowledge, no well-designed study has been undertaken to investigate the characteristics of cutaneous photodamage in Asian skin.

Clinical manifestations of photoaging in Asian skin

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

The clinical characteristics of photoaging in Asian skin, such as pigmentary changes and wrinkle patterns, differ from those of Caucasian skin (6). Ethnic and genetic differences modify skin structure and function, in the brown skins of Asians and the white skins of Caucasians (7). Differences in the clinical manifestations of photoaging may possibly be caused by different habits as related to sun exposure, and different natural defense mechanisms against the effects of chronic exposure to sunlight. Asians such as Korean, Japanese and Chinese traditionally avoid direct sunlight by wearing long-sleeved clothes, carrying umbrellas or by sitting in the shade. Natural defense mechanisms against sun exposure include the production of melanin, thickening of the stratum corneum and the presence of epidermal proteins, such as urocanic acid. The primary difference between Caucasian and Asian skin is attributed to melanocytic function. As Asian skin is more highly pigmented, its acute and chronic cutaneous responses to UV irradiation differ from those of white skin. It has been reported that in the brown skin of the people of Singapore, Indonesia or Malaysia, changes in pigmentation seem to be a more important feature in prematurely aged skin than wrinkling. Skin wrinkling in these populations is not readily apparent until the age of about 50 years, and even then the degree of wrinkling is not as marked as in Caucasian skin (3).

Wrinkles in photoaged skin

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

Photographic scale of wrinkles in Asian skin

An evaluation system for skin wrinkling is necessary in order to quantify the severity of wrinkles in Asian skin. We have developed an eight-point photographic scale for assessing wrinkles in both genders for Koreans (2). Griffiths et al. (4) and Larnier et al. (5) developed similar photographic scales to evaluate the characteristic features of photoaging in female Caucasian subjects, and suggested that their scales should not be used to evaluate photodamage in Far East Asians. These investigators have tried to describe photodamage in each individual by a single score. Because of the difficulty associated with quantifying the different features of photoaging, such as wrinkling and pigmentary changes, in the same individual using a single score, we developed separate grading systems for wrinkling and dyspigmentation for both sexes for Koreans (2).

Our photographic wrinkle scale (Fig. 2) can probably be applied to the populations of other Asian countries, at least to the Japanese and Chinese. As shown in Fig. 2, grade zero represents the absence of wrinkles and grade 7 indicates a severely wrinkled status. The pattern and severity of wrinkling in each gender scale appears to be similar (2). The photographic scales developed provide consistent and reproducible clinical evaluations of wrinkle severity in Koreans, and show good interobserver agreement and intraobserver reproducibility (2). These new photographic scales can be used by clinicians without special training, and they provide a more reliable tool than a written, descriptive scale for assessing photodamaged facial skin (2, 4). This grading system can be used for categorizing groups of photoaged subjects prior to drug therapy. This grading system also allows greater reliability between centers involved in photoaging studies and enables more precise grading.

image

Figure 2.  Photographic scale for wrinkles in Koreans. This scale can probably be applied to the inhabitants of other East Asian countries, but applies particularly to Koreans, Japanese and Chinese. Grade zero represents the absence of any wrinkles and grade 7 indicates a severely wrinkled status. Because the pattern of wrinkling is the same for both Korean genders, this photographic scale can be used for women and men.

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Causes of skin wrinkling and their relative risk in Asian skin

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

Various factors such as genetic background, age, smoking and sun exposure are considered to be independent risk factors of wrinkling in Caucasians. However, the relative risks of each factor on wrinkling in brown Asian skins have not yet been investigated, although they could be expected to differ from those of Caucasians. Recently, we investigated the causative factors of skin wrinkling, their relative risks in the Korean population, and the molecular mechanisms of wrinkle development (2, 6).

Genetic background

Racial differences may dictate the different patterns of skin wrinkling. We found that wrinkling patterns in Asians seem to differ from those of Caucasians (6). Asians have coarser, thicker and deeper wrinkles, particularly on the forehead, perioral and Crow's feet areas. In contrast, Caucasians usually have relatively fine wrinkles on their cheeks and the Crow's feet area (6). The reasons for these differences are unknown and need to be investigated further. However, within a race, some people develop severe skin wrinkling while others develop mild skin wrinkling, although they have the same risk factors. This observation suggests the possibility that there may be wrinkle-associated genes or single nucleotide polymorphism (SNPs) in certain genes, such as collagen, elastin or matrix metalloproteinase (MMP) genes. Further investigations on photoaging-related genes are required to understand such racial and individual differences in terms of susceptibility to skin wrinkling.

Age

Age is of course an important wrinkling risk factor, as has been demonstrated in Koreans (2) and the Japanese (8). After controlling for many variable factors, including gender, sun exposure and smoking, Korean subjects in their sixties were found to have a 12-fold higher risk of wrinkling, and subjects in their seventies a 56-fold higher risk vs. the young (30–59 years) group (2). Many investigators believe that pigmentary changes are the prominent clinical sign of photoaging in Asians, and that wrinkling is late and an inconspicuous feature. Goh (3) reported that wrinkling in Asians is not noticeable until the age of about 50, and that even then its degree is not as marked as in Caucasian subjects of a similar age. However, we found that wrinkling is also a prominent feature of cutaneous photodamage in Koreans of this age (6). Koreans usually do not have wrinkles before 30 years of age. Wrinkles greater than grade 3 (according to our photographic grading system (2)) become apparent from the age of 50, and wrinkles of more than grade 4 were found from the early sixties in males and from the late fifties in females (2).

Smoking and skin wrinkling

It is known that smoking causes premature aging and wrinkling of the face in Caucasians (9–12), but plays no role in the wrinkling of black skin (13). Prominent facial wrinkling is significantly more common among smokers than among nonsmokers. In Caucasian white skin, premature wrinkling was found to increase with the number of smoking pack-years. Heavy Caucasian smokers (>50 pack-years) were found to be 2.3–4.7 times more likely to be wrinkled than nonsmokers (10, 11). When smoking and excessive sun exposure coexisted, their effects on the wrinkling of white skin were found to be synergistic. As in white skin, in the brown skin of Koreans the prevalence odds ratios of wrinkling associated with 30 and 50 pack-years of smoking were 2.8 and 5.5, respectively, after controlling for age, gender and sun exposure (2). The combined effects of sun exposure and smoking were synergistic and presented an 11-fold increased risk of wrinkling compared to nonsmokers in a less sun-exposed group (2). Yin et al. (8) also reported that subjects, admitting a high number of pack-years (>30 pack-years) and sun exposure (>2 h per day) in the Japanese population, had a 22 times higher risk of developing more severe skin wrinkling than those who had never smoked and had lower sun exposure levels (<2 h per day) at the same age. These reports suggest that cigarette smoking is an independent risk factor for the development of wrinkles in Asians, including Koreans and Japanese, as in the Caucasians. Furthermore, the detrimental effects of smoking act synergistically with the effects of aging and sun exposure in Asians.

Ultraviolet light

It is well known that the UV component of sunlight can cause and accelerate photoaging in Caucasians. The pigmented skins of Asian and Black people are believed to protect the skin from acute and chronic UV damage. There is also a strong association between sun exposure and the development of wrinkling in Asian skins. After controlling for age and gender, it was found that a sun exposure of more than 5 h per day was associated with a 4.8-fold increased risk of wrinkling vs. those with 1 or 2 h of sun exposure in the Korean population (2).

Molecular mechanisms of UV-induced wrinkle formation in human skin in vivo

Acute UV effects

Alterations and deficiencies of collagen, the major structural component of skin, have been suggested to be a cause of the skin wrinkling observed in photoaged and naturally aged skin (14, 15). The dermis contains predominantly type I and type III collagen, elastin, proteoglycans and fibronectin. Dermal fibroblasts synthesize individual polypeptide chains of types I and III collagen as precursor molecules, called procollagen (16). During the formation of insoluble collagen fibrils, specific proteases cleave the carboxy and amino terminal domains of procollagen, forming pN collagen (a procollagen from which the carboxy terminal propeptide has been cleaved) and pC collagen (a procollagen from which the amino terminal propeptide has been cleaved), respectively. Because type I and type III procollagen, pN collagens and pC collagens are precursor molecules of mature collagen, their levels generally reflect the level of collagen biosynthesis (17, 18). Also, since collagen fibrils and elastin are responsible for the strength and resilience of skin (19), their disarrangement during photoaging causes the skin to appear aged.

Recently, it was suggested that excessive matrix degradation by UV-induced MMPs secreted by various cells, including keratinocytes, fibroblasts and inflammatory cells, contributes substantially to the connective tissue damage that occurs during photoaging (20–22). UVB is known to induce the expressions of MMP-1, -3 and -9 in the normal human epidermis in vivo (20), and UVA is known to induce the expression of MMP-1 by dermal fibroblasts in vivo, and the expressions of MMP-1, -2 and -3 in culture (23). These results indicate that collagen deficiency in chronically photodamaged skin may result from the increased, repetitive degradation of collagen by UV-induced MMPs.

The following model of UV-induced photoaging seems to be the most widely accepted (14). UV irradiation of the skin induces the expressions of AP-1-driven genes, including MMPs, such as interstitial collagenase and 92 kDa gelatinase, through signal transduction pathways, which involve a series of kinases. These MMPs degrade collagen, by causing chronic and repetitive damage, which finally results in collagen deficiency, and leads to wrinkling.

Collagen metabolism in aged and photoaged human skins in vivo
MMP expression

Fisher et al. (14, 20) proposed that MMP-mediated collagen destruction accounts for a large part of the connective tissue damage that occurs during photoaging. The expression of MMP-1 protein in the dermis of sun-exposed and sun-protected skin of elderly subjects is known to differ (21). In young skin, the level of MMP-1 expression in the upper-inner arm and forearm skin is similar. The expression of MMP-1 protein in sun-protected skin is higher in aged skin than in young skin. On the other hand, photodamaged skin of the elderly shows higher MMP-1 protein expression than the intrinsically aged skin in the same individual (21).

MMP-2 and MMP-9 expressions are also higher in aged skin than in young skin (15, 21). Sun-damaged forearm skin shows significantly higher levels of active MMP-2, proMMP-2 and MMP-9 than intrinsically aged skin in the same individual. Thus, the resulting higher expression of MMPs in photoaged skin may cause severe collagen deficiency and wrinkling.

In the case of natural aging, the collagen content in the dermis decreases approximately 1% per year throughout adult life. The molecular mechanisms of collagen deficiency associated with natural skin aging are also the result of elevated MMP expression and a concomitant reduction in collagen synthesis (15). With increasing age, MMP levels become higher and collagen synthesis lower in sun-protected human skin in vivo (15, 21).

Procollagen expression

To understand the molecular mechanisms of severe wrinkling in photoaged skin, Chung et al. (21) compared the collagen metabolism of photoaged skin with intrinsically aged skin. Procollagen mRNA expression in aged buttock skin is significantly lower than in young buttock skin. However, unexpectedly, photodamaged forearm skin of the elderly shows increased procollagen mRNA expression than the sun-protected, naturally aged upper-inner arm skin of the same individuals. This difference is not due to site differences, since the expression of procollagen mRNA was similar in both the forearm skin and the upper-inner arm skin of young subjects. Therefore, this increased expression of procollagen mRNA in the photoaged skin of the elderly is the result of chronic sun exposure, and may be a repair response to UV-induced collagen destruction. This repair response to UV-induced collagen destruction in human skin peaks at 40–59 years of age (21).

To compare the expressions of type I procollagen protein in aged and photoaged skin, Chung et al. (21) used two kinds of antibodies for type I procollagen. Monoclonal antihuman procollagen type I C-peptide (PIC) antibody (Takara, Shiga, Japan) usually stains intracellular procollagen within the fibroblasts, whereas monoclonal antiprocollagen type I aminoterminal extension peptide (SP1.D8) antibody (Developmental Studies Hybridoma Bank, Iowa City, IA, USA) stains the extracellular procollagen proteins as well, especially beneath the dermo-epidermal junction. The intracellular expression of procollagen protein in fibroblasts of young buttock skin is greater than that of aged buttock and upper-inner arm skin. On the other hand, fibroblasts in photoaged forearm skin express greater amounts of procollagen than the fibroblasts of sun-protected skin in the same individuals. This result indicates that fibroblasts in photoaged skin produce more procollagen protein than those in naturally aged skin. However, the extracellular expression of procollagen in photoaged skin is low, while naturally aged skin from the same individual expresses substantial amounts of procollagen at the dermo-epidermal junction. This interesting result suggests that as soon as newly synthesized procollagen is secreted from fibroblasts into the extracellular space, the procollagen is degraded by some enzymes, such as MMPs, in photodamaged skin. Thus, the procollagen available for new collagen fibril synthesis in photoaged skin decreases due to increased degradation by MMPs. It has also been reported previously that type I and type III procollagen levels are significantly lower in severely photodamaged human skin (24).

The balance between the synthesis of procollagen and the degradation of newly synthesized procollagen is important for determining the net amount of procollagen synthesis in human skin in vivo. A significant difference exists in the pathomechanisms leading to collagen deficiency in chronologically aged and photoaged skin. Naturally aged skin shows reduced collagen synthesis and an elevated MMP expression. On the other hand, during photoaging, collagen synthesis is induced by chronic UV exposure, probably as a part of the repair process, but the degradation of the collagen is outweighed by the higher levels of MMPs. Thus, the net effect of synthesis and degradation is shifted to a negative balance leading to collagen deficiency in the chronically photodamaged skin of the elderly.

Signaling pathways leading to skin aging and photoaging

Recent studies indicate that the MAP kinase signal transduction pathways play an important role in regulating a variety of cellular functions (25–27), including cell growth (28, 29), MMP expression (30) and type I procollagen synthesis (31, 32). Three distinct, but related families of MAP kinases exist: extracellular-signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) and p38 MAP kinase. Although there is ‘cross-talk’ among the pathways, the ERK pathway primarily mediates cellular responses to growth factors (28), while the JNK and p38 pathways primarily mediate cellular responses to cytokines and physical stress (28, 33, 34). It has been suggested that the dynamic balance between the growth-factor-activated ERK pathway and the stress-activated JNK and p38 pathways may be important determinants of cellular survival (28).

Downstream effectors of the MAP kinases include several transcription factors, such as Elk-1, Ets, CREB, c-Fos and c-Jun. c-Jun and c-Fos heterodimerize to form the activator protein 1 (AP-1) complex, and phosphorylation of c-Jun by JNK stimulates AP-1 transactivation activity (35–37). The binding of activated AP-1 to its response element induces the expressions of numerous genes, including certain members of the MMP family, collagenase, stromelysin and 92 kDa gelatinase (20). Also, MMPs specifically degrade connective tissue proteins such as collagen and elastin in the skin. In addition, AP-1 has also been shown to regulate type I procollagen gene expression negatively (38). This inhibition appears to result from the inhibition of procollagen transcription induction by transforming growth factor β (TGF-β) (38–40). It has also been previously demonstrated that ERK pathway activity is reduced, whereas JNK pathway activity is activated in intrinsically aged human skin in vivo, as compared with young skin (41). In this paper, it was suggested that the higher c-Jun kinase activity in intrinsically aged skin may be responsible for the increased expression of c-Jun in aged skin, which might lead to the functional activation of AP-1 (41).

As mentioned above, the level of MMP-1 protein is higher in the dermis of photoaged skin than in that of naturally aged skin (21). However, the reason for this greater expression of MMP in photoaged skin remains to be determined. We hypothesized that AP-1 activity in photoaged human skin may be higher than that of intrinsically aged skin, leading to the greater induction of connective-tissue-degrading MMPs such as collagenase and 92 kDa gelatinase in photoaged skin. We found that ERK pathway activity is more reduced, whereas stress-activated (JNK and p38) pathway activity is elevated in photoaged skin in vivo, compared with intrinsically aged skin of the same individuals (unpublished data). Furthermore, we found that AP-1 activity in photoaged skin is increased vs. intrinsically aged skin, causing a higher expression of MMPs in photoaged skin (unpublished data). Therefore, the degradation of collagen by the higher levels of MMPs in photodamaged skin results in a more severe collagen deficiency and coarser wrinkling.

Antioxidant defense mechanisms in aged skin

Several theoretical mechanisms have been proposed to explain skin aging. The free radical theory (42–44) has received particular attention. Skin is constantly exposed to reactive oxygen species (ROS) from the environment, such as air, solar radiation, ozone and air-borne pollutants, or from the normal metabolism, primarily from the mitochondrial respiratory chain wherein excess electrons are donated to molecular oxygen to generate superoxide anions. Accumulated ROS has been suggested to play an important role in the intrinsic aging and photoaging of human skin in vivo (45), and ROS has been postulated to be responsible for various cutaneous inflammatory disorders and skin cancers (46, 47).

The skin's antioxidant defense system is regulated by an interlinked network. It is becoming increasingly clear that antioxidants interact in a complex manner, so that changes in the redox status or concentration of one component may affect many other components of the system (48–50). Thus, a comprehensive and integrated antioxidant skin defense mechanism is considered to be crucial for protecting skin from ROS, and consequently for preventing the aging process. Many researchers have investigated the antioxidant defense mechanisms of human skin in vivo (51, 52) and those of mouse skin (53).

The four principal antioxidant enzymes in skin are superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR). Rhie et al. (54) reported that only catalase activity is decreased in the dermis of aged and photoaged human skin in vivo, while the levels of the other antioxidant enzymes are unchanged in the dermis. Catalase activity is lower in the dermis of photoaged skin than in that of intrinsically aged skin. Ascorbic acid levels are lower in both the epidermis and dermis of both photoaged and aged skin, while α-tocopherol is lower in the epidermis, but not in the dermis (Fig. 3). According to the free radical theory of aging, ROS increases with aging due to the reduced activity of the antioxidant defense enzymes. These results (54) were compatible with the free radical theory of aging, since decreased catalase activity in the dermis, and decreased nonenzymic antioxidant levels, such as vitamin C, in the epidermis and in the dermis of photoaged and aged human skin in vivo are believed to cause an age-associated increase in oxidative stress (ROS). Consequently, ROS, such as hydrogen peroxide, in aged skin may increase and accumulate, and this ROS would be expected to affect signaling pathways and finally lead to intrinsically aged and photoaged skin in vivo (Fig. 3) (54, 55). We found higher levels of hydrogen peroxide in skin fibroblasts derived from old people than in those of younger subjects (unpublished data). Thus, the induction and regulation of components in the endogenous antioxidant defense system may offer a good strategy for the treatment and prevention of aging and photoaging in human skin.

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Figure 3.  Antioxidant dense systems in aged and photoaged human skin in vivo. In the dermis, only catalase activity was found to significantly decrease with age, whereas SOD, GPx and GR remained unchanged. Ascorbic acid was also reduced in the dermis of aged skin. The lower antioxidant capacity of aged skin may cause an increased accumulation of ROS, thus affecting signal transduction pathways, and skin wrinkling.

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Pigmentary changes in photoaged skin

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

The immediate and delayed darkening of skin exposed to a single sunlight exposure is an acute response to UV radiation. On the other hand, freckling, mottled pigmentation, melasma and lentigo on the sun-exposed skin of the elderly are responses to chronic solar exposure. The most common pigmented lesions in sun-exposed skin include ephelides (freckling), melasma, lentigo, mottled pigmentation and pigmented seborrheic keratosis, etc. It has been reported that the patterns of pigmentary change that occur are dependent upon gender in Koreans (6). Lentigo increases with age, and is more frequent in women than men. On the other hand, seborrheic keratosis also increases with age, and this is more common in men (6).

Changes of melanocytes and pigmentation in photoaged skin

The number of dopa-positive melanocytes in human skin decreases with age by approximately 10–20% with each decade in both habitually sun-exposed and protected skin (56, 57). Despite decreased melanocyte density with aging, photoaged skin shows irregular pigmentation and, frequently, hyperpigmentation. This may be due to a higher level of dopa activity in chronically irradiated melanocytes. Heterogeneity of skin color in exposed areas of elderly skin is due to an uneven distribution of pigment cells, a local loss of melanocytes, and modified interactions between melanocytes and keratinocytes (58).

In the photoaged skin of Caucasians, the density of dopa-positive melanocytes was roughly two-fold higher than in the nonexposed skin at all ages (from 28 to 80 years), suggesting the irreversible effect of sun exposure. In the case of the melanocyte population, chronic sun exposure does not accelerate aging, but rather appears to have a net stimulatory effect on exposed melanocytes (59). This phenomenon may be an adaptive response of habitually exposed skin against the damage caused by cumulative sun exposure.

In Korean brown skin, we have also found that the number of melanocytes in sun-exposed facial skin is greater than that of sun-protected buttock skin (Fig. 4b). In Koreans, the number of melanocytes decreased with aging in sun-protected buttock skin, as in Caucasians. In Korean photoaged facial skin, DOPA activity was greater and the number of melanocytes higher with aging (Fig. 4b). The amount of melanin pigment in the sun-exposed Korean skin is greater than that in sun-protected skin on an individual basis (Fig. 4c). Melanin pigment tends to decrease slightly in sun-protected buttock skin with aging, and tends to localize mainly in the basal cell layer. On the other hand, in sun-exposed skin, the melanin pigment appears to increase with aging, and to extend to the upper spinous layers beyond the basal cell layer (Fig. 4c).

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Figure 4.  Aging- and photoaging-dependent changes of melanocytes and melanin pigments in human skin in vivo: (a) wrinkle grade, (b) dopa stain, (c) Fontana-Masson stain.

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Ephelide (Freckle)

Freckling is most frequent in individuals with red or blond hair and blue eyes, and is particularly associated with the Celtic people of Ireland (60). In the brown skin of Asians, freckling appears to be less common than in Caucasians. Freckles are characterized by hyperpigmentation of the basal cell layer without elongation of the rete ridges or an increase in the number of epidermal melanocytes. The melanocytes are larger and strongly dopa-positive. Freckles exhibit immediate pigment darkening following sun exposure and darken more readily than the surrounding normal skin.

Melasma

Melasma is an acquired irregular brown or gray-brown hypermelanosis of the face and occasionally of the neck and forearm. The etiology is attributable to sunlight, genetic predisposition and pregnancy. Different clinical forms of melasma are recognized, and facial patterns may be either centrofacial, malar or mandibular. Histologically, increased pigment may be situated epidermally, dermally or at both sites (61).

In East Asia, males and females seem to be equally affected (3), and although all races are affected, there is a particular prominence among Latinos, particularly of Caribbean origin, and among Asians.

Solar lentigo

Solar lentigo refers to circumscribed, pigmented macules on the sun-exposed skin of the elderly. The epidermal rete is elongated, and the number of melanocytes is increased (62). Usually solar lentigines are seen on older patients following chronic sun exposure. Solar lentigo is present in 90% of Caucasians older than 60 years, and its prevalence is directly correlated with increasing age (63). The face, forearm and the dorsum of the hand are common sites. The lesions are large and have an irregular edge but are usually brown. Solar lentigo is known to be more common in Caucasians and to be prevalent among those with darkly pigmented skin (64).

Mottled pigmentation

Photodamaged skin, mainly on the face and forearm, is characterized by diffuse, mottled, irregular areas of pigmentation. This is apparently paradoxical as the number of epidermal melanocytes decrease with increasing age in white skin. This generalized, irregular hyperpigmentation in aged habitually sun-exposed skin may be explained by a greater dopa-positivity in chronically irradiated melanocytes (58).

Seborrheic keratosis

Seborrheic keratoses (SKs) are common in white races, and males and females are equally affected (65, 66). It has also been reported that SKs are less common in populations with dark skin, such as the Africans and brown-skinned Asians (67, 68). These results suggest the influence of racial and ethnic differences in the prevalence of SKs. However, these lesions are a common problem in Asians. The color of these lesions can vary from a pale brown with pink tones to dark brown or black. In brown skin, most lesions seem to be brown to dark brown. Seborrheic keratosis is not a pigmentary disorder, but a benign tumor. However, because most seborrheic keratosis in Asians is usually pigmented, patients and some investigators regard them as a pigmentation problem. SKs have diverse clinical and histopathological characteristics, and are observed in 80–100% of those over 50 years (65, 69–72).

The etiology of SKs is not well understood, though they are known to show familial traits with an autosomal dominant pattern in those with a large number of lesions (73). Human papilloma virus has been suggested to be a possible cause, because of the verrucous appearance of the lesions, but no definite causal relationship has been established despite a significant amount of research (74).

Although there is still some debate, exposure to sunlight has been suggested to be a risk factor for SKs (69), and they have been reported to show a higher prevalence on exposed areas than intermittently exposed areas (66, 69). Exposure to sunlight has been suggested to play a role in the development of lesions in those predisposed to develop SKs (66, 69).

However, no well-designed study has been undertaken to investigate the clinical characteristics of SKs in Asians. Recently, Kwon et al. (66) investigated the clinical characteristics of SKs in Korean males and the relationship between SKs and sunlight exposure. SKs are believed to be less common in more pigmented skin populations (67, 68). However, such a belief may be the result of a lack of a systematized clinical study in the Asian or black-skinned populations. It has been reported that 81–100% of Caucasian males over the age of 40 with white skin have at least one SK (69, 70, 75). Similarly, the prevalence of SKs in Korean males has also been related to age; i.e., rising from 78.9% at 40 years, to 93.9% at 50 years and to 98.7% in those over 60 years (66). These results show that SKs are as common in Korean males as in the white population. Although the prevalence of SK may be similar in Asians and Caucasians, the number of SKs in Korean males appears to be less than in Caucasian males on an individual basis.

On exposed areas, body surface sites such as the face, neck and dorsum of the hands show significant increases in the prevalence of SKs by decade, while, on partly exposed areas, it was found to increase with age, but without statistical significance (66). When the estimated body surface area (BSA) is taken into account, the numbers of SKs on both the face and on the dorsum of hands were over-represented compared with the trunk. They were also concentrated on the neck and v-area. The outer forearms also showed three-fold more SKs, in terms of BSA, than neighboring the inner forearms, which are classified as partly exposed areas (66). These findings suggest that the development of SKs concentrates at exposed areas.

After controlling for many variables including age, smoking and skin types, subjects with a sun-exposure history of more than 6 h per day showed a 2.3-fold increased risk of severe SKs compared with those exposed for less than 3 h per day (66). SK lesions on sun-exposed skin were found to be usually smaller than on partly exposed skin, especially in the younger age group. Moreover, SKs on exposed skin grow significantly with aging, while those on partly exposed skin tend to remain the same size. On the other hand, the number of SKs was greater on exposed skin than on partly exposed skin. Therefore, the total area occupied by SKs was greater on exposed skin than that on partly exposed skin (66). These results suggest that sunlight causes multiple small-sized SKs, and that it also plays a role in the development and growth of SKs (66).

In summary, SKs are very common in Korean males and may be one of the major pigmentary problems. SKs are concentrated on the sun-exposed skin, especially on the face and on the dorsum of the hands. Both aging and lifetime cumulative sunlight exposure are independent contributory factors and may work synergistically.

Histological changes in photoaged skin

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

Elastic fiber alterations and solar elastosis

Elastic fibers are the insoluble structural elements of connective tissues, and have a central core of amorphous, hydrophobic cross-linked elastin surrounded by fibrillin-rich microfibrils (76). Fibrillin and elastin are mainly the products of dermal fibroblasts. Keratinocytes also express fibrillin and assemble microfibrils (77). Recently, keratinocytes were found to influence the maturation and organization of the elastin fiber network in a skin equivalent model (78). Recently Seo et al. (79) reported that keratinocytes may contribute to elastin network formation by producing tropoelastin in human skin in vivo.

The histologic findings of intrinsic aging show a general decrease in the extracellular matrix, characterized by reduced elastin and a disintegration of elastic fibers (80). Immunohistochemical staining showed significantly fewer oxytalan fibers in aged buttock skin, but elastic fibers in the upper and mid-dermis thickened and became more fragmented than those of young skin (Fig. 5a). However, in the sun-exposed photoaged skin of the elderly, few disrupted oxytalan fibers were observed in the papillary dermis (Fig. 5b). Histologic findings of photoaged skin showed most prominently features referred to as solar elastosis, which are characterized by the accumulation of dystrophic elastotic material in the reticular dermis (81–84) (Fig. 5b). Little is known about the mechanisms leading to the accumulation of elastotic material in photoaged skin, although this material stains strongly with elastic tissue stains (85, 86). This accumulation of elastotic material may be associated with increased elastin production in photodamaged skin. Ultraviolet B (UVB) irradiation has been demonstrated to upregulate tropoelastin gene expression both in vivo and in vitro (87). Moreover, increased fibrillin expression and deposition have been reported within the reticular dermis of photoaged skin (88).

image

Figure 5.  Changes of elastic fibers and solar elastosis in aged and photoaged skin. By immunohistochemical staining, oxytalan fibers were found to be significantly reduced in aged buttock skin, and the elastic fibers of the upper and mid-dermis became thicker and more fragmented than those of young skin. However, in sun-exposed forearm skin, few disrupted oxytalan fibers were found in the papillary dermis and large amounts of elastotic material were observed in the reticular dermis.

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Seo et al. (79) demonstrated that mild solar elastosis can be observed at 20 years of age in the sun-exposed facial skin of Korean subjects, and severe accumulations of elastotic materials were found in the dermis of Koreans older than 40 years of age. However, in sun-protected Korean skin, solar elastosis was not detected (79).

Effects of acute and chronic UV irradiation on elastin production

It has been reported that UVB can upregulate tropoelastin mRNA expression in cultured fibroblasts (87–89); however, other investigators have reported the opposite effect in cultured fibroblasts (90). Recently, it was reported that acute UV irradiation decreased tropoelastin mRNA expression 24 h after UV treatment in dermal fibroblasts of human skin in vivo (79). However, they demonstrated that chronic exposure of elderly photoaged skin to UV seems to upregulate tropoelastin mRNA expression in dermal fibroblasts in vivo (79). The reasons for these contrasting effects of acute and chronic UV exposure on tropoelastin expression remain to be investigated. However, it is possible that various cytokines and growth factors produced by inflammatory cells in chronically photodamaged skin may play some role in the stimulation of fibroblasts to produce more tropoelastin.

Under normal circumstances, epithelial cells, such as keratinocytes, are not considered to be elastin-producing cells. Recently, it was demonstrated that UV irradiation induces tropoelastin mRNA expression in the keratinocytes of human skin in vivo and also in cultured human keratinocytes (79). It was also shown that tropoelastin mRNA levels are increased in the forearm (sun-exposed) skin of elderly persons, as compared with the upper-inner arm (sun-protected) skin of the same individuals (79). Tropoelastin mRNA expression in photoaged skin was higher in keratinocytes and fibroblasts than in sun-protected skin (upper-inner arm) (79). Starcher et al. (91) also reported that in hairless mice, UV irradiation increased both the number and size (length and diameter) of elastic fibers in the dermis, and that modified epithelial cells surrounding the hair follicles and sebaceous glands were the source of elastin. These results suggest that keratinocytes are a source of tropoelastin after acute and chronic UV irradiation in human skin in vivo (79).

Accumulation of elastotic materials

The mechanisms for the loss of microfibrillar integrity and for the accumulation of elastotic materials in the upper dermis in photoaged skin remain to be delineated. Chronic UV exposure can induce dermatoheliosis and cause chronic inflammatory cell infiltration in photodamaged skin. Moreover, these inflammatory cells produce various proteinases, e.g., neutrophil elastase and neutrophil collagenase, which can degrade intact microfibrils rapidly (92). It is well known that MMPs, such as collagenase and gelatinase, can be induced by UV irradiation in human skin in vivo, and that this induction is enhanced in photoaged skin (14). It is therefore possible that these enzymes play important roles in disrupting the elastic fiber network in photodamaged skin.

MMP-12, human macrophage metalloelastase, is a member of the MMP family, which is the most active MMP against elastin (93). MMP-12 has also been shown to participate in the degradation of elastic fibers in emphysema (94), granulomatous skin disorders (95) and actinic damage of skin (96).

UV is known to increase MMP-12 expression in human skin in vivo, possibly in macrophages and fibroblasts (22). The UV-induced expression of MMP-12 can be inhibited by antioxidant pretreatments in human skin (22). Photoaged human skin expresses significant amounts of MMP-12 protein, which colocalizes with the solar elastosis material; moreover, the immunoreactivity of MMP-12 in exposed skin becomes stronger with age (22). The association of MMP-12 with elastotic material suggests that it may play an important role in the development of solar elastosis, the hallmark of sun-induced damage in human skin in vivo. The abnormal production of tropoelastin in both fibroblasts and keratinocytes by acute and chronic UV exposure, and its deposition and degradation by various enzymes, such as MMP-12, may contribute to the accumulation of elastotic materials in photoaged skin.

Vascular changes

A reduction of the cutaneous microvasculature has been observed in the skin of older individuals (97, 98), and potentially leads to reduced nutritional support (99). Moreover, obliterated vessels have been associated with disturbances of the normal architecture of the vascular plexus in the dermis (97). In contrast, no major disturbances of the horizontal pattern of vascular plexus have been found in intrinsically aged skin (100). Recently, we investigated the effects of photoaging vs. the intrinsic aging of human skin on cutaneous vascularization in the Korean population (101). Intrinsically aged and photoaged skins showed an age-dependent reduction in cutaneous vessel sizes. However, only photoaged skin showed a significantly reduced number of dermal vessels, particularly in subepidermal areas that displayed extensive matrix damage. This suggests that different molecular mechanisms are involved in the mediation of vascular alterations in these conditions. Acute UV irradiation results in a marked upregulation of proangiogenic and proinflammatory mediators, including vascular endothelial growth factor, and results in vascular hyperpermeability, vessel leakage, the activation of proteases and the degradation of extracellular matrix molecules. Such changes are associated with the vascular proliferation and upregulation of endothelial cell adhesion molecules with the influx of inflammatory cells into the dermis. Taken together, these changes represent an inflammatory tissue repair reaction. In addition, after chronic and repetitive damage, they result in marked degenerative changes of the upper dermis, associated with the degradation of elastic and collagen fibers and the rarification of cutaneous vessels, thus providing a less permissive environment for the maintenance of normal vessel structure and function (101). In contrast, in sun-protected skin, no major reduction in the number of vessels was detected, although the average size of cutaneous vessels was significantly reduced. This age-associated decrease in dermal vessel size may explain several of the altered physiologic characteristics of aged skin, including its pallor, reduced skin temperature and reduced UV-induced erythema (97, 98, 100). The mechanisms leading to this observed reduction in average vessel size remain unknown.

Conclusion

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

The commercial markets for cosmetics and drugs that prevent or treat photoaging are increasing very rapidly in many Asian countries. Therefore, many investigators in the dermatology and cosmetology fields have become interested in the care of Asian skins.

Many people believe that wrinkles are not a prominent feature of photoaged Asian skins, and that dyspigmentation is a major manifestation in Asian skins. However, the present study has shown that there is a statistically significant positive association between wrinkling and dyspigmentation in both Korean women and men. This suggests that Korean people with severe dyspigmentation usually tend to have severe wrinkles, and that wrinkling is a major problem in photoaged Asian skin. The wrinkle pattern and pigmentary changes of photoaged East Asian skins differ from those of Caucasians, and the relative risks of each aggravating factor may also differ. More investigation is needed on the inherent characteristics of Asian skin, and on the aging and photoaging processes in Asians.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
  10. References

This work was supported in part by the Korea Science and Engineering Foundation (KOSEF) through the Center for Aging and Apoptosis Research at Seoul National University (R11-2002-001-03001-0) and by a research agreement with the Pacific Corporation.

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  2. Abstract
  3. Clinical manifestations of photoaging in Asian skin
  4. Wrinkles in photoaged skin
  5. Causes of skin wrinkling and their relative risk in Asian skin
  6. Pigmentary changes in photoaged skin
  7. Histological changes in photoaged skin
  8. Conclusion
  9. Acknowledgments
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