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Irritability of the skin barrier: A comparison of chronologically aged and photo-aged skin in elderly and young adults
European Geriatric Medicine 2 (2011) 208–211
Research paper
Irritability of the skin barrier: A comparison of chronologically aged and photo-aged skin in elderly and young adults J. Blaak a,*, D. Lu¨ttje b, S.M. John a, N.Y. Schu¨rer a a b
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabru¨ck, Sedanstr. 115, 49090 Osnabru¨ck, Germany Klinik fu¨r Geriatrie und Palliativmedizin, Klinikum Osnabru¨ck GmbH, Osnabru¨ck, Germany
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 March 2011 Accepted 24 May 2011 Available online 28 June 2011
Purpose: The epidermal barrier resides in the stratum corneum (SC). Compared to young adults baseline barrier function of aged skin is comparable. Stress to the aged barrier results in decreased rates of repair. Barrier irritability of young vs. old, chronologically aged vs. photo-aged skin has not been examined in direct comparison. Patients and methods: Geriatric patients (mean age 81 7 SD; n = 104) underwent a dermatological examination. The irritability of young (24 3; n = 21) vs. old (82 5; n = 21), chronologically aged (ventral side of the upper arm) vs. photo-aged (dorsal aspect of the lower arm) skin was assessed, including transepidermal water loss (TEWL), SC hydration before and after 10 minutes irritation with 0.5 N NaOH under occlusion. Results: Clinical examination of aged subjects revealed a correlation between excessive dry skin and photo-aged, but not chronologically aged skin (P < 0.05). Compared to young adults’ SC hydration was lower in photo-aged skin sites of the elderly (P < 0.001). Basal TEWL was comparable in young, chronologic and photo-aged skin. Only photo-aged skin of old subjects revealed increased irritability to the alkaline irritant compared to chronologic aged and young skin (P < 0.001). Conclusion: Skin dryness and irritability in the elderly is enhanced only in photo-aged skin. ß 2011 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Skin aging Chronological aging Photo-aging Skin barrier Skin irritation Xerosis
1. Introduction Chronologic aging (genetic, intrinsic aging) is an inevitable process occurring in every organ system at a genetically determined, species- and organ-specific rate [1]. To aged skin, including: dermis, epidermis and its outermost layer the stratum corneum (SC), various structural and functional changes have been attributed. Within the dermis a decline of thickness [2], flattening of the dermal/epidermal junction [3] as well as a reduction in blood flow [4] has been studied extensively. Moreover, sebum and sweat production are decreased in aged skin [5]. The thickness of epidermis also decreases with age, which is mainly observed in sun-exposed skin [6], though SC thickness remains unchanged [7]. An increased pH [8], reduced intercellular lipid content [9] and reduced hydration [10] were observed in aged SC. Furthermore, the reduction in epidermal turnover reflects an age-dependent decrease in epidermal repair rate after minor damage, i.e. agedependent increase in skin irritability [11]. The barrier to transepidermal water loss (TEWL), which resides within the SC, is not impaired in aged compared to young adults * Corresponding author. Tel.: +49 541 4051824; fax: +49 541 4051822. E-mail addresses: [email protected] (J. Blaak), [email protected] (D. Lu¨ttje), [email protected] (S.M. John), [email protected] (N.Y. Schu¨rer).
[12]. This finding is still discussed [6]. Moreover, the aged barrier in murine and human skin is more easily perturbed by tape stripping and reveals a delayed recovery compared to young [13]. Dry, rough and scaly skin, a skin disorder called xerosis, has been attributed to decreased: sebaceous gland activity [14]; SC hydration [15]; and epidermal lipid synthesis and/or content [9,16]. Therefore, high incidence of xerosis in the elderly may not be attributed solely to sebaceous gland activity. Aged SC indeed shows a reduced water-binding capacity, which seems to be linked to a decrease in cutaneous natural moisturizing factors (NMF) [17,18]. In healthy young skin epidermal lipids, i.e. ceramides, free fatty acids and sterols are required for normal barrier function. The composition of these epidermal lipids is unchanged in aged skin, but the global lipid content decreases with age [19]. Stress to the barrier leads to increased synthesis of these lipids, which is significantly slower in aged compared to young mice [16]. Therefore, the high prevalence of dryness and itching in the elderly can be linked to decreased barrier lipid synthesis in the aged, along with reduced barrier integrity and an imbalance of barrier homeostasis [20].
1878-7649/$ – see front matter ß 2011 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. doi:10.1016/j.eurger.2011.05.011
J. Blaak et al. / European Geriatric Medicine 2 (2011) 208–211
209
Extrinsic aging results from the superposition of environmental effects on intrinsic (chronologic) aging. UV radiation is the beststudied environmental effect [21], therefore the term ‘‘photo-aging’’ is well established. Over lifetime the skin of the face, neck, hands and dorsal aspect of the lower arms are primarily exposed to UV-light, whereas the inner aspect of the upper arm and thigh as well as the buttock reflects chronologic epidermal aging. Differences in barrier function of photo-aged and chronological aged skin have been described. Reed et al. [22] revealed a delayed barrier recovery after tape stripping in photo-aged compared to chronological aged skin. However, in barrier integrity (number of tape stripping required to increase TEWL to 20 g/h/m2) no differences were observed between photo-aged and chronological aged skin. The present study was designed to evaluate barrier function, i.e. barrier irritability of chronologic versus photo-aged skin in 21 elderly compared to 21 young adults, employing a standardized irritability test, applied in occupational dermatology [23].
chosen as the standard for the descriptive statistics. Differences between groups were tested for their statistical significance employing the Mann-Whitney-U test for not normally distributed non-paired data. Wilcoxon signed-rank test was used comparing results in the course of each group. The Spearman-Rang-Correlation test was used to identify associations between parameters. The significance level was set at P < 0.05.
2. Methods
3.2. Bioengineering methods
2.1. Volunteers One hundred and four volunteers, mean age 81 7 years (25 male, 79 female) were subjected to a full body examination by a dermatologist, with focus on xerosis. None had a positive history of skin diseases. All volunteers were pigment type according to Fitzpatrick I-II to avoid pigment type dependent influences. Skin irritability was examined in 21 elderly, mean age 82 5 years (inclusion criteria: age > 70 years; 7 m, 14 f) and compared to a group of 21 young volunteers, mean age 24 3 years (inclusion criteria: age < 30 years; 10 m, 11 f). The study was approved by the University ethical committee, which gave its unanimous approval. Informed consent was obtained from all participants prior to their inclusion in the study.
SC hydration on pa and ca was measured in 21 old subjects and compared to 21 young subjects prior to irritation with 0.5 N NaOH. SC hydration was significant lower on pa of old subjects (median: 40) than young subjects (median: 55), (P < 0.001). No significant difference in SC hydration was found on ca of old patients compared to young patients (P = 0.86) (Fig. 2). Basal TEWL in young and old, ca and pa were comparable (Fig. 3). D-TEWL measurements revealed comparable results in ca and pa skin of young adults (P = 0.763), i.e. on the dorsal aspect of the lower arm and the inner aspect of the upper arm. However, DTEWL was significantly higher on pa compared to ca skin sites of old subjects (P < 0.001) as well as compared to pa skin sites of young subjects (P < 0.001) (Fig. 4).
2.2. Bioengineering methods
4. Discussion
TEWL refers to the loss of water vapor through the SC in absence of sweat gland activity. TEWL values are regarded as an indication of the skin’s barrier function [24]. Barrier perturbation by chemical and/or physical insults is accompanied by an initial increase in TEWL and is followed by a decrease in TEWL in healthy skin. TEWL was measured on the dorsal aspect of the lower arm (pa = photo-aging) and on the inner aspect of the upper arm (ca = chronologic aging), at random right or left side, using the DermaLab TEWL Module1 (Cortex Technology ApS, Halsund, Denmark). Measurements were taken after the participants had rested for 30 minutes in an environment with a temperature of 20– 22 8C and relative humidity of 48–50%, according to the guidelines given by the European Society of Contact Dermatitis [25]. Measurements were taken from clinically unchanged skin before and after application of 0.5 N NaOH 10 minutes under occlusion. Prior to the second measurement, a further drying period of 20 minutes was allowed. The difference between the two measurements was recorded as delta-TEWL (D-TEWL). D-TEWL reflects the skin’s – in particular the epidermal barrier’s – irritability through exposure to a given irritating chemical (0.5 N NaOH) over 10 minutes duration. The ‘‘electrical conductance’’, indicating SC hydration, was measured on pa and ca prior to TEWL measurements, using the DermaLab Moisture Module1 with a flat faced probe (Cortex Technology ApS, Hadsund, Denmark) according to Berardesca [26].
Xerosis is associated with sensitive skin, reported to occur in 50% of women and nearly 40% of men [27]. Xerosis, known to affect the elderly [28], is linked to changes in epidermal lipid content and composition, i.e. abnormal SC [11], reduced water binding capacity [19], seasonal influences [29] and/or pigment-type [30]. A diminution of water binding proteins has been described in chronologically aged skin (buttock) and photo-aged skin (forearm) compared to young adults: Only in photo-aged skin, an increase in free, i.e. non-protein bound water was detected [10]. Unchanged [(Fig._1)TD$IG]
2.3. Statistical analysis Data were calculated with SPSS for Windows (Version 18.0, SPSS Inc., Chicago Ill., USA). The median and 25/75 percentiles were
3. Results 3.1. Clinical findings Out of 104 elderly, 67 revealed xerosis; in 37 elderly xerosis was not diagnosed anywhere on the body. Only 15 subjects suffered of total body xerosis, in 52 cases xerosis was restricted to the face, necks, arms and legs (Fig. 1). Correlation between xerosis and photo-aging was significant (P < 0.05).
Fig. 1. Of 104 elderly n = 67 had xerosis, thereof n = 52 xerosis was found in photoaged skin (face, neck, arms, legs). Correlation between xerosis and photo-aging was significant (P < 0.05). In 37 patients xerosis was not detected, of those only n = 15 showed signs of photo-aging.
[(Fig._2)TD$IG]
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[(Fig._4)TD$IG]
J. Blaak et al. / European Geriatric Medicine 2 (2011) 208–211
Fig. 2. Data represent median and 25/75 percentiles of SC hydration in 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologically aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. SC hydration was significantly (P < 0.001) lower on pa of old subjects (median: 40) than young subjects (median: 55). AU: arbitrary unit. SC: stratum corneum.
Fig. 4. Data represent median and 25/75 percentiles of D-transepidermal water loss (TEWL) of 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologic aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. D-transepidermal water loss (TEWL) was significantly higher on pa in old subjects compared to ca (P < 0.001) and pa (P < 0.001) in young subjects.
filaggrin content was observed in the aged facial skin [31,32]. The authors discuss a correlation between this finding and the observed lack of xerosis on facial skin. In contrast to facial skin, low profilaggrin biosynthesis has been attributed to xerosis of the lower leg [15]. The present dermatologic examination of elderly revealed xerosis in 64% of cases (Fig. 1). However, most of the elderly revealed xerosis on their skin exposed to the environment. These findings are in accordance with the literature [33,34]. Impairment in protein hydration may reason the observed high incidence of xerosis in photo-aged skin. Further studies on the relevance of profilaggrin biosynthesis for xerosis in relation to topography are required. Moreover, xerotic skin is more irritable than normal skin [35] and barrier function of the aged epidermis is less resistant to external stressors than in young epidermis [13,16]. The correlation of the incidence of dry and photo-aged skin (P < 0.05) lead to the question of increased irritability in photo-aged compared to chronologically aged skin.
Basal TEWL rates were comparable in all skin sites tested. These findings are in accordance with the literature [13]. Prior studies observed even slightly reduced basal TEWL rates in the aged [36], possibly based on decreased sweating, microcirculation, moisture content and temperature, as well as increased corneocyte size or a combination thereof [6,11,12]. A standardized irritability test, applied in occupational dermatology [23], has been conducted in elderly patients compared to sex-matched young controls. The integrity of the SC is diminished in photo-aged skin of older patients: upon a brief 10 minutes NaOH-irritation, D-TEWL values were significantly higher compared to chronologically aged skin of old and/or young adults (P < 0.001). These findings need further delineation according to the irritant used. An amount of 0.5 N NaOH is a strong base; therefore an increased pH in photo-aged skin may reason the irritability. The elevation of the skin surface pH leads to an impaired barrier function in the skin of elderly, shown as reduced barrier homeostasis and barrier integrity/cohesion [8]. On one hand a reduced alkaline neutralization capacity [37] and on the other hand an increased skin surface pH have been documented for aged skin [8,38,39]. The reduction of the buffering capacity leads to an enhanced sensitivity to external irritants [37]. The question whether the increased irritability to NaOH in photoaged skin correlates with an increased pH compared to chronological aged skin needs to be further delineated. The significantly higher D-TEWL in photo-aged skin of the elderly compared to that of the young might be explained by a diminution in secreted lamellar body derived contents, and a failure of these contents to form a continuous series of multilamellar bilayers within the intercellular SC spaces in the photoaged skin of the elderly [13]. Further, in the murine model a 30 to 35% decrease in the content of all main lipid classes and a decreased basal lipid synthesis has been demonstrated [16]. Stress to the photo-aged skin of the elderly may initiate a changed (slower) signal cascade to initiate repair than in young or chronologically aged skin. Further studies are required to enlighten the biochemical pathomechanisms of photo- compared to chronologically aged skin in the elderly. With respect to the high prevalence of xerosis in aged, particularly photo-aged skin, a specific skin care treatment for elderly seems to be necessary. Topical treatment of dry skin includes application of physiologic lipids (ceramides, cholesterol,
[(Fig._3)TD$IG]
Fig. 3. Data represent median and 25/75 percentiles of basal transepidermal water loss (TEWL) of 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologically aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. Basal TEWL in young and old subjects, ca and pa, was comparable.
J. Blaak et al. / European Geriatric Medicine 2 (2011) 208–211
fatty acids), hydrating agents (urea, glycerol) or active agents (allantoin, a-bisabolol) [40]. We further point out that, because of the reduced buffer capacity and increased skin surface pH in elderly pigment type I-II, maintenance of the physiological acidic skin pH may be essential. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Wurm S, Wiest M, Tesch-Ro¨mer C. Theorien zu Alter(n) und Gesundheit. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 2010;53:498– 503. [2] Waller JM, Maibach HI. Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol 2005;11(4):221–35. [3] Neerken S, Lucassen GW, Bisschop MA, Lenderink E, Nuijs TAM. Characterization of age-related effects in human skin: a comparative study that applies confocal laser scanning microscopy and optical coherence tomography. J Biomed Opt 2004;9:274–81. [4] Kelly RI, Pearse R, Bull R, Leveque JL, de Rigal J, Mortimer P. The effects of aging on cutaneous microvasculature. J Am Acad Dermatol 1995;33:749–56. [5] Pochi PE, Strauss JS, Downing DT. Age-related changes in sebaceous gland activity. J Invest Dermatol 1979;73(1):108–11. [6] Farage MA, Miller KW, Elsner P, Maibach HI. Structural characteristics of the aging skin: a review. Cutan Ocul Toxicol 2007;26:343–57. [7] Lavker RM. Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 1979;73(1):59–66. [8] Choi EH, Man MQ, Xu P, Xin S, Liu Z, Crumrine DA, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 2007;127(12):2847–56. [9] Saint-Leger D, Francois AM, Leveque JL, Stousemayer TJ, Grove GL, Kligman AM. Age-associated changes in stratum corneum lipids and their relation to dryness. Dermatologica 1988;177:159–64. [10] Gniadecka M, Nielsen OF, Wessel S, Heidenheim M, Christensen DH, Wulf HC. Water and protein structure in photoaged and chronically aged skin. J Invest Dermatol 1998;111(6):1129–33. [11] Elias PM, Ghadially R. The aged epidermal permeability barrier: basis for functional abnormalities. Clin Geriatr Med 2002;18(1):103–20. [12] Wilhelm KP, Brandt M, Maibach HI. Transepidermal water loss and barrier function of aging human skin. In: Fluhr JW, Elsner P, Berardesca E, Maibach HI, editors. Biongineering of the skin: water and the stratum corneum. Boca Raton: CRC-Press; 2005. p. 143-158. [13] Ghadially R, Brown BE, Sequeira-Martin SM, Feingold KR, Elias PM. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995;95(5):2281–90. [14] Zouboulis CC, Boschnakow A. Chronological ageing and photoageing of the human sebaceous gland. Clin Exp Dermatol 2001;26(7):600–7. [15] Horii I, Nakayama Y, Obata M, Tagami H. Stratum corneum hydration and amino acid content in xerotic skin. Br J Dermatol 1989;121(5):587–92. [16] Ghadially R, Brown BE, Hanley K, Reed JT, Feingold KR, Elias PM. Decreased epidermal lipid synthesis accounts for altered barrier function in aged mice. J Invest Dermatol 1996;106(5):1064–9.
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[17] Rawlings AV, Harding CR. Moisturization and skin barrier function. Dermatol Ther 2004;17(Suppl. 1):43–8. [18] Takahashi M, Tezuka T. The content of free amino acids in the stratum corneum is increased in senile xerosis. Arch Dermatol Res 2004;295(10): 448–52. [19] Rogers J, Harding C, Mayo A, Banks J, Rawlings A. Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 1996;288(12):765–70. [20] Barco D, Gimenez-Arnau A. Xerosis: a dysfunction of the epidermal barrier. Actas Dermosifiliogr 2008;99(9):671–82. [21] Krutmann J. Pathomechanisms of photoaged skin. In: Farage MA, Miller KW, Maibach HI, editors. Textbook of Aging Skin. Berlin Heidelberg: Springer Verlag; 2010. p. 101–7. [22] Reed JT, Elias PM, Ghadially R. Integrity and permeability barrier function of photoaged human epidermis. Arch Dermatol 1997;133(3):395–6. [23] John SM, Uter W. Meteorological influence on NaOH-irritation varies with body site. Arch Dermatol Res 2005;296(7):320–6. [24] Machado M, Salgado TM, Hadgraft J, Lane ME. The relationship between transepidermal water loss and skin permeability. Int J Pharm 2010;384:73–7. [25] Pinnagoda J, Tupker RA, Agner T, Serup J. Guidlines for transepidermal water loss (TEWL) measurement. Contact Dermatitis 1990;22:164. [26] Berardesca E. EEMCO guidance for the assessment of stratum corneum hydration: electrical methods. Skin Res Technol 1997;3:126–32. [27] Willis CM, Shaw S, De Lacharriere O, Baverel M, Reiche L, Jourdain R, et al. Sensitive skin: an epidemiological study. Br J Dermatol 2001;145:258–63. [28] Norman RA. Xerosis and pruritus in the elderly: recognition and management. Dermatol Ther 2003;16(3):254–9. [29] Simon M, Bernard D, Minondo AM, Camus C, Fiat F, Corcuff P, et al. Persistence of both peripheral and non-peripheral corneodesmosomes in the upper stratum corneum of winter xerosis skin versus only peripheral in normal skin. J Invest Dermatol 2001;116:23–30. [30] Gunathilake R, Schurer NY, Shoo BA, Celli A, Hachem JP, Crumrine D, et al. pHregulated mechanisms account for pigment-type differences in epidermal barrier function. J Invest Dermatol 2009;129(7):1719–29. [31] Bhawan J, Andersen W, Lee J, Labadie R, Solares G. Photoaging versus intrinsic aging: a morphologic assessment of facial skin. J Cutan Pathol 1995;22(2):154–9. [32] Tezuka T, Qing J, Saheki M, Kusuda S, Takahashi M. Terminal differentiation of facial epidermis of the aged: immunohistochemical studies. Dermatology 1994;188:21–4. [33] Smith DR, Sheu HM, Hsieh FS, Lee YL, Chang SJ, Guo YL. Prevalence of skin disease among nursing home patients in southern Taiwan. Int J Dermatol 2002;41:754–9. [34] Smith DR, Atkinson R, Tang S, Yamagata Z. A survey of skin disease among patients in an Australien Nursing Home. J Epidemiol 2002;12:336–40. [35] Choi EH, Kim MJ, Ahn SK, Park WS, Son ED, Nam GW, et al. The skin barrier state of aged hairless mice in a dry environment. Br J Dermatol 2002;147(2):244–9. [36] Wilhelm KP, Cua AB, Maibach HI. Skin aging. Effect on transepidermal water loss, stratum corneum hydration, skin surface pH, and casual sebum content. Arch Dermatol 1991;127(12):1806–9. [37] Raab W. Skin cleansing in health and disease. Wien Med Wschr 1990;108:4– 10. [38] Thune P, Nilsen T, Hanstad IK, Gustavsen T, Lovig Dahl H. The water barrier function of the skin in relation to the water content of stratum corneum, pH and skin lipids. The effect of alkaline soap and syndet on dry skin in elderly, non-atopic patients. Acta Derm Venereol 1988;68(4):277–83. [39] Man MQ, Xin SJ, Song SP, Cho SY, Zhang XJ, Tu CX, et al. Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population. Skin Pharmacol Physiol 2009;22(4):190–9. [40] Proksch E, Lachapelle JM. The management of dry skin with topical emollients - recent perspectives. J Dtsch Dermatol Ges 2005;3:768–74.
Research paper
Irritability of the skin barrier: A comparison of chronologically aged and photo-aged skin in elderly and young adults J. Blaak a,*, D. Lu¨ttje b, S.M. John a, N.Y. Schu¨rer a a b
Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabru¨ck, Sedanstr. 115, 49090 Osnabru¨ck, Germany Klinik fu¨r Geriatrie und Palliativmedizin, Klinikum Osnabru¨ck GmbH, Osnabru¨ck, Germany
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 March 2011 Accepted 24 May 2011 Available online 28 June 2011
Purpose: The epidermal barrier resides in the stratum corneum (SC). Compared to young adults baseline barrier function of aged skin is comparable. Stress to the aged barrier results in decreased rates of repair. Barrier irritability of young vs. old, chronologically aged vs. photo-aged skin has not been examined in direct comparison. Patients and methods: Geriatric patients (mean age 81 7 SD; n = 104) underwent a dermatological examination. The irritability of young (24 3; n = 21) vs. old (82 5; n = 21), chronologically aged (ventral side of the upper arm) vs. photo-aged (dorsal aspect of the lower arm) skin was assessed, including transepidermal water loss (TEWL), SC hydration before and after 10 minutes irritation with 0.5 N NaOH under occlusion. Results: Clinical examination of aged subjects revealed a correlation between excessive dry skin and photo-aged, but not chronologically aged skin (P < 0.05). Compared to young adults’ SC hydration was lower in photo-aged skin sites of the elderly (P < 0.001). Basal TEWL was comparable in young, chronologic and photo-aged skin. Only photo-aged skin of old subjects revealed increased irritability to the alkaline irritant compared to chronologic aged and young skin (P < 0.001). Conclusion: Skin dryness and irritability in the elderly is enhanced only in photo-aged skin. ß 2011 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Skin aging Chronological aging Photo-aging Skin barrier Skin irritation Xerosis
1. Introduction Chronologic aging (genetic, intrinsic aging) is an inevitable process occurring in every organ system at a genetically determined, species- and organ-specific rate [1]. To aged skin, including: dermis, epidermis and its outermost layer the stratum corneum (SC), various structural and functional changes have been attributed. Within the dermis a decline of thickness [2], flattening of the dermal/epidermal junction [3] as well as a reduction in blood flow [4] has been studied extensively. Moreover, sebum and sweat production are decreased in aged skin [5]. The thickness of epidermis also decreases with age, which is mainly observed in sun-exposed skin [6], though SC thickness remains unchanged [7]. An increased pH [8], reduced intercellular lipid content [9] and reduced hydration [10] were observed in aged SC. Furthermore, the reduction in epidermal turnover reflects an age-dependent decrease in epidermal repair rate after minor damage, i.e. agedependent increase in skin irritability [11]. The barrier to transepidermal water loss (TEWL), which resides within the SC, is not impaired in aged compared to young adults * Corresponding author. Tel.: +49 541 4051824; fax: +49 541 4051822. E-mail addresses: [email protected] (J. Blaak), [email protected] (D. Lu¨ttje), [email protected] (S.M. John), [email protected] (N.Y. Schu¨rer).
[12]. This finding is still discussed [6]. Moreover, the aged barrier in murine and human skin is more easily perturbed by tape stripping and reveals a delayed recovery compared to young [13]. Dry, rough and scaly skin, a skin disorder called xerosis, has been attributed to decreased: sebaceous gland activity [14]; SC hydration [15]; and epidermal lipid synthesis and/or content [9,16]. Therefore, high incidence of xerosis in the elderly may not be attributed solely to sebaceous gland activity. Aged SC indeed shows a reduced water-binding capacity, which seems to be linked to a decrease in cutaneous natural moisturizing factors (NMF) [17,18]. In healthy young skin epidermal lipids, i.e. ceramides, free fatty acids and sterols are required for normal barrier function. The composition of these epidermal lipids is unchanged in aged skin, but the global lipid content decreases with age [19]. Stress to the barrier leads to increased synthesis of these lipids, which is significantly slower in aged compared to young mice [16]. Therefore, the high prevalence of dryness and itching in the elderly can be linked to decreased barrier lipid synthesis in the aged, along with reduced barrier integrity and an imbalance of barrier homeostasis [20].
1878-7649/$ – see front matter ß 2011 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. doi:10.1016/j.eurger.2011.05.011
J. Blaak et al. / European Geriatric Medicine 2 (2011) 208–211
209
Extrinsic aging results from the superposition of environmental effects on intrinsic (chronologic) aging. UV radiation is the beststudied environmental effect [21], therefore the term ‘‘photo-aging’’ is well established. Over lifetime the skin of the face, neck, hands and dorsal aspect of the lower arms are primarily exposed to UV-light, whereas the inner aspect of the upper arm and thigh as well as the buttock reflects chronologic epidermal aging. Differences in barrier function of photo-aged and chronological aged skin have been described. Reed et al. [22] revealed a delayed barrier recovery after tape stripping in photo-aged compared to chronological aged skin. However, in barrier integrity (number of tape stripping required to increase TEWL to 20 g/h/m2) no differences were observed between photo-aged and chronological aged skin. The present study was designed to evaluate barrier function, i.e. barrier irritability of chronologic versus photo-aged skin in 21 elderly compared to 21 young adults, employing a standardized irritability test, applied in occupational dermatology [23].
chosen as the standard for the descriptive statistics. Differences between groups were tested for their statistical significance employing the Mann-Whitney-U test for not normally distributed non-paired data. Wilcoxon signed-rank test was used comparing results in the course of each group. The Spearman-Rang-Correlation test was used to identify associations between parameters. The significance level was set at P < 0.05.
2. Methods
3.2. Bioengineering methods
2.1. Volunteers One hundred and four volunteers, mean age 81 7 years (25 male, 79 female) were subjected to a full body examination by a dermatologist, with focus on xerosis. None had a positive history of skin diseases. All volunteers were pigment type according to Fitzpatrick I-II to avoid pigment type dependent influences. Skin irritability was examined in 21 elderly, mean age 82 5 years (inclusion criteria: age > 70 years; 7 m, 14 f) and compared to a group of 21 young volunteers, mean age 24 3 years (inclusion criteria: age < 30 years; 10 m, 11 f). The study was approved by the University ethical committee, which gave its unanimous approval. Informed consent was obtained from all participants prior to their inclusion in the study.
SC hydration on pa and ca was measured in 21 old subjects and compared to 21 young subjects prior to irritation with 0.5 N NaOH. SC hydration was significant lower on pa of old subjects (median: 40) than young subjects (median: 55), (P < 0.001). No significant difference in SC hydration was found on ca of old patients compared to young patients (P = 0.86) (Fig. 2). Basal TEWL in young and old, ca and pa were comparable (Fig. 3). D-TEWL measurements revealed comparable results in ca and pa skin of young adults (P = 0.763), i.e. on the dorsal aspect of the lower arm and the inner aspect of the upper arm. However, DTEWL was significantly higher on pa compared to ca skin sites of old subjects (P < 0.001) as well as compared to pa skin sites of young subjects (P < 0.001) (Fig. 4).
2.2. Bioengineering methods
4. Discussion
TEWL refers to the loss of water vapor through the SC in absence of sweat gland activity. TEWL values are regarded as an indication of the skin’s barrier function [24]. Barrier perturbation by chemical and/or physical insults is accompanied by an initial increase in TEWL and is followed by a decrease in TEWL in healthy skin. TEWL was measured on the dorsal aspect of the lower arm (pa = photo-aging) and on the inner aspect of the upper arm (ca = chronologic aging), at random right or left side, using the DermaLab TEWL Module1 (Cortex Technology ApS, Halsund, Denmark). Measurements were taken after the participants had rested for 30 minutes in an environment with a temperature of 20– 22 8C and relative humidity of 48–50%, according to the guidelines given by the European Society of Contact Dermatitis [25]. Measurements were taken from clinically unchanged skin before and after application of 0.5 N NaOH 10 minutes under occlusion. Prior to the second measurement, a further drying period of 20 minutes was allowed. The difference between the two measurements was recorded as delta-TEWL (D-TEWL). D-TEWL reflects the skin’s – in particular the epidermal barrier’s – irritability through exposure to a given irritating chemical (0.5 N NaOH) over 10 minutes duration. The ‘‘electrical conductance’’, indicating SC hydration, was measured on pa and ca prior to TEWL measurements, using the DermaLab Moisture Module1 with a flat faced probe (Cortex Technology ApS, Hadsund, Denmark) according to Berardesca [26].
Xerosis is associated with sensitive skin, reported to occur in 50% of women and nearly 40% of men [27]. Xerosis, known to affect the elderly [28], is linked to changes in epidermal lipid content and composition, i.e. abnormal SC [11], reduced water binding capacity [19], seasonal influences [29] and/or pigment-type [30]. A diminution of water binding proteins has been described in chronologically aged skin (buttock) and photo-aged skin (forearm) compared to young adults: Only in photo-aged skin, an increase in free, i.e. non-protein bound water was detected [10]. Unchanged [(Fig._1)TD$IG]
2.3. Statistical analysis Data were calculated with SPSS for Windows (Version 18.0, SPSS Inc., Chicago Ill., USA). The median and 25/75 percentiles were
3. Results 3.1. Clinical findings Out of 104 elderly, 67 revealed xerosis; in 37 elderly xerosis was not diagnosed anywhere on the body. Only 15 subjects suffered of total body xerosis, in 52 cases xerosis was restricted to the face, necks, arms and legs (Fig. 1). Correlation between xerosis and photo-aging was significant (P < 0.05).
Fig. 1. Of 104 elderly n = 67 had xerosis, thereof n = 52 xerosis was found in photoaged skin (face, neck, arms, legs). Correlation between xerosis and photo-aging was significant (P < 0.05). In 37 patients xerosis was not detected, of those only n = 15 showed signs of photo-aging.
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Fig. 2. Data represent median and 25/75 percentiles of SC hydration in 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologically aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. SC hydration was significantly (P < 0.001) lower on pa of old subjects (median: 40) than young subjects (median: 55). AU: arbitrary unit. SC: stratum corneum.
Fig. 4. Data represent median and 25/75 percentiles of D-transepidermal water loss (TEWL) of 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologic aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. D-transepidermal water loss (TEWL) was significantly higher on pa in old subjects compared to ca (P < 0.001) and pa (P < 0.001) in young subjects.
filaggrin content was observed in the aged facial skin [31,32]. The authors discuss a correlation between this finding and the observed lack of xerosis on facial skin. In contrast to facial skin, low profilaggrin biosynthesis has been attributed to xerosis of the lower leg [15]. The present dermatologic examination of elderly revealed xerosis in 64% of cases (Fig. 1). However, most of the elderly revealed xerosis on their skin exposed to the environment. These findings are in accordance with the literature [33,34]. Impairment in protein hydration may reason the observed high incidence of xerosis in photo-aged skin. Further studies on the relevance of profilaggrin biosynthesis for xerosis in relation to topography are required. Moreover, xerotic skin is more irritable than normal skin [35] and barrier function of the aged epidermis is less resistant to external stressors than in young epidermis [13,16]. The correlation of the incidence of dry and photo-aged skin (P < 0.05) lead to the question of increased irritability in photo-aged compared to chronologically aged skin.
Basal TEWL rates were comparable in all skin sites tested. These findings are in accordance with the literature [13]. Prior studies observed even slightly reduced basal TEWL rates in the aged [36], possibly based on decreased sweating, microcirculation, moisture content and temperature, as well as increased corneocyte size or a combination thereof [6,11,12]. A standardized irritability test, applied in occupational dermatology [23], has been conducted in elderly patients compared to sex-matched young controls. The integrity of the SC is diminished in photo-aged skin of older patients: upon a brief 10 minutes NaOH-irritation, D-TEWL values were significantly higher compared to chronologically aged skin of old and/or young adults (P < 0.001). These findings need further delineation according to the irritant used. An amount of 0.5 N NaOH is a strong base; therefore an increased pH in photo-aged skin may reason the irritability. The elevation of the skin surface pH leads to an impaired barrier function in the skin of elderly, shown as reduced barrier homeostasis and barrier integrity/cohesion [8]. On one hand a reduced alkaline neutralization capacity [37] and on the other hand an increased skin surface pH have been documented for aged skin [8,38,39]. The reduction of the buffering capacity leads to an enhanced sensitivity to external irritants [37]. The question whether the increased irritability to NaOH in photoaged skin correlates with an increased pH compared to chronological aged skin needs to be further delineated. The significantly higher D-TEWL in photo-aged skin of the elderly compared to that of the young might be explained by a diminution in secreted lamellar body derived contents, and a failure of these contents to form a continuous series of multilamellar bilayers within the intercellular SC spaces in the photoaged skin of the elderly [13]. Further, in the murine model a 30 to 35% decrease in the content of all main lipid classes and a decreased basal lipid synthesis has been demonstrated [16]. Stress to the photo-aged skin of the elderly may initiate a changed (slower) signal cascade to initiate repair than in young or chronologically aged skin. Further studies are required to enlighten the biochemical pathomechanisms of photo- compared to chronologically aged skin in the elderly. With respect to the high prevalence of xerosis in aged, particularly photo-aged skin, a specific skin care treatment for elderly seems to be necessary. Topical treatment of dry skin includes application of physiologic lipids (ceramides, cholesterol,
[(Fig._3)TD$IG]
Fig. 3. Data represent median and 25/75 percentiles of basal transepidermal water loss (TEWL) of 21 young subjects (YS) and 21 old subjects (OS) in photo-aged (pa) and chronologically aged (ca) skin. Skin surface area equivalent to pa was the dorsal aspect of the lower arm and to ca the inner aspect of the upper arm. Basal TEWL in young and old subjects, ca and pa, was comparable.
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fatty acids), hydrating agents (urea, glycerol) or active agents (allantoin, a-bisabolol) [40]. We further point out that, because of the reduced buffer capacity and increased skin surface pH in elderly pigment type I-II, maintenance of the physiological acidic skin pH may be essential. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Wurm S, Wiest M, Tesch-Ro¨mer C. Theorien zu Alter(n) und Gesundheit. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 2010;53:498– 503. [2] Waller JM, Maibach HI. Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol 2005;11(4):221–35. [3] Neerken S, Lucassen GW, Bisschop MA, Lenderink E, Nuijs TAM. Characterization of age-related effects in human skin: a comparative study that applies confocal laser scanning microscopy and optical coherence tomography. J Biomed Opt 2004;9:274–81. [4] Kelly RI, Pearse R, Bull R, Leveque JL, de Rigal J, Mortimer P. The effects of aging on cutaneous microvasculature. J Am Acad Dermatol 1995;33:749–56. [5] Pochi PE, Strauss JS, Downing DT. Age-related changes in sebaceous gland activity. J Invest Dermatol 1979;73(1):108–11. [6] Farage MA, Miller KW, Elsner P, Maibach HI. Structural characteristics of the aging skin: a review. Cutan Ocul Toxicol 2007;26:343–57. [7] Lavker RM. Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 1979;73(1):59–66. [8] Choi EH, Man MQ, Xu P, Xin S, Liu Z, Crumrine DA, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol 2007;127(12):2847–56. [9] Saint-Leger D, Francois AM, Leveque JL, Stousemayer TJ, Grove GL, Kligman AM. Age-associated changes in stratum corneum lipids and their relation to dryness. Dermatologica 1988;177:159–64. [10] Gniadecka M, Nielsen OF, Wessel S, Heidenheim M, Christensen DH, Wulf HC. Water and protein structure in photoaged and chronically aged skin. J Invest Dermatol 1998;111(6):1129–33. [11] Elias PM, Ghadially R. The aged epidermal permeability barrier: basis for functional abnormalities. Clin Geriatr Med 2002;18(1):103–20. [12] Wilhelm KP, Brandt M, Maibach HI. Transepidermal water loss and barrier function of aging human skin. In: Fluhr JW, Elsner P, Berardesca E, Maibach HI, editors. Biongineering of the skin: water and the stratum corneum. Boca Raton: CRC-Press; 2005. p. 143-158. [13] Ghadially R, Brown BE, Sequeira-Martin SM, Feingold KR, Elias PM. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 1995;95(5):2281–90. [14] Zouboulis CC, Boschnakow A. Chronological ageing and photoageing of the human sebaceous gland. Clin Exp Dermatol 2001;26(7):600–7. [15] Horii I, Nakayama Y, Obata M, Tagami H. Stratum corneum hydration and amino acid content in xerotic skin. Br J Dermatol 1989;121(5):587–92. [16] Ghadially R, Brown BE, Hanley K, Reed JT, Feingold KR, Elias PM. Decreased epidermal lipid synthesis accounts for altered barrier function in aged mice. J Invest Dermatol 1996;106(5):1064–9.
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