Ebook Textbook of aging skin: Part 2

(BQ) Part 2 book Textbook of aging skin presents the following contents: Biomarkers, in vitro techniques, pigmentation, diseases associated with aging, malignant skin conditions, on malignant skin conditions, bioengineering methods and tools, percutaneous penetration,...

46 Tobacco Smoke and Skin Aging* Akimichi Morita Introduction As early as 1971, Daniell [1] found that tobacco smoking has a deleterious effect on the skin, and smoker’s wrinkles are the typical clinical features of smokers A recent epidemiological study has clearly shown that tobacco smoking is one of the numerous factors contributing to premature skin aging, which is dependent on age, sex, pigmentation, sun exposure history, alcohol consumption, and other factors [2À5] In a further cross section study, sun exposure, pack years of smoking history, and potential confounding variables were assessed by questionnaire Facial wrinkles were quantified using the Daniell score Logistic statistical analysis of the data revealed that age, pack year, and sun exposure independently contributed to facial wrinkle formation [6] In this survey, age (OR = 7.5, 95% CI = 1.87À30.16), pack year (OR = 5.8, 95% CI = 1.72À19.87), and sun exposure (OR = 2.65, 95% CI = 1.0À7.0) independently contributed to the formation of facial wrinkles, as estimated by a logistic regression analysis model Using silicone rubber replicas combined with computerized image processing, an objective measurement of skin’s topography, the association between wrinkle formation and tobacco smoking was investigated Sixty-three volunteers were enrolled by assessing their skin replicas, in an attempt to elucidate the association between tobacco smoking and wrinkles [7] The replica analysis showed that the depth (Rz) and variance (Rv) of furrows (Rv) in subjects with smoking history !35 pack years were significantly higher than nonsmokers (P < 0.05) The lines of furrows (Rl) in subjects with smoking history were significantly lower than in nonsmokers (P < 0.05) [7, 8] Tobacco smoking, which is regarded as an important environmental factor, can potentially cause ‘‘tobacco wrinkles’’ [1], although chronic exposure of skin to ultraviolet (UV) radiation results in marked alterations in the structure and composition of the epidermis and dermis, i.e., photoaging [9À11] In a recent study, tobacco smoking per se or smoking combined with UV exposure were strong predictors of skin aging [12] Molecular Mechanisms of TobaccoInduced Skin Aging Tobacco smoking probably exerts its deleterious effects on skin directly through its irritant components on the epidermis and indirectly on the dermis via the blood circulation [3, 13] The decreased stratum corneum moisture of the face contributes to facial wrinkling because of the direct toxicity of the smoke Pursing the lips during smoking with contraction of facial muscles and squinting because of the irritating of smoke may cause the formation of wrinkling around the mouth and in the crow’s foot area [14] The changes in the dermis of macromolecular metabolism have been brought into focus as a major factor leading to skin aging [15] Specifically, it has been demonstrated that accumulation of elastosis material is accompanied by the degradation of matrix protein, which is mediated by matrix metalloproteinases (MMPs) in skin aging The molecular alteration in the dermis includes the decrease of collagen synthesis, induction of MMPs, abnormal accumulation of elastic fibers, and proteoglycans [16À18] Effects of Tobacco Smoke on Skin Models In Vitro The biosynthesis of new collagen was decreased significantly by tobacco smoke extracts in cultured skin fibroblasts [18] The studies also showed that the production of both procollagen types I and III, the precursors of collagen, were significantly decreased from the supernatant of cultured fibroblast treated with tobacco smoke extracts, using Western blot analysis [18] This result ∗ Originally published as Tobacco Smoke and Skin Aging in Halliwell, B.B., Poulsen, H.E (eds.), Cigarette Smoke and Oxidative Stress, Heidelberg, Springer, 2006 pp 379–385 Reprinted with permission M A Farage, K W Miller, H I Maibach (eds.), Textbook of Aging Skin, DOI 10.1007/978-3-540-89656-2_46, # Springer-Verlag Berlin Heidelberg 2010 448 46 Tobacco Smoke and Skin Aging indicated that the final production of collagen secreted into the medium is reduced, regardless of the rate of collagen synthesis in the cell tested in 3H-proline incorporation Although elastic fibers account for only 2–4% of extracellular matrix, these provide elasticity and resilience to normal skin Tobacco smoke extracts induced the significant increase in tropoelastin mRNA in cultured skin fibroblasts Accumulation of abnormal elastic material (termed solar elastosis) is the prominent histopathologic alterations in photoaged skin [19, 20] Boyd et al [21] reported that tobacco smoking could facilitate smoke’s elastosis of the subjects with an average of 42 pack years of tobacco smoking In an in vitro study using cultured skin fibroblasts, tobacco smoke extracts induced elevation of tropoelastin This might be attributed to premature skin aging The expressions of MMP-1 and MMP-3 mRNA, extracellular matrix (ECM)-associated members of the MMPs gene family, were induced in cultured skin fibroblast stimulated with tobacco smoke extracts in a dose-dependent manner [18] These results support the concept that MMPs are primary mediators of connective tissue damage in skin exposed to tobacco smoke extracts and of the premature skin aging In addition, expression of TIMP-1 and TIMP-3 remained unchanged [18] By inducing the expressions of MMP-1 and MMP-3, but not the induction of tissue inhibitor of MMPs, tobacco smoke extracts could alter their ratio in favor of the induction of MMPs and appears to result in a more degradative environment that produces loss of cutaneous collagen [18] In addition, MMPs comprise a family of degradative enzymes, which are responsible for the degradation of extracellular matrix components such as native collagen, elastin fibers, and various proteoglycans MMP-3 and MMP-7 may play a key role in the degradation of elastin and proteoglycans [22] MMP-7 was increased in fibroblasts induced by tobacco smoke extract Effect of Tobacco Smoke In Vivo In a clinical study, significant higher levels of MMP-1 mRNA were observed in the buttock skin of smokers, compared with nonsmokers, using quantitative real-time PCR [23] The elevated enzyme should lead to the degradation of collagen, elastic fibers, and proteoglycans Therefore, the observations in dermal connective tissue induced by the treatments of tobacco suggested an imbalance between the biosynthesis and degradation, with less repair capacity on the face of the ongoing degradation, which leads to the loss of collagen and elastic fibers, manifesting clinically as aging appearance of skin Although staining of skin specimen and biochemical analysis of photodamaged skin demonstrated increased glycosaminoglycan content of sun-damaged skin, the underlying molecular pathogenesis remains unclear Versican, the large chondroitin sulfate (CS) proteoglycan, has been identified in the dermis in association with elastic fibers, which contain a hyaluronic acid-binding domain The core protein has been postulated to play a role in molecular interactions and specifically, to facilitate the binding of these macromolecules to other matrix components or cytokines such as transforming growth factor (TGF) [24] Decorin, a small CS proteoglycan, has been shown to codistribute with collagen fibers and postulated to function in cell recognition, possible by connecting extracellular matrix components and cell surface glycoproteins [25] Targeted disruption of decorin synthesis in mice resulted in a significant reduction in the tensile strength of skin [26] There was a decrease in the proportion of large CS proteoglycan (versican) and a concomitant increase in the proportion of small dermatan sulfate proteoglycan (decorin) as a function of age as reported by Carrino et al [27] Ito et al [28] also observed that versican was stained strongly in young rats and faintly in old rats On the other hand, decorin was faintly stained in the young rats and distinctly stained in the old rats There were several reports concerning the changes of proteoglycans on photoaging, especially UVB irradiation [29, 30] The analysis of new synthesized proteoglycans showed a marked increase after UVB radiation in mice [30] Versican and decorin immunostaining increased in photoaged tissue samples, accompanied by similar alterations in gene expression [29] Tobacco smoke extracts decreased both versican protein and mRNA levels in cultured akin fibroblasts However, tobacco smoke extract exposure resulted in a significant increase of decorin These results are similar to those observed in photoaging Based on experimental evidence, a working model for UVA damage skin was proposed, in which UV irradiation gene expression was mediated via the generation of singlet oxygen through a pathway involving activation of transcription factor AP-2 [10] In order to define whether the reactive oxygen species (ROS) were involved in upregulation of MMPs induced by tobacco, sodium azide (NaN3), l-ascorbic acid, and vitamin E, which are potent quenchers of singlet oxygen and other ROS, were employed NaN3, l-ascorbic acid, and vitamin E abrogated the induction of MMPs after exposure of fibroblast to tobacco smoke extract Among the antioxidant reagents, l-ascorbic acid most obviously diminished the increase in Tobacco Smoke and Skin Aging MMP-1 expression level on exposure of fibroblasts to tobacco smoke extracts [18] This points to the fact that ROS were most probably responsible for the enhanced induction of MMPs by tobacco smoke extract The TGF-b1 is a multifunctional cytokine that regulates cell proliferation and differentiation, tissue remodeling, and repair [31] TGF-b1 is a potent growth inhibitor in the epidermis, playing an important role in the maintenance of tissue homeostasis In the dermis, however, TGF-b1 acts as a positive growth factor, inducing the synthesis of extracellular matrix proteins TGF-b signals through a heteromeric complex of type I/II TGF-b receptors initiate signal transduction [32, 33] A recent report showed that UV irradiation can cause downregulation of TGF-b type II receptor mRNA and protein, and induction of Smad7 mRNA and protein in human skin [34] Tobacco smoke extracts induced the latent form TGF-b, not the active form, assayed by enzyme-linked immunosorbent assay (ELISA), in the supernatants of cultured skin fibroblasts [35] The induction of endogenous TGF-b1 from tobacco-exposed cells contributes to the intracellular defense capacity Fibroblasts responses to TGF-b1 are mediated through its active form binding to the cell surface receptor Tobacco smoke extracts blocked cellular responsiveness to TGF-b1 through the induction of nonfunctional latent form and downregulation of TGF-b1 receptor [35] Exogenous addition of TGF-b1 might be useful to stimulate the collagen production or to protect against the deleterious effects of tobacco smoke Conclusion Tobacco smoke contains numerous compounds, with at least 3,800 constituents [36] Just which constituents contributed to the damage of connective tissue is still unclear The tobacco-induced skin aging provides a tool for studying the effects of smoking Also, detailed knowledge may provide a motivation to stop smoking, especially among those who are more concerned about their appearances than the potential internal damage associated with smoking References Daniell HW Smoker’s wrinkles: A study in the epidemiology of ‘‘crow’s feet Ann Intern Med 1971;75:873–880 Ernster VL, Grady D, Miike R, et al Facial wrinkling in men and women, by smoking status Am J Public Health 1995;85:78–82 Frances C Smoker’s wrinkles: epidemiological and pathogenic considerations Clin Dermatol 1998;16:565–570 46 Grady D, Ernster V Does cigarette smoking make you ugly and old? Am J Epidemiol 1992;135:839–842 Kadunce DP, Burr R, Gress R, et al Cigarette smoking: risk factor for premature facial wrinkling Ann Intern Med 1991;114:840–844 Yin L, Morita A, Tsuji T Skin aging induced by ultraviolet exposure and tobacco smoking: evidence from epidemiological and molecular studies Photodermatol Photoimmunol Photomed 2001;17: 178–183 Yin L, Morita A, Tsuji T Skin premature aging induced by tobacco smoking: The objective evidence of skin replica analysis J Dermatol Sci 2001b;27(Suppl 1):S26–S31 Yin L, Morita A, Tsuji T Tobacco smoking: a role of premature skin aging Nagoya Med J 2000;43:165–171 Fisher GJ, Talwar HS, Lin J, et al Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-transretinoic acid Photochem Photobiol 1999;69:154–157 10 Grether-Beck S, Buettner R, Krutmann J Ultraviolet A radiationinduced expression of human genes: Molecular and photobiological mechanisms Biol Chem 1997;378:1231–1236 11 Wenk J, Brenneisen P, Meewes C, et al UV-induced oxidative stress and photoaging Curr Probl Dermatol 2001;29:83–94 12 Leung W-C, Harvey I Is skin ageing in the elderly caused by sun exposure or smoking? Br J Dermatol 2002;147:1187–1191 13 Lofroth G Environmental tobacco smoke: overview of chemical composition and genotoxic components Mutat Res 1989;222:73–80 14 Smith JB, Fenske NA Cutaneous manifestations and consequences of smoking J Am Acad Dermatol 1996;34:717–732 15 Uitto J, Fazio MJ, Olsen DR Molecular mechanisms of cutaneous aging: Age-associated connective tissue alterations in the dermis J Am Acad Dermatol 1989;21:614–622 16 Fisher GJ, Voorhees JJ Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo J Investig Dermatol Symp Proc 1998;3:61–68 17 Shuster S Smoking and wrinkling of the skin Lancet 2001;358:330 18 Yin L, Morita A, Tsuji T Alterations of extracelluar matrix induced by tobacco smoke extract Arch Dermatol Res 2006;292: 188–194 19 Montagna W, Kirchner S, Carlisle K Histology of sun-damaged human skin J Am Acad Dermatol 1989;21:907–918 20 Tsuji T Ultrastucture of deep wrinkles in the elderly J Cutan Pathol 1987;14:158–164 21 Boyd AS, Stasko T, King LE Jr., et al Cigarette smoking-associated elastotic changes in the skin J Am Acad Dermatol 1999;41:23–26 22 Saarialho-Kere U, Kerkela E, Jeskanen L, et al Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage J Invest Dermatol 1999;113:664–672 23 Lahmann C, Bergemann J, Harrison G, et al Matrix metalloprotease-1 and skin ageing in smokers Lancet 2001;357:935–936 24 Fisher LW, Termine JD, Young MF Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species J Biol Chem 1989;264:4571–4576 25 Zimmermann DR, Ruoslahti E Multiple domains of the large fibroblast proteoglycan, versican EMBO J 1989;8:2975–2981 26 Danielson KG, Baribault H, Homes DF, et al Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility J Cell Biol 1997;136:729–743 27 Carrino DA, Sorrell JM, Caplan AI Age-related changes in the proteoglycans of human skin Arch Biochem Biophys 2000;373:91–101 449 450 46 Tobacco Smoke and Skin Aging 28 Ito Y, Takeuchi J, Yamamoto K, et al Age differences in immunohistochemical localizations of large proteoglycan, PG-M/versican, and small proteoglycan, decorin, in the dermis of rats Exp Anim 2001;50:159–166 29 Bernstein EF, Fisher LW, Li K, et al Differential expression of the versican and decorin genes in photoaged and sun-protected skin: Comparison by immunohistochemical and northern analyses Lab Invest 1995;72:662–669 30 Margelin D, Fourtanier A, Thevenin T, et al Alterations of proteoglycans in ultraviolet-irradiated skin Photochem Photobiol 1993; 58:211–218 31 Massague J TGF-beta signal transduction Annu Rev Biochem 1998;67:753–791 32 Kadin ME, Cavaille-Coll MW, Gertz R, et al Loss of receptors for transforming growth factor beta in human T-cell malignancies Proc Natl Acad Sci USA 1994;91:6002–6006 33 Piek E, Heldin CH, Ten Dijke P Specificity, diversity, and regulation in TGF-beta superfamily signaling FASEB J 1999;13: 2105–2124 34 Quan T, He T, Voorhees JJ, et al Ultraviolet irradiation blocks cellular responses to transforming growth factor-beta by down-regulating its type-II receptor and inducing Smad J Biol Chem 2001;276: 26349–26356 35 Yin L, Morita A, Tsuji T Tobacco smoke extract induces age-related changes due to the modulation of TGF-b Exp Dermatol 2003;12: 51–56 36 Bartsch H, Malaveille C, Friesen M, et al Black (air-cured) and blond (flue-cured) tobacco cancer risk IV: molecular dosimetry studies implicate aromatic amines as bladder carcinogens Eur J Cancer 1993;29A:1199–1207 25 Unique Skin Immunology of the Lower Female Genital Tract with Age Paul R Summers Introduction It has been long recognized that the genital tract must be able to defend against significant microbial exposures In this area of medicine, old theories that may have even acquired some attributes of folklore must be revised to include new knowledge Through the last century, popular ideas regarding mechanisms of microbial defenses in the genital tract have reflected the medical thinking of each era In the time of antisepsis of the early twentieth century, lactic acid from the lactobacillus was proposed as the chief regulatory vaginal antiseptic Subsequently, the possibility of antiseptic action from hydrogen peroxide-producing lactobacilli was considered, although little hydrogen peroxide would be expected to be produced in the naturally anaerobic environment of the vaginal lumen With the influence of the more recent antibiotic era, research interest has focused upon bacteriocins, unique but relatively weak lactobacillus-derived antibiotics Theories of microbial defense have evolved further in the current, more enlightened era of immunology Rapid advances in the area of immunology have now disclosed complex immune defenses in the genital epithelium that have a significant antimicrobial impact, moderated by estrogen From the immune standpoint, the lower genital tract has the following competing roles: (1) to facilitate the various aspects of reproduction and (2) to simultaneously prevent the access of locally resident microbes to the upper genital tract and to the peritoneal cavity To facilitate a primary function in reproduction, the immune responsiveness of the lower female genital tract is blunted Ovulation, fertilization, pregnancy, labor, and delivery of the infant are all mediated by immune mechanisms that may not be optimal for microbial defense A blunted humoral immune response may be compensated by an active innate or cellmediated response For example, sperm may be highly immunogenic If sperm are detected by the humoral immune system, the development of antisperm antibodies can reduce fertility [1] It is important for the vaginal immune system to identify potential pathogens, but not to target sperm or the fetus, or to disrupt the immune mechanisms of fertility Microbial and immune events in the female urethra mirror the status of the vaginal vestibule [2] The immune function and microbial flora of the vaginal vestibule and urethra change in a parallel fashion in response to the effects of aging and hormone cycles Hormone changes alter the morphology and mucosal defenses Menopausal decline in innate immune defenses in the vaginal mucosa allows colonization with potential uropathogens and increases the risk for bladder infection Humoral Immunity The humoral immune system associated with vaginal mucosa is unique Mucosal surfaces outside the genital tract develop in conjunction with lymphoid tissue that predominantly produces IgA At other body sites, IgA may have a significant role in mucosal defense against microbes With the absence of associated lymphoid tissue, vaginal mucosa releases only limited quantities of any category of immunoglobulin at all stages of life IgG is present in vaginal secretions The relatively small amount of IgG is serum-derived as well as locally produced in the vaginal and cervical mucosa [3] With the relative absence of a local source of IgA, more IgG than IgA is detected in vaginal secretions [4] The converse is true for mucosal surfaces elsewhere in the body Cervical secretions have a higher concentration of IgA than vaginal secretions [5] This finding is consistent with the presumed protective role of cervical mucus to prevent ascent of microbes into the endometrial cavity The concentration of IgA in vaginal secretions declines by 90% after hysterectomy so the upper genital tract may be assumed to be the primary source of the small quantity of IgA that is present in the vaginal lumen [6] It is reasonable to assume a similar decline in lower genital tract immunoglobulins after the menopause, with the minimal production of cervical mucus and vaginal secretions at that time in life Cervical secretion of IgG and IgA into the vaginal pool M A Farage, K W Miller, H I Maibach (eds.), Textbook of Aging Skin, DOI 10.1007/978-3-540-89656-2_25, # Springer-Verlag Berlin Heidelberg 2010 254 25 Unique Skin Immunology of the Lower Female Genital Tract with Age varies during the menstrual cycle with the highest levels prior to ovulation during the proliferative phase, but with an 80% decline at the time of ovulation [7] The limited amount of immunoglobulin in vaginal secretions may lower the risk for the development of antisperm antibodies It is reasonable to speculate that sperm survival may be enhanced in some fashion by the further decline in immunoglobulins around the time of ovulation Disruption of vaginal immunoglobulin homeostasis can be harmful Electrical loop excision of the cervical transformation zone (LEEP) may allow an unregulated humoral immune response at that site Serum antisperm antibodies have been identified in women who are sexually active while the cervical LEEP site is healing [8] Innate Immunity The innate immune system has major importance in preventing invasion of potentially pathogenic microbes normally found in the lower genital tract and on the perirectal skin During the reproductive years, an active innate immune response compensates somewhat for the blunted humoral and cell-mediated immune response in the lower female genital tract (> Table 25.1) Sexually transmitted diseases develop when sexually acquired pathogens have the ability to evade these standing defenses [9] Human beta defensins (HBD) 1, 2, and 5, secretory leukocyte protease inhibitor (SLPI), elafin, and mannose binding lectin (MBL) have been demonstrated in vaginal secretions [9] The highest concentration of SLPI is in the cervical mucus plug, although it is expressed in secretions throughout the female genital tract SLPI blocks the action of various destructive enzymes that may be released by pathogens Elafin is an important protein that inhibits inflammation-related tissue damage by blocking elastase, which may be released by activated neutrophils Elafin also has antimicrobial activity Leukocytes and vaginal epithelial cells are the main sources of Table 25.1 Important characteristics of the cervical transformation zone during the reproductive years High concentration of elements of cell-mediated immunity to interact with viruses and to prevent ascent of bacteria into the upper genital tract and peritoneum Macrophages are involved in cervical ripening prior to labor Macrophages and granulocytes are involved in cervical dilation during labor defensins [10] Defensins are antibiotic substances that are active against various bacteria and yeast Surfactant proteins in vaginal mucosal secretions (SP-A, SP-D) protect against viral infections, including HIV-1 and herpes simplex virus (HSV) [11] Human neutrophil peptides (HNP 1–3) also suppress HSV in vaginal secretions [12] These secretory products of the innate immune system are considered to be estrogen dependent, since many are the result of local mucosal metabolism, and the secretory fluid that contains these substances requires estrogen stimulation Menopause results in a decline in the mucosaldependent elements of the innate immune system Minor congenital defects in the innate immune system, such as polymorphisms which result in deficiency of mannose binding lectin (MBL), increase the risk of symptomatic infection [13] MBL provides a target for complement activation by binding to the cell surface of pathogenic microbes MBL is produced mainly in the liver and most likely arrives in the vaginal secretions as a transudate from the blood stream MBL is a significant factor in vaginal mucosal defense against pathogens, although the MBL level in vaginal secretions is much lower than the level normally found in the systemic circulation It is not clear whether MBL is produced by vaginal mucosal cells During the reproductive years, toll-like receptors (TLRs) 1, 2, 3, 5, and are expressed in vaginal mucosal cells TLR 1, 2, and mainly target bacteria TLR is directed against virus, and TLR controls fungi [9] The expression of TLRs is estrogen-dependent This may explain the pre-pubertal and possibly post menopausal increased mucosal susceptibility to pathogens such as streptococcus or Neisseria gonorrhea Cell-Mediated Immunity Langerhans cells are abundant in vaginal and cervical mucosa [14] In the lower female genital tract, T cells and Langerhans cells are most prevalent in the normal cervical transformation zone, so the cervical transformation zone is assumed to be the major site for cell-mediated immune reactions in this area of the human body [15] The likely immune consequences of excision of this important area by extensive LEEP or cervical cone biopsy have not been determined (> Table 25.1) If the human skin is considered to be a major immune organ, then the cervix should be considered to have special immune function in that organ Chronic cervicitis, often detected on cervical biopsy in asymptomatic women is actually a misnomer, as the normal cervical transformation zone is a site of significant immune activity in normal health Pathogenic Unique Skin Immunology of the Lower Female Genital Tract with Age microbes can activate cervical inflammation, but the presence of numerous immune cells is actually physiologic The increased vulnerability of the relatively fragile transitional epithelium in the transformation zone may require better standing defenses to prevent ascending infection During the reproductive years, and to a greater extent during pregnancy, estrogen down-regulates antigen presenting cells This results in a shift toward a Th2 immune response [16, 17] Although this has not been studied with specific reference to the female lower genital tract, a Th2 response down-regulates the defensins and other secretory products of the innate immune system [18] This relative immune compromise is presumed to be important for normal fertility and pregnancy However, there are consequences, such as an increased risk for allergic contact dermatitis, as well as increased susceptibility to yeast, viruses, and other pathogens Sexually transmitted diseases typically have mechanisms to avoid cell-mediated immunity [19] The abundant macrophages and granulocytes in the cervical transformation zone are regulated by hormone changes of pregnancy Reflecting the immune suppression of pregnancy, the number of macrophages in the cervical transformation zone declines in early pregnancy, and then increases in preparation for labor Macrophages are involved in cervical ripening just prior to the onset of labor, and macrophages and granulocytes have a significant role in cervical dilation [20] Immune Changes with Age Innate immune defenses of the vaginal mucosa are compromised with aging Estrogen influences the expression of TLRs in vaginal mucosa [21, 22] (> Tables 25.2 and > 25.3) This loss of TLR expression increases the risk for colonization with pathogens The post menopausal lack of epithelial cell maturation results in loss of vaginal surface barrier function Pathogens can invade the more readily traumatized fragile epithelium Estrogen deficiency leads to a decline in mucosal secretions that contain the antimicrobial constituents of the innate immune system The neutral vaginal pH after the menopause reflects loss of the acid defense as well as a significant decline in vaginal mucosal metabolic ability Cell-mediated immunity is estrogen and age dependent Langerhans cells are most prevalent in vulvar skin during the reproductive years [23] Estrogen receptors on dendritic cells moderate the maturation of functional dendritic cells from precursor cells [24] There is a decline in Langerhans cell function with aging, as well as a decreased Langerhans cell count by approximately 50% [25, 26] 25 Table 25.2 Characteristics of the lower female genital tract under the influence of estrogen Innate immunity TLR 1, 2, 3, 5, HBD 1, 2, 3, SLPI MBL SP-A SP-D etc Humoral immunity Very low IgA very low IgG IgG > IgA Cell-mediated immunity Depressed Th1 tendency for enhanced Th2 TLR toll like receptor; HBD human beta defensin; SLPI secretory leukocyte protease inhibitor; MBL mannose binding lectin; SP surfactant proteins Table 25.3 Characteristics of the lower female genital tract in the absence of estrogen Innate immunity Decreased expression of TLRs decrease in all secretory products Humoral immunity Further decline in IgA with decreased cervical secretions Cell-mediated immunity Decline in langerhans cell count decline in cytokine responsiveness estrogenassociated suppression of Th1 response is eliminated TLR toll like receptor; HBD human beta defensin; SLPI secretory leukocyte protease inhibitor; MBL mannose binding lectin; SP surfactant proteins A decreased response to cytokines is also characteristic of aging [18] The immunologically active cervical transformation zone is gradually eliminated by the aging process of squamous metaplasia Antigen presenting cells are still present in the vaginal mucosa after menopause [27] Post menopausal estrogen replacement can reactivate deficient vaginal mucosal cellmediated immune function Asthma is a good example of the estrogen effect upon cell-mediated immunity Asthma is influenced by the estrogen-related shift of cell-mediated immunity from a Th1 to a Th2 environment Asthma is more prevalent in males than females prior to puberty, but higher in females with the rise in estrogen after puberty [28] Asthma may become less severe after menopause following the decline in Th1 suppression [29] Hormone replacement therapy after menopause may make asthma worse [30] Similarly, post menopausal estrogen replacement may restore a Th2 environment that favors vaginal colonization with yeast 255 256 25 Unique Skin Immunology of the Lower Female Genital Tract with Age Conclusion Lower female genital tract immune defenses are complex and are not yet completely understood Clearly, the immune system plays a major role in regulating vaginal microflora, but unfortunately, many pathogens have mechanisms to evade the immune defenses Estrogen promotes the innate system, but suppresses the cell-mediated response in the lower genital tract Humoral immunity appears to play only a small role in this portion of the female body Immune function during the reproductive years reflects a balance between the need to protect against infection and the requirements of reproduction 14 15 16 17 18 References Hjort H Do antisperm antibodies reduce fecundity? A mini review in historical perspective Am J Reprod Immunol 1998;40:215–222 Kunin CM, Evans C, Bartholomew D, Bates G The antimicrobial defense mechanism of the female urethra: a reassessment J Urol 2002;168:413–419 Brandtzaeg P Mucosal immunity in the female genital tract J Reprod Immunol 1997;36(1):23–50 Quesnel A, Cu-Uvin S, Murphy D, Ashley RL, Flanigan T, Neutra MR Comparative analysis of methods for collection and measurement of immunoglobulins in cervical and vaginal secretions of women J Immunol Methods 1997;202:153–161 Crowley-Nowick PA, Bell MC, Brockwell R, Edwards RP, Chen S, Partridge EE, Mestecky J Rectal immunization for induction of specific antibody in the genital tract of women J Clin Immunol 1997;17:370–379 Jalanti R, Isliker H Immunoglobulin in human cervicovaginal secretions Int Arch Allergy Appl Immunol 1977;53:402–408 Nardelli-Haefliger D, Wirthner D, Schiller JT, Lowy DR, Hildesheim A, Ponci F, De Grandi P Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles J Natl Cancer Inst 2003;95(15):1128–1137 Nicholson SC, Robindson TN, Sargent IC, Hallan NF Fertil and Steril 1996;65(4):871–873 Horne AW, Stock SJ, King AE Innate immunity and disorders of the female reproductive tract Reproduction 2008;135:739–749 10 Klotman ME, Chang TL Defensins in innate antiviral immunity Nat Rev Immunol 2006;6:447–456 11 Meschi J, Crouch EC, Skolnik P, Yahya K, Holmskov U, Leth-Larsen R, Tornoe I, Tecle T, White MR, Hartshorn KL Surfactant protein D bibds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication J Gen Virol 2005;86:3097–3107 12 John M, Keller MJ, Fam EH, Cheshenko K, Kasowitz A Cervicovaginal secretions contribute to innate resistance to herpes simplex virus infection J Infect Dis 2005;192:1731–1740 13 Babula O, Lazdane G, Kroica J, Ledger WJ, Witkin SS Relation between recurrent vulvovaginal candidiasis, vaginal concentrations 19 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Lee SK, Chang EJ Trichomonas vaginalis inhibits proinflammatory cytokine production in macrophages by suppressing NF-kappaB activation Mol Cells 2004;18: 177–185 Sakamoto Y, Moran P, Bulmor JN, Searle RF, Robson SC Macrophages and not granulocytes are involved in cervical ripening J Reprod Immunol 2005;66:161–173 Pioli PA, Amiel E, Schaefer TM, Connolly JE, Wira CR, Guyre PM Differential expression of toll-like receptors and in tissues of the human female reproductive tract Infect Immun 2004;72: 5799–5806 Sonnex C Influence of ovarian hormones on urogenital infection Sex Transm Infect 1998;74:11–19 Harper WF, McNicol EM A histological study of normal vulval skin from infancy to old age Br J Dermatol 1977;96:249–253 Paharkova-Vatchkova V, Maldonado R, Kovats S Estrogen preferentially promotes the differentiation of CD11c+ CD11bintermediate dendritic cells from bone marrow precursors J Immunol 2004; 172:1426–1436 Nomura I, Goleva E, Howell MD, et al Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes J Immunol 2003;171:3262–3269 Gilchrest B, Murphy G, Soter N Effect of chronological aging and ultraviolet irradiation on Langerhans cells in human epidermis J Invest Dermatol 1982;79:85–88 Fahey JV, Prabhala RH, Guyre PM, Wira CR Antigen-presenting cells in the human female reproductive tract: analysis of antigen presentation in pre-and post-menopausal women Am J Reprod Immunol 1999;42:49–57 Yawn BP, Wollan P Kurland MJ, Scanlon P A longitudinal study of asthma prevalence in a community population of school age children J Pediatr 2002;140(5):576–581 Balzano G, Fuschillo S, Melillo G, Bonini S Asthma and sex hormones Allergy 2001;56(1):13–20 Kos-Kudla B, Ostrowska Z, Marek B, et al Effects of hormone replacement therapy on endocrine and spirometric parameters in asthmatic postmenopausal women Gynecol Endocrinol 2001;15(4): 304–311 Specialized Skin: Genital Subject Index A Ablative lasers, 606, 817, 818, 1020, 1022, 1147, 1156–1158 Absorbent products, 859, 1123, 1124 Acetyl hexapeptide‐3 (Argireline1), 1094, 1101, 1112 Acetyl octapeptide‐3, 1094, 1101, 1112 Acetyl tetrapeptide‐5 (Eyeseryl1), 1094, 1111 Acetyl tetrapeptide‐9 (AcTP1), 1094, 1097, 1100 Acetyl tetrapeptide‐11 (AcTP2), 1094, 1097, 1100 Acid mantle, 30, 65, 139, 664, 665, 814 Acne, 358, 396, 406, 496, 518, 738, 762, 764, 765, 803, 817, 873, 876, 878, 931, 932, 935–937, 940, 951, 952, 954, 1144, 1153–1156, 1158–1160, 1190, 1200 ACSSSPSKHCG peptide, 1089 Actinic aging, 13, 14, 781–784 Actinic field carcinogenesis, 49 Actinic keratosis (AK), 40, 41, 329, 330, 547–549, 556, 567–571, 574–576, 581, 604, 607, 765 Acute phase of inflammation, 643 Adipose-derived stem cell (ADSC), 201–211, 782–783 ADSC-CM, 203–205, 209, 783 Adult, 14, 25, 45, 97, 113, 123, 131, 148, 159, 187, 192, 201, 241, 284, 301, 334, 343, 356, 364, 378, 417, 479, 487, 504, 527, 545, 567, 579, 589, 609, 623, 639, 653, 668, 677, 695, 715, 737, 757–766, 771, 799, 826, 839, 845, 857, 871, 884, 902, 914, 921, 936, 950, 960, 973, 999, 1027, 1048, 1056, 1079, 1143, 1175, 1187, 1197 Adult incontinence, 857, 859 Adult phase, 16, 612, 641 Advanced ADSC Protein Extract (AAPE), 208 Advanced glycation endproducts (AGEs), 289, 303, 307, 308, 464 Adverse social factors, 444–445 Age, 5–11, 13–17, 20, 21, 25, 28–30, 32, 33, 37, 38, 40, 41, 45–48, 50, 51, 57–60, 63–67, 69–72, 88, 93 – bias, 975–976 – differences, 169, 442–445, 777, 778, 847, 849 – spots, 38, 496, 516, 519, 583, 758, 984, 1063, 1064, 1190 Aged skin, 8, 9, 19, 27–34, 37–40, 65, 90, 93–98, 112–117, 130–132, 143, 144, 168, 179, 215, 231, 282–286, 289, 301, 306 Aging, 5–11, 13–17, 19, 25–34, 37–42, 45–52, 55–72, 85–90, 93–98, 101–103, 105, 106, 109–118, 121–127, 129–137, 143, 144, 147–156, 162–168, 170 – concerns, 1189 – skin, 5–11, 13–17, 19, 20, 25–34, 37–42, 45–52, 55, 59–72, 77–90, 93–98, 101–106, 109–118, 121–127, 129–137, 139–144, 147–156, 159–170, 173–181, 183–188 – vulvar skin, 1128–1129 Agreement, 19–21, 142, 152, 270, 283, 346, 371, 706, 732, 733, 736, 757, 806, 921–927, 963, 976, 1190, 1200 Agrin, 116–117 a6 integrin, 193, 194, 196, 574 Airborne allergens, 643–645 Alcohol consumption, 444, 445, 783, 877, 939 Allergic contact dermatitis, 213, 533, 534, 602, 825, 829, 830, 846, 935, 1003, 1048 Allergic reactions, 533, 644, 715, 937, 1031, 1064, 1168 Alopecia, 8, 11, 96, 102, 302, 350, 357, 951, 1145 Alpha hydroxy acids (AHA), 235–237, 531, 934, 937, 938, 954, 1022, 1063, 1065–1067, 1075, 1153, 1154 Amino acid, 29, 30, 64, 65, 77–79, 87, 109, 113, 115, 126, 136, 141–143, 147, 278, 298, 304, 318, 333, 371, 385, 413, 429, 464, 479, 509, 514, 570, 620, 621, 653–655, 659, 687, 706, 707, 709, 711, 721, 736, 801, 814, 850, 931, 991, 1065, 1073, 1074, 1111 Anaerobes, 257, 880, 883, 885 Anaerobic energy pathways, 297–298, 303 Anatomical location, 377–380, 382, 681, 689, 1014 Anatomical sites, 401, 402, 580, 681, 697, 706, 707, 711, 772, 800, 802, 833, 837, 841, 851, 983, 984, 1003, 1014, 1027–1031, 1043, 1045, 1127 Anatomical variations, 173, 174, 265, 984–985, 987–988 Anatomic studies, 697–698 Anatomy, 52, 179, 243, 549, 666, 700, 914, 1000, 1021, 1148, 1178 Androgen, 97, 135, 136, 143, 281, 343, 350, 355, 358, 678, 932, 1002, 1014 Anesthesia, 393, 623, 790, 1154, 1158, 1160–1162, 1164, 1165, 1170 Angiogenesis, 17, 79–81, 105, 115–117, 122, 213, 286, 603, 626, 897–904, 1092 Animal models, 5–11, 85, 94, 97, 195, 209, 214, 365, 396, 477, 478, 484, 505, 575–576, 592, 607, 620, 623, 627, 781–785, 792, 806, 807, 939 Anisotropy, 729 Anorexia nervosa (AN), 966 Antagonistic pleiotropy, 590 Anti-aging, 216, 217, 236, 237, 308, 807, 929, 939, 940, 973, 1055–1059, 1069–1077, 1197–1205 Anti-aging skin care, 929, 939, 940, 1197–1205 Antiaging treatment, 271–272, 1189 Anti-inflammatory, 136, 215, 227, 234, 406, 496, 534, 591, 603, 620, 792, 793, 816–818, 932, 936, 1058, 1059, 1075, 1082, 1090 Antimelanogenic, 201, 203–205, 209 Anti-microbial immune defense, 644 Anti-oxidant, 47, 94, 201, 203–205, 231, 236, 288, 289, 304–307, 314, 317, 318, 324, 327, 329, 330, 413, 414, 416–418, 422–424, 436, 437, 439, 448, 477, 479–483, 498, 538, 573, 591, 709, 804, 811, 815–817, 939, 940, 992, 1058, 1059, 1070, 1072, 1074, 1075, 1090, 1109–1111, 1154, 1199 Anxiety, 639, 646, 647, 668, 937, 949, 950, 952, 954, 959–963, 967 Apoptosis, 47, 51, 94, 96, 97, 148, 152, 153, 183, 188, 197, 205, 286, 288, 289, 295, 301, 303, 305, 307, 313, 314, 327, 328, 413, 415, 417, 423, 430, 453, 463, 466, 487, 545, 546, 559, 570, 572–577, 582, 583, 588, 591–594, 603, 606, 613, 708, 801, 802, 904, 938, 1021, 1056, 1079, 1110, 1111 Appendages, 135–136, 163, 175, 179, 277, 366, 382, 441, 609, 718, 722, 739, 771, 898, 1079, 1152 Appendegeal route, 771 Aquaporin, 655, 930, 1097 Aquaporin‐3 (AQP‐3), 26, 655, 931, 932 Arginine deiminase, 817 Artefill1, 1152 A-scan ultrasound, 681 Ascorbic acid, 94, 234, 236, 448, 498, 992, 1022, 1072, 1081, 1082, 1110 Asian skin, 504, 984, 1019–1024 Asteatotic eczema, 531 1208 Subject Index Asthma, 255, 630, 640–642, 830, 954 Atopic dermatitis (AD), 232, 279, 378, 382, 395, 418, 530, 591, 639–649, 654, 659, 707, 709, 711, 723, 763, 764, 803, 805, 811, 815, 834, 876, 877, 879, 952 Adenosintriphosphate (ATP), 101, 103, 279, 296–301, 303–307, 313–316, 318, 422, 455, 506, 514, 623, 624 Atrophic vaginitis, 987, 1128, 1130–1131, 1134 Atypical nevi, 558, 569, 581 Autoimmune disorders, 131, 534–536 Avidin–biotin complex (ABC) technique, 133, 149–151 B Baby Boomers, 1175, 1197 Bacteria, 241, 247, 254, 257, 394, 427, 428, 509, 642, 644, 649, 664, 789, 800, 802, 803, 806, 807, 811, 812, 814, 815, 817, 818, 871–879, 883, 884, 887, 890, 932, 933, 936, 1047, 1081, 1199 Bacterial infections, 131, 259, 538, 648, 667, 826, 878, 879, 884, 1132, 1134 Bamacan, 117 Barrier, 25, 37, 55, 85, 106, 121, 130, 139, 163, 173, 210, 213, 230, 247, 255, 277, 343, 357, 361, 371, 377, 393, 401, 411, 429, 456, 506, 527, 583, 588, 619, 642, 653, 663, 677, 687, 695, 705, 715, 725, 735, 758, 771, 801, 814, 825, 833, 845, 857, 871, 885, 897, 932, 987, 1002, 1019, 1027, 1047, 1065, 1070, 1089, 1123, 1194, 1199 Barrier function, 26, 37, 55, 130, 140, 163, 173, 210, 213, 230, 250, 255, 279, 357, 361, 371, 377, 393, 401, 418, 429, 583, 588, 642, 653, 687, 695, 705, 715, 725, 735, 758, 807, 814, 829, 834, 849, 879, 932, 1002, 1019, 1027, 1047, 1071, 1131, 1194 Basal cell carcinoma (BCC), 532, 546, 549, 554–556, 558, 562, 567, 568, 570, 571, 573, 575–577, 588, 602–607, 954 Basal trans-epidermal water loss (TEWL), 284 Base excision repair (BER), 102, 288, 325, 329, 546 Basement membrane, 25, 28, 49, 77–90, 109, 116, 117, 121–127, 136, 163, 226, 280–282, 333, 334, 453, 466, 496, 534–536, 559, 574, 579, 590, 592, 898 Basement membrane proteoglycans, 116, 117 Basic fibroblast growth factor (bFGF), 105, 203, 385, 386, 516, 904, 1082 Baumann skin type indicator (BSTI), 929, 930, 938, 940 Baumann skin typing system (BSTS), 929–940 Beauty, 234, 235, 237, 289, 509, 749, 799, 949–950, 1140, 1178, 1187, 1191, 1193, 1194, 1197–1205 Behaviors, 41, 46, 59, 112, 115, 123, 162, 170, 194, 195, 197, 265, 477, 549, 573, 613, 689, 725, 736, 740, 741, 744, 745, 815, 883, 951, 952, 959, 967, 994, 1058, 1122–1124, 1187, 1190, 1203 Behind the knee (BTK), 838–842 Benign mucous membrane pemphigoid, 534, 535 Benign neoplasm, 38, 396 Benzoic acid, 31, 32, 130, 179, 696–698, 776, 778, 834, 849, 937 Benzoyl peroxide (BPO), 406, 932, 936 Bereavement, 529, 967 Bifidobacterium, 799, 803, 805, 806, 817, 818, 884 Biochemical changes, 8, 30, 37–39, 95, 131, 135, 191, 231 Bioengineering, 39, 173, 265, 272, 677–683, 688, 781, 1065 Biogerontology, 487 Biopeptide-CL, 1090 Biopeptide-EL, 1091 Bio-Rejuvenation, 1200–1201 Bio-Restorative skin cream, 1083, 1085, 1110 Biotinyl-GHK, 1090 Bipolar disorder, 963, 967 Bleomycin, 603 Blepharoplasty, 960, 963, 1142, 1147, 1165–1169, 1178–1181 Blood perfusion, 679, 1008 Body area, 31, 350, 357, 827, 829 Body dysmorphic disorder (BDD), 962, 965–967 Body image, 950, 962, 963, 965–967, 1187 Bone marrow stromal cell (BMSC), 202, 203 Botox See Botulinum toxin A Botulinum toxin, 271, 1022, 1112, 1143, 1192 Botulinum toxin A (BTX-A), 915, 960, 963, 967, 1063, 1064, 1067, 1112, 1147–1149, 1152, 1175 Bovine collagen, 471, 1064, 1149, 1150, 1152 Bowen’s disease, 243, 556, 602, 954 See also Squamous cell carcinoma in situ Bradford dye reaction, 404 Brain-derived neurotrophic factor (BDNF), 147, 148, 152 Breast cancer, 97, 260, 365 BRIC economies, 1198 Brick and mortar model, 142, 277, 278, 371, 726, 730 Brittle nails, 240 Browlift, 1140–1142, 1178, 1181 B-scan ultrasound, 681 Buffering capacity, 139–144 Bullous pemphigoid, 40, 82, 121, 136, 534–535 Burns, 11, 159–163, 168, 170, 556, 558, 576, 606, 807, 828, 842, 1020 – hazard, 168 – prevention, 162, 170 Business model, 1193 C Calcium hydroxylapatite (Radiesse1), 1151 Calcium signalling, 513, 514 Calorie restriction (CR), 8–10 Cancer, 8, 37, 80, 94, 131, 152, 184, 193, 228, 260, 323, 365, 415, 428, 430, 455, 487, 503, 509, 531, 545, 567, 579, 587–596, 601–607, 612, 639, 677, 715, 759, 801, 812, 847, 938, 952, 984, 1047, 1055, 1064, 1201 Cancer treatment modalities, 604–607 Capacitance, 173, 176, 179, 378, 688–693, 695, 697–699, 701, 721, 744, 815, 1065, 1111 Carbonyl, 105, 289, 300, 303, 307, 318, 414, 416, 417, 709 Carcinogen, 8, 323, 556, 558, 567, 570, 610, 989 Carcinogenesis, 40, 83, 188, 191, 197, 329, 546, 549, 558, 562, 563, 567–577, 587–592, 594, 610, 781, 990 Cardiolipin, 300, 301, 306 Carnosine, 94, 490 Carrier peptide, 1089, 1090, 1111, 1113 Cartilage Oligomeric Matrix Protein (COMP), 79 Casual level of sebum, 678 Catabolic aging, 51 Caucasian skin, 471, 496, 504–506, 984, 1019–1021, 1023 CBA mouse, CD44, 48, 111, 228, 229, 234, 235, 876 CD71 expression, 194, 196 Cell-mediated immunity, 254–255, 601, 603 Cell-membrane proteoglycans, 111 Cell migration, 131, 904 Cell proliferation, 6, 8, 17, 25, 29, 80, 83, 95, 96, 105, 115–117, 152, 226, 237, 280, 286, 315, 415, 434, 449, 487, 572, 573, 594, 601, 621, 722, 723, 904 Cell rejuvenation serum (CRS), 1081, 1082, 1110 Cell renewal, 350, 371–375, 807 Cell senescence, 286, 287, 487, 1021, 1055–1056 Cell stress, 97, 477 Cellular effects, DNA damage, 327–328 Cellular senescence, 46–47, 93, 129, 301, 588–591, 594, 815, 903, 904, 1021, 1055–1056 Centers for Disease Control and Prevention (CDC), 364, 427, 759 Ceramide, 26, 29, 55–60, 63, 66–68, 70, 140, 142, 214, 250, 279, 371, 401, 413, 506, 642, 648, 654, 687, 695, 699, 706, 709, 725, 736, 745, 811, 814, 815, 826, 828, 833, 834, 930, 934, 999, 1023, 1065, 1075 Cervical inflammation, 255 Changes in vaginal structure, 886 Characteristics, 27, 32, 34, 40, 64, 88, 97, 106, 117, 163, 176, 181, 193, 196, 202, 254, 255, 265–268, 313, 315, 316, 349, 353, 377, 394, 398, 437, 438, 444, 455, 456, 466, 478, 480, 488, 507, 531, 549, 568–569, 601, 604, 607, 641, 688, 689, 707, 751, 781, 801, 802, 818, 829, 834, 837, 845, 850, 861, 876, 880, 883, 926, 930, 936, 950, 959, 973, 974, 977, 992, 999, 1003, 1024, 1047, 1090, 1093, 1109, 1128–1129, 1145, 1166 Subject Index Cheek, 62, 71, 122, 123, 173–181, 218, 219, 268, 334, 337, 378–382, 402, 537, 640, 681, 692, 706, 708, 741, 745, 751, 912, 914, 915, 987, 1082, 1085, 1092, 1139, 1142, 1143, 1149, 1153, 1176, 1178, 1179 Chemical peeling, 607, 708, 1147, 1152–1153 Chemiluminescence (CL), 304, 477, 480–483 Chin, 169, 173–180, 217, 537, 640, 697, 827, 987, 1085, 1110, 1142, 1143, 1148, 1170, Chondroitin sulfate (CS) proteoglycan, 49, 113, 117, 231, 448 Chondroitin sulphate A, 82 Chromophore, 37, 38, 423, 429, 478, 498–500, 569, 749–751, 753, 1020, 1156, 1157, 1159 Chronic cervicitis, 254 Chronic phase of inflammation, 643–644 Chronological age, 14, 300, 316, 329, 363, 374, 385, 698, 921, 959, 966, 973, 977–979, 984 Chronological aging, 5, 13, 14, 16, 48, 51, 101, 102, 113, 191, 231, 232, 266, 282, 286, 287, 315–316, 358, 359, 443, 455, 463–465, 677, 682, 802, 973, 983, 991, 1047, 1065 Cidofovir, 601–603 Circulation, 30, 37, 39, 162, 164, 168, 227, 230, 232, 233, 239, 254, 281, 298, 305, 324, 429, 432, 447, 619–633, 643, 771, 779, 801, 807, 814, 1007 Climacteric aging, 48, 353–359 Climate controlled chamber, 692 Clinical features, 86, 90, 121, 129, 333, 447, 640–642, 817, 964 Clinical implications, 381–382, 528, 594, 596 Clinical models, 510, 516 Clinical signs, 19, 32, 33, 38, 86, 266, 825, 828, 911–917, 934, 991, 1021, 1147 Clonal expansion, 549, 573–574, 589 Cluster of differentiation 1d (CD1d) expression, 183–188 Cockayne syndrome (CS), 96, 325–326, 441, 570 Coculture, 84, 499, 504, 510, 511, 513 CO2 effects, 141–142 Coenzyme Q10, 296, 304, 306–308, 314, 939, 1199 Cold, 32, 160, 166, 168, 281, 282, 379, 506, 531, 604, 630, 679, 692, 722, 790–791, 806, 829, 836, 837, 840, 871, 1007, 1008, 1031, 1036, 1045, 1071, 1155, 1158, 1161 Collagen, 5, 13, 19, 27, 38, 77, 103, 109, 121, 134, 163, 193, 201, 215, 225, 239, 266, 281, 303, 313, 328, 333, 356, 361, 373, 415, 421, 429, 443, 447, 453, 461, 500, 504, 549, 572, 584, 589, 609, 632, 643, 653, 680, 716, 750, 781, 801, 812, 845, 861, 871, 897, 911, 935, 983, 999, 1019, 1027, 1063, 1069, 1079, 1090, 1128, 1147, 1177 Collagen adhesion method, 193 Collagen and polypeptide ingredients, 935 Collagen IV, 13, 15, 49, 81–83, 85, 87–90, 116, 121, 122, 125, 194, 415, 470, 1092 Collagen synthesis, 30, 38, 51, 103–104, 106, 201, 313, 363, 365, 430, 447, 448, 653, 782, 783, 801, 807, 901, 903, 1063, 1067, 1073, 1090, 1091 Collagen XVIII, 111, 116, 117 Colorimetry, 347, 374, 397, 404, 1012 Color of the face, 976, 977 Colour, 752, 1019, 1020, 1022 Comedometry, 396 Commensals, 871, 875, 876, 879, 885, 887 Community composition, 871, 872, 876, 877 COMP See Cartilage Oligomeric Matrix Protein Compensating behaviors, 1125 Complex reconstructed skin, 474 Concentration gradient, 381, 688, 690, 701, 735, 745, 771, 773, 774 Conditioned medium, 77, 124–126, 192, 203 Conductance, 64, 162, 164, 165, 167, 168, 378, 381, 382, 529, 653, 657, 689–693, 697, 721–723, 931, 987, 1010 Confocal Raman spectroscopy, 688, 721, 735–745 Confocal scanning laser microscopy (CSLM), 113, 677, 679, 680, 683, 716, 717 Conjugated linoleic acid (CLA), 216–221, 814 Consumers, 839, 861, 864, 867, 929, 933, 940, 1051, 1053, 1064, 1065, 1122, 1123, 1187, 1188, 1190, 1192, 1194, 1197–1205 Contact allergens, 644–647, 698, 846, 847, 1050 Contact dermatitis, 25, 213, 214, 250, 259, 381, 382, 395, 530, 531, 533–534, 602, 639, 641, 698, 762, 825–830, 833, 834, 837, 846, 933, 935, 1003, 1020, 1048 Copper tripeptide complex, 1093 Corneocytes, 55, 57, 61–71, 377–379, 381, 382, 393–397, 653, 655–657, 705–711, 833, 835 – density analyzer, 405 – size, 55, 64, 70–72, 174, 175, 371–375, 393, 700, 705, 706, 711 Corneofungimetry, 396 Corneomelametry, 395 Corneometer, 690, 691, 744 Corneosurfametry (CSM), 397–398 Corneoxenometry (CXM), 397–398 Cornified envelope, 26, 313, 378, 516, 642, 656, 687, 706–709, 711 Corns, 546 Cosmeceuticals, 271, 272, 432, 437, 490, 929, 1090, 1109, 1113, 1199, 1200 Cosmetic procedures, 45, 915, 959, 963–965, 967, 968, 1022, 1165, 1166, 1168, 1182, 1200 Cosmetics, 127, 203, 240, 244, 271, 378, 393, 660, 682, 709, 829, 845, 851, 863, 916, 929, 935, 937, 940, 954, 1038, 1063–1067, 1089, 1187, 1197–1201, 1204 Cosmetic surgery, 960, 962, 965, 1147–1172 Cosmoderm1, 1149, 1150 Creatine (Cr), 103, 295, 298, 299, 304–305, 307–309, 318 Creatine kinase (CK) activity, 298, 299, 304, 305, 307, 318 Crinkles, 1063 Cross polarization, 840–841 Crow’s feet wrinkles, 911, 913, 914 Cryotherapy, 547, 548, 555, 560, 562, 604–606 Customization, 1200–1201 Cutaneous aging, 11, 25, 48, 129, 137, 147, 270, 295–309, 354, 784, 812, 930, 938–940, 1021, 1056, 1139, 1177 Cutaneous blood vessels, 104, 286, 623, 789, 791 Cutaneous differences, 1007 Cutaneous disease, 545, 949–955 Cutaneous disorders, 385, 538–539, 949 Cutaneous effects, 663–669, 1143 Cutaneous malignant melanoma (CMM), 558, 559, 579, 613 Cutaneous pigmentation, 388–390, 938 Cutometer, 912 Cyanoacrylate skin surface stripping (CSSS), 347, 393–398 Cyclobutane dimer, 569, 570, 572, 575, 577 Cyclobutane pyrimidine dimer (CPD), 104, 323–329, 453, 454, 509, 569 Cypridina luciferin analog (CLA), 216–221, 481, 482, 643, 814 Cysts and lacuna, 134 Cytokine mediators, 841–842 Cytokines, 13, 17, 112, 122, 154, 181, 183, 188, 201, 203, 214, 215, 227, 231, 232, 255, 280, 281, 289, 328, 329, 385, 389, 403, 413, 423, 448, 471, 488, 562, 572, 573, 589–592, 601, 603, 626, 629, 631, 640, 643, 646, 649, 709, 711, 790, 793, 803, 811, 817, 825, 826, 901–904, 930, 936, 939, 1056–1059, 1079–1086, 1110 D Dansyl chloride, 173, 174, 195, 371, 700 DBD scoring, 14, 19–21 Decorin, 49, 50, 109, 112–114, 117, 448, 1091 Decubitus ulcers, 1132–1134 Deep peels, 1152, 1153–1154 Defective powerhouse model, 103, 105–106 Defensin, 247, 254, 255, 644, 709, 711, 1057 Depression, 269, 393, 444–446, 611, 646, 647, 668, 761, 935, 949–952, 954, 955, 960–964, 966, 967, 1143, 1146, 1177 Dermabrasion, 938, 1021, 1147, 1154–1156, 1200 DermaLab Moisture Unit, 691 Dermal absorption, 771–776, 778, 779, 849, 850, 859 Dermal basophilic degeneration (DBD), 14, 17, 19–21 Dermal infection, 666–667, 1132 Dermal proteoglycans, 113, 114 Dermal safety, 857–867 Dermatitis, 25, 41, 105, 136, 173, 213, 232, 250, 255, 259, 279, 344, 378, 395, 415, 530, 591, 602, 626, 639–649, 654, 663, 698, 706, 723, 725, 759, 803, 811, 825–830, 833, 846, 876, 1209 1210 Subject Index 933, 952, 988, 1003, 1020, 1048, 1089, 1131–1132, 1158 Dermatology, 5, 38, 41, 46, 213, 214, 304, 393, 427, 530, 533, 535–537, 545, 546, 604, 614, 640, 683, 688, 718, 757, 761–766, 826, 828, 830, 916, 921, 929, 949, 951, 952, 954, 965, 991, 992, 1056, 1089 Dermatotoxicology, 853 Dermis, 6, 13, 19–21, 25, 37, 45, 56, 77, 93, 101, 109, 121, 130–132, 140, 148, 160, 173, 183, 191, 203, 213, 225, 240, 265, 277, 297, 313, 323, 333, 353, 363, 371, 377, 393, 401, 413, 421, 429, 447, 453, 461, 477, 496, 504, 511, 527, 545, 567, 579, 587–596, 606, 631, 643, 665, 677, 687, 695, 709, 716, 750, 759, 771, 782, 789, 801, 815, 825, 833, 845, 871, 897, 911, 933, 984, 999, 1021, 1027, 1066, 1069, 1080, 1090, 1177 Desquamation, 29, 55, 59, 61–63, 66, 70, 72, 130, 140, 289, 357, 359, 371, 372, 375, 401, 414, 516, 573, 606, 678, 700, 708, 735, 737, 742, 744, 814, 825, 836, 842, 930, 931, 984, 988, 1065 Desquamative inflammatory vaginitis (DIV), 257 Detergents, 141, 232, 641, 642, 645, 721, 737, 826, 827, 863, 931, 933 Diabetes, 14, 88, 132, 137, 168, 241–243, 295, 303, 582, 619–633, 653–660, 791, 812, 904 Diabetes mellitus, 13, 88, 168, 242, 243, 582, 653–660 Diagnostic criteria, 639–642, 965 Diagnostic tests, 646–647 Dichlorodihydrofluoresceindiacetat (DCHFDA), 304 Diclofenac, 548, 601–603 Diet, 51, 94, 287, 418, 436, 607, 644, 647, 775– 777, 782, 802, 883, 932, 966, 973, 1055, 1058, 1059, 1166, 1175 Diet (BMI), 443–446, 633 Dietary and herbal effects, cancer, 607 Differences, 21, 27, 48, 55, 84, 140, 159, 173– 181, 192, 202, 217, 229, 265, 284, 297, 315, 326, 343, 357, 365, 372, 377, 386, 393, 401, 415, 422, 441, 471, 483, 488, 503, 510, 577, 581, 611, 626, 639, 677, 689, 697, 707, 715, 725, 738, 759, 773, 784, 802, 825, 833, 846, 861, 872, 902, 911, 925, 933, 960, 973, 983, 999–1015, 1019–1021, 1028, 1047, 1080, 1111, 1147, 1189, 1203 Digital photograph, 751, 922, 1081, 1082 Dilated pore, 206, 208, 209 Dimethylaminoethanol (DMAE), 1074, 1199 Disposable diapers, 857–867 Dissociative disorder, 967–968 Distinguishability, 922–925 DNA – biomarkers, 453–456 – damage, 8, 49, 95, 101, 104, 106, 129, 286, 288, 289, 323–330, 357, 430, 453, 454, 477–479, 509, 546, 562, 567, 569, 570, 572–574, 576, 577, 581, 582, 587–589, 591–595 – mutation, 324, 545, 587–589 – repair, 93, 94, 97, 101, 104, 129, 197, 288, 300, 313, 318, 323–326, 328–330, 441, 545, 546, 558, 559, 569, 570, 572, 575–577, 579, 581–583, 587, 589, 594, 983, 1109 Dose-response assessment, 857 Dreher’s colorimetric method, 404 Drosophila, 95, 192, 314 Drug etiology, 539 Dry skin, 25, 55, 63, 65–70, 349, 357, 364, 378, 379, 396, 453, 527–530, 640–642, 653–660, 665, 687, 688, 690, 700, 707, 709, 717, 735, 744, 758, 825, 829, 851, 930, 932–934, 937, 949, 1065, 1132 Dysbiosis, 812, 879, 880 E Eating disorder, 966 Eccrine sweat, 141–143, 282, 504, 697 ECM1 See Extracellular matrix protein Eczema, 40, 395, 527, 530–531, 534, 639–647, 649, 687, 762, 765, 792, 803–805, 807, 827, 828, 830, 877, 951, 952, 954, 1003, 1013 – subtypes, 828 Effect of occlusion, 664, 846 Elafin, 254 Elastic fibers, 5, 6, 8, 9, 19, 49, 52, 134, 135, 163, 266, 267, 283, 333, 334, 336–339, 356, 364, 447, 448, 453, 682, 789, 898, 1021 Elasticity, 27, 30, 34, 49, 97, 114, 135, 162, 231, 257–259, 265, 269, 271, 282, 283, 285, 316, 329, 357, 361, 363, 364, 366, 429, 430, 444, 448, 591, 613, 664, 677, 692, 699, 759, 782, 801, 805, 845, 912, 913, 917, 938, 976, 984, 1002, 1003, 1021, 1023, 1027, 1047, 1063, 1092, 1111, 1131, 1153, 1164, 1165, 1170, 1177, 1179, 1181 Elastin, 6, 8, 9, 27, 28, 30, 38, 39, 48–50, 96, 103, 104, 133–135, 225, 226, 231, 283, 303, 333–338, 354, 356, 363, 415, 421, 448, 464, 471, 537, 590, 716–718, 781, 784, 801, 802, 816, 845, 897, 911, 939, 984, 988, 1019, 1023, 1063, 1081, 1090, 1092, 1111, 1128, 1147 Elderly, 5, 13, 25, 37, 48, 65, 93, 131, 139–144, 159–170, 177, 191, 230, 239, 271, 284, 303, 357, 361, 371, 379, 403, 416, 427, 443, 455, 527, 545–563, 568, 581, 601, 613, 639, 659, 663, 677, 687, 696, 707, 736, 771, 801, 816, 825, 833–842, 845–853, 857–867, 879, 898, 949, 988, 1008, 1023, 1027, 1047, 1055, 1080, 1089, 1131, 1147–1172 Elderly skin function, 139–140 Elderly women, 362, 536, 681, 683, 891, 1012, 1045 Electrodesiccation and Curettage (ED&C), 604–605 Electron paramagnetic resonance (EPR), 725–733 Electron spin resonance (ESR), 477, 480–481, 725 Emollients, 240, 393, 531, 648, 687, 692, 935, 954, 1065 Emotion, 130, 628, 640, 646, 762, 764, 911, 954, 959, 963, 979, 1187 Emotional symptoms, 950 Endochondral bone formation, 79 Endocrine aging, 50–51 Endocrinology, 366 Endogenous aging, 93–98 Endothelial cells (EC), 14, 15, 17, 45, 80, 81, 83, 111, 115, 226, 227, 296, 298, 471, 619–631, 646, 789–793, 898, 899, 903, 904, 1080, 1086, 1158 Endothelial function, 629–631, 904 Endothelial nitric oxide synthetase (ENOS), 620–622, 624, 625, 628–631 Endothelin‐1 (ET‐1), 13, 385–390, 496, 516, 574, 790, 791, 793 Energetic factors, 295–299 Energy metabolism, 103, 295–309, 313–318 Environmental factors, 5, 93, 98, 101, 147, 175, 213, 282, 289, 441, 453, 527, 581, 587, 629, 631, 639, 642, 644, 677, 722, 781, 812, 814, 817, 880, 911, 917, 921, 1031–1038 Environmental insult, 323, 328, 453, 455, 527, 545 Enzyme inhibitor peptides, 1090, 1111–1112 Enzyme-linked immunosorbent assay (ELISA), 81, 83, 385–388, 390, 449, 708 Epidemiology, 287, 567, 579–581, 639 Epidermal barrier, 213, 214, 279, 280, 284, 285, 364, 366, 403, 594, 643, 725, 814, 825–827, 829 Epidermal homeostasis, 90, 148–152, 215, 221, 280, 573, 592 Epidermal permeability barrier, 213, 373, 697, 826 Epidermal proteins, 132–133, 536 Epidermal stem cells, 11, 191–197, 277, 278, 573, 722, 1056, 1156 Epidermal thickness, 6–8, 19, 25, 28, 130, 163, 283, 363, 609, 611–613, 699, 719, 723, 985, 991, 1027, 1047, 1109, 1110, 1153 Epidermis, 6, 15, 19, 25, 37, 49, 56, 77, 93, 101, 109, 121, 130–132, 140, 148, 160, 176, 183, 191, 203, 213, 225, 266, 277, 297, 313, 326, 334, 353, 371, 377, 393, 401, 413, 422, 432, 447, 453, 462, 477, 496, 504, 511, 527, 545, 573, 579, 587, 609, 653, 665, 677, 687, 695, 706, 715, 735, 759, 771, 782, 790, 800, 814, 833, 871, 897, 914, 931, 999, 1019, 1069, 1089, 1127, 1147, 1189 Epithelial membrane antigen (EMA), 344 Epithelium, 8, 83, 116, 137, 143, 153, 194, 204, 239, 243, 247, 250, 255, 344, 417, 536, 837, 884, 886, 888, 987, 1126, 1127, 1129 Escherichiae coli, 257 Esterase, 708, 709 Subject Index Estradiol, 31, 32, 130, 355, 363–366, 698, 776, 778, 779, 834, 849, 1013, 1128 Estrogen, 38, 51, 97, 237, 248, 253, 257, 281, 350, 354, 361–366, 372, 434, 444, 497, 504, 516, 622, 678, 884, 983, 1008, 1121, 1127, 1177 Estrogen deficiency, 255, 357, 359, 362, 363, 987 Estrogen replacement therapy (ERT), 259, 361, 444 Ethanol, 178, 329, 394, 774, 791, 1059 Ethnic, 350–351, 390, 471, 474, 503–507, 510, 512, 516, 534, 558, 630, 639, 851, 886, 913, 1019, 1021, 1028, 1033, 1203 Ethnic differences, 208, 390, 503, 984, 1021, 1031 Ethnicity, 49–50, 265, 351, 503–505, 510, 527, 581, 878, 883, 983–994, 1021, 1028, 1051, 1189 Ethnic skin type, 49, 506, 507, 510 Ethnopharmacology, 234, 237 Evolence1, 1150 Evolutionary psychologists, 751 Excision repair, 39, 102, 288, 324–325, 328, 329, 546, 570, 572, 576, 577, 582 Exfoliating agents, 938 Experimental models, 118, 302, 328, 627, 653–660 Exposure, 14, 19, 32, 37, 47, 64, 97, 102, 114, 121, 129, 140, 147, 160, 173, 208, 215, 231, 243, 253, 265, 288, 305, 323, 333–339, 354, 363, 374, 389, 411, 423, 427, 429, 442, 447, 453, 461, 477, 495, 503, 509, 527, 545, 567, 579, 587, 609–614, 625, 640, 664, 677, 698, 709, 727, 736, 758, 771, 781, 789, 802, 812, 825, 836, 845–853, 857, 872, 897, 911, 921, 931, 967, 973, 983, 999, 1019, 1048, 1056, 1063, 1070, 1081, 1109, 1142, 1147, 1175, 1198 Exposure assessment, 851–853, 857, 861, 862, 865–867 Expression, 11, 13, 39, 49, 59, 77, 93, 103, 123, 129, 139, 147, 179, 183, 191, 201, 213, 227, 254, 267, 279, 298, 316, 333, 385, 415, 421, 429, 448, 496, 511, 532, 554, 573, 587, 642, 656, 708, 735, 782, 790, 801, 814, 825, 898, 911, 921, 931, 959, 979, 989, 1021, 1050, 1055, 1066, 1069, 1092, 1147 Exsiccation eczematoid, 828 Extracellular matrix (ECM), 38, 39, 78, 79, 81, 87, 88, 96, 103, 105, 112–115, 117, 121, 122, 131, 133, 192, 201, 215, 221, 225, 271, 280, 283, 303, 313, 317, 333, 356–357, 415, 421, 429, 443, 448, 449, 461, 466, 468, 470, 471, 532, 573, 591, 718, 782, 783, 789, 790, 801, 806, 815, 833, 897, 988, 1067, 1069, 1079, 1082, 1092 Extracellular matrix protein (ECM1), 77–90 Extramitochondrial energy stores, 298–299 Extrinsic aging, 25, 37, 49, 86, 106, 129, 147, 162, 265, 295, 302, 304, 315–317, 441, 443, 445, 677, 749, 771, 812, 877, 897, 938, 939, 983, 1021, 1056, 1080, 1147, 1169 Extrinsic facial aging, 441, 445 Extrinsic factors, 13, 95, 173, 191, 192, 441, 739, 771, 837, 891, 959, 988–992, 1056 F Face lifts, 960, 961, 966, 968, 1169–1172, 1179– 1181 Facial aging, 266, 441–445, 916, 972, 990, 1023, 1081, 1138–1139, 1144, 1146, 1181 Facial area, 181, 350, 682, 683, 1027, 1029, 1151 Facial beauty, 235, 1190, 1193 Facial clinical, 516, 913 Facial plastic surgery, 916, 961, 968, 1139 Facial rejuvenation, 962, 965, 968, 1021, 1024, 1139, 1147, 1154, 1175–1182 Facial skin, 8, 9, 32, 52, 69, 148, 173, 176–180, 265–272, 357, 377–381, 504, 516, 518, 538, 681, 683, 706, 707, 751, 790, 878, 911, 914, 921, 922, 929, 936, 959–961, 973–980, 983, 989, 1027–1029, 1031, 1043, 1069, 1071, 1074, 1075, 1085, 1089, 1109, 1110, 1113, 1154, 1170, 1182, 1187–1194 Facial wrinkles, 130, 209, 447, 790, 911, 914, 1069, 1072, 1073, 1083, 1085, 1175 Family history, 547, 558, 579, 614, 641, 1031, 1036 Fat grafting, 1140, 1143, 1144 Fat transfer, 1139–1145, 1179, 1180, 1182 Fecal incontinence, 663–667, 759, 829, 857, 1132 Federal Food, Drug, and Cosmetic Act, 1063 Female, 6, 19, 122, 163, 206, 216, 247, 253–257, 285, 334, 355, 372, 378, 442, 497, 516, 580, 609, 627, 640, 663, 677, 698, 745, 751, 774, 782, 830, 837, 849, 883, 912, 921, 960, 974, 999, 1022, 1028, 1071, 1081, 1092, 1121– 1125, 1127, 1143, 1166, 1193 Fibrillin, 49 Fibroblasts, 82, 93, 110, 124, 125, 151, 204, 266, 356, 385, 386, 389, 449, 462, 465–470, 473, 489, 591, 595, 801, 807, 902, 1073 Fibronectin, 82, 87 Fibulin 3, 82, 87 Fibulin‐5, 333–339 Fibulin 1C/D, 82, 87 Filaggrin, 65, 278, 654, 931 Fillers, 1149–1152, 1176, 1179 Fine line, 217–219, 1071, 1074 Finite dosing, 774, 775 Fischer 344 rats, 7–9, 774 Fitzpatrick skin phototype system, 1020 Flow-through cells, 774 Fluorescence, 14, 15, 479–480, 722 5-Fluorouracil (5-FU), 602, 603, 607 Follicular excretion rate (FER), 349, 350 Food allergens, 640, 643, 644, 646, 1051 Forehead, 123, 173–175, 178–180, 268, 343, 345, 348, 351, 372, 374, 380, 381, 401, 537, 657–659, 677–679, 681, 682, 692, 696, 697, 699, 731, 801, 871, 872, 879, 911, 914, 915, 959, 963, 978, 987, 999, 1003, 1012, 1064, 1112, 1146, 1148, 1149, 1175, 1177, 1200 Fractional CO2 laser, 209–211 Franz cells, 775 Free amino acids, 65, 141–143, 706, 707, 931 Free fatty acids, 26, 65, 140, 279, 284, 343, 345, 371, 401, 403, 413, 621, 631, 695, 699, 709, 725, 736, 737, 814, 932 Free radicals, 8, 38, 40, 129, 203, 204, 225, 231, 286, 288, 301, 302, 317, 412, 413, 417, 418, 443, 461, 583, 591, 631, 726, 727, 790, 801, 802, 805, 807, 815, 936, 1055, 1056, 1109 Free radical theory, 93–94, 289, 299, 314, 418, 815 Frictional coefficient, 826 Function, 6, 13, 25, 37, 45, 55, 77–90, 93, 101, 109, 121, 130, 139, 147, 163, 173, 183, 191, 201, 213, 225, 243, 250, 253, 257, 265, 277, 296, 313, 323, 333, 343, 361, 371, 377, 393, 401, 412, 422, 429, 448, 455, 461, 477, 488, 495, 503, 509, 527, 545, 570, 582, 587, 603, 609–614, 620, 642–643, 653, 664, 683, 687, 695, 705, 715, 725, 735, 757, 771, 789, 800, 814, 827, 833, 845, 859, 875, 886, 897, 911, 924, 929, 949, 962, 983, 1002, 1019, 1027, 1047, 1055, 1063, 1071, 1081, 1090, 1121, 1131, 1166, 1179, 1188 Functional changes, 37, 94, 101, 127, 164, 282, 357, 659, 677, 758, 879 Functional differences, 506, 853, 1003–1007 Functional loss, 16, 83, 1021, 1023–1024 Functional properties of the stratum corneum, 381, 653, 654, 659 Functional psycho-neuro-muscular system, 130 Fungal infections, 258, 666, 880, 1132 Fungus, 427 G Gender, 28, 163, 175, 241, 265, 343, 353, 386, 527, 558, 611, 619–633, 646, 663, 707, 846, 934, 960, 973, 983–994, 999–1015, 1028, 1051, 1142 – bias, 974–975 – differences, 179, 386, 387, 626, 646, 960, 983, 999–1015 Generalized pruritus, 51, 529, 762, 829 Genetic aging, 48 Genetic polymorphisms, 326, 631, 848 Genetics, 87, 228, 282, 505–506, 518, 771, 804, 938, 1142 Genetic variability, 846 Genital area, 536, 667–669, 838, 988, 1027, 1029, 1030, 1038–1043 Geriatric, 241, 533, 587, 590, 592, 594, 595, 665, 669, 759, 761, 830, 836, 867 1211 1212 Subject Index Gerontology, 677, 858, 1056 GHK-Cu peptide, 1090, 1113 Global heat, 624, 625, 628 Globalization, 1203, 1204 Global skin care market, 1197, 1202 Global warming, 427–428 Glucosamine, 498, 499, 939 Glutathione (GSH), 47, 204, 231, 281, 286, 288, 298, 299, 306, 314, 317, 327, 414, 422, 477, 481, 482, 505, 554, 571, 576, 709 Glycation, 8, 307, 308, 463–465, 468, 474, 499, 709, 790, 1111, 1149 Glycolysis, 247–250, 286, 295, 297, 298, 301, 307 Glycosaminoglycans (GAGs), 27, 30, 109, 112, 225–228, 231, 236, 283, 356, 364, 453, 471, 897, 1069, 1071, 1073, 1097, 1146 Glyphic wrinkles, 1063 Glypicans, 111, 114–116 Governance, 1203–1205 Granulocyte macrophage colony stimulating factor (GM-CSF), 8, 328, 385–387, 643, 825 Gravitational aging, 51 Gravitational eczema, 530, 532–533 Grief, 960, 961 Group A streptococci, 876, 880 Growth factors, 13, 85, 97, 105, 112, 122, 137, 147, 162, 201, 225, 280, 403, 423, 487, 582, 589, 622, 656, 807, 826, 899, 939, 1056, 1074–1075, 1079–1086, 1092, 1199 H HaCaT, 305, 316, 512–514 Hayflick lmit, 132, 487, 490 Hayflic system, 490, 491 Hazard identification, 857, 862 HbA1C, 657–659 Health related quality of life (HRQoL), 639, 759–766 Heat shock proteins, 227, 414–415, 623, 1057, 1110 Helio dermatitis, 105 Hemoglobin, 500, 503, 716, 749–751, 753, 1012, 1020, 1156, 1157 Heparan-sulfate proteoglycans (HS-PGs), 116–117 Hepatocyte growth factor (HGF), 152, 203, 204, 385, 386, 389, 575, 1110 Hexapeptide–11, 1092 Hexyl nicotinate (HN), 178–179 High-frequency conductance (HFC), 378, 381, 653, 657, 659, 691, 693 High frequency impedance, 378 High frequency instrument, 689 Histological scoring approach, 19–21 Histopathology, 643 HMG-CoA reductase, 404, 695, 699, 826 HMG-CoA reductase activity, 404, 699 HMG-CoA reductase inhibitor, 829 Hoechst dye exclusion, 191, 193 Homoplasmy, 455 Hook constant, 268 Hormesis, 491 Hormetins, 491 Hormonal aging, 97 Hormonal changes, 357, 374, 495, 682, 883, 884, 911, 988 Hormonal regulation, sebum, 349–350 Hormone, 37, 50, 93, 213, 247–248, 253, 257, 281, 343, 354, 363, 371–375, 506, 516, 619, 646, 655, 677, 722, 791, 878, 884, 916, 932, 983, 999, 1021, 1056, 1074, 1109, 1127, 1200 Hormone replacement therapy (HRT), 51, 97, 255, 257–260, 353–359, 361, 372, 374, 442, 444–446, 887–891, 916, 983, 1013, 1129, 1132 Host health, 875–876 Hot flashes, 257, 361 Household products, 1036, 1038–1040, 1043 Human safety, 845, 859, 865 Human skin, 5, 13–17, 25, 39, 48, 61, 81, 97, 102, 113, 122, 132, 143, 148, 183, 194, 210, 225, 254, 277, 295, 315, 323, 333–339, 349, 354, 362, 396, 401, 415, 421, 429, 449, 453, 467, 477, 489, 495, 503, 509, 573, 588, 643, 656, 683, 687, 695, 739, 749, 773, 781, 791, 800, 812, 846, 871, 898, 931, 991, 1056, 1066, 1080, 1089 Human skin equivalent models, 124, 477–484 Humectants, 721, 736, 933–935, 1065, 1132 Humoral immunity, 253–256, 816, 1059 Hutchinson–Gilford progeria syndrome (HGPS), 129, 441 Hyaladherins, 228, 229, 232, 233, 235 Hyalectans, 109 Hyaluronan, 82, 114, 225–237, 801 Hyaluronan oligomers, 227–228 Hyaluronan synthase, 232 Hyaluronasome, 234–235 Hyaluronic acid (HA), 26, 27, 30, 51, 65, 82, 109, 111, 112, 225, 283, 356, 364, 365, 448, 806, 807, 932, 1079, 1092, 1149, 1150, 1152, 1176–1178, 1199, 1200 Hyaluronidase, 227, 229, 230, 232–237 Hyaluronidase inhibitors, 233–236 Hydration state, 176, 377–379, 382, 659, 688–690, 692, 693, 697, 739 Hydrocortisone, 31, 32, 179, 237, 385, 698, 775–778, 834, 837, 849, 1128 Hydrogen peroxide (H2O2), 38, 46, 47, 204, 253, 288, 291, 299–301, 314, 357, 413, 416, 419, 453, 454, 477, 480, 569, 590, 789, 812, 884, 885 Hydroquinone, 498, 938, 1020–1022, 1063–1065, 1152, 1198 Hydroxy acids, 934, 1065, 1199 8-Hydroxy–20 -deoxyguanosine (8-OHdG), 289, 477–479, 569 8-Hydroxyguanine, 453, 454 Hydroxyl radical (OH), 38, 46, 231, 288, 299, 411, 477, 480, 482, 569, 1109 Hygroscopicity, 689 Hyperfine coupling, 728 Hyperpigmentation,216, 325, 495–500, 509, 516–518, 533, 603, 784, 937, 938, 966, 1019, 1020, 1022, 1024, 1069, 1070, 1109, 1113, 1153, 1154, 1161 Hypoxia, 131, 298, 307, 631, 901 Hysteresis, 267, 269, 270 I I-CAM 1, 791 Ideal reconstructed skin, 473 Identical twins, 442, 443, 914, 915,932 IgA, 247, 253, 649, 1059 IgG, 85, 88, 247, 253, 536, 1059 Image analysis (IA), 114, 269, 346, 347, 374, 394, 396, 398, 497, 499, 682, 683, 749, 913, 914, 916, 1074, 1076 Imaging, 258, 284, 375, 479–481, 629, 683, 707, 716–718, 737, 749, 750, 752, 913–915, 984, 1189 Imidazoquinoline, 601–602 Imiquimod, 243, 548, 554, 577, 595, 596, 601– 603, 605 Immune function, 131, 139, 140, 191, 253–256, 281, 285, 286, 575, 576, 581–583, 589, 664, 803, 806, 816, 829, 846, 879, 880, 936 Immune modulation, 803, 804, 871, 876 Immune response, 33, 37, 131, 163, 253–255, 281, 285, 546, 581, 591, 621, 643–645, 666, 803, 807, 816–817, 825, 846, 876, 877, 936, 1047, 1051, 1058, 1059, 1132 Immune suppression, 255, 328, 329, 574, 589, 805, 807 Immunosenescence, 582, 817, 1055, 1058, 1059 Incontinence, 25, 537, 663–669, 759, 829, 851, 857, 859, 890, 891, 988, 1028, 1043–1045, 1121–1125, 1130–1133 Incontinence dermatitis, 663, 665–667, 759, 829, 1131–1132, 1134 Incontinence hygiene, 537, 988, 1124 Incontinent market, 1124 Increasing sensitivity for the elderly, 842 Infant, 159, 241, 248, 253, 695, 696, 715–720, 722–723, 737, 745, 772, 803, 804, 878, 1051, 1055 Infinite dosing, 773, 774, 1067 Inflammation, 19, 32, 213, 226, 242, 254, 258, 281, 315, 390, 401, 413, 439, 477, 496, 530, 589, 621, 640, 655, 663, 698, 708, 759, 790, 802, 812, 825, 841, 898, 932, 991, 1019, 1047, 1055, 1079, 1130, 1159 Inflammatory scaling dermatoses, 530–534 Infrared A (IRA), 47–49, 317, 421–424, 705, 707 Infrared lasers, 1157, 1159, 1160 Infrared radiation, 47, 265, 271, 327, 354, 421–424 Subject Index Infrared thermographic, 841, 842 Ingrown toe nail, 242–243 Injury, 30, 33, 34, 37, 47, 48, 84, 101, 123, 140, 159–170, 195, 201, 202, 214, 215, 227, 281, 354, 361, 362, 390, 401, 417, 418, 420, 477, 506, 534, 537, 583, 606, 607, 633, 663–665, 667, 722, 792, 793, 817, 842, 899, 901, 1019, 1020, 1023, 1057, 1079, 1131, 1152–1154, 1159, 1160, 1189 Injury response, 30, 33, 281, 583, 792 Instant sebum delivery (ISD), 348–349 Insulin, 48, 96, 97, 385, 429, 592–594, 596, 621, 622, 627–631, 653, 655–657, 659, 708, 902, 1089 Insulin-like growth factor (IGF‐1), 51, 97, 350, 587, 589, 591–596, 904, 1056, 1082, 1109 Insulin-like growth factor receptor (IGF1-R), 587, 591–595 Integrin a6brightCD71dim method, 193, 194, 196 Integrin receptors, 574, 825 Intense pulsed light instruments (IPLs), 1023, 1159–1161 Intercellular lipids, 26, 60, 278, 371, 377, 378, 401, 402, 654, 655, 687, 695, 699, 705, 706, 711, 725, 729, 730, 732, 736, 815, 834 Intercellular route, 771 Interferon-a (IFN-a), 601, 603, 604 Interleukin 1, 85, 95, 96, 214, 258, 280, 709, 826, 1082 Interleukin–1a (IL‐1a), 49, 328, 385–390, 401, 403, 710, 711, 792, 826, 842, 1082 Intertrigo, 663, 667, 759, 1132 Intracellular adhesion molecule, 789, 825 Intralesional agents, cancer, 603 Intrinsic aging process, 5, 6, 9, 11, 25, 29, 37, 38, 47, 96, 121, 129–137, 147, 162, 163, 214, 270, 271, 283, 295–297, 301, 333, 441, 443, 461, 771, 781, 783–784, 897, 921, 938, 939, 959, 973, 983, 992, 993, 1021, 1056, 1080, 1147 Intrinsic cellular modifications, 191 Intrinsic facial aging, 266, 441–446, 916, 962, 976, 990, 1023, 1081, 1139–1140, 1145, 1147, 1182 Intrinsic factors, 50, 191, 445, 461, 711, 921, 983–988, 992, 1109 Intrinsic metabolism, 323 In vitro/in vivo models, tobacco smoke, 447–449 In vitro model, 97, 195, 461–474, 738, 781, 1056 In vivo epidermal repopulating unit, 194, 196 In vivo model, 500 In vivo water sorption-desorption test, 689, 690 Irritant contact dermatitis – irritants, 825–830 – subtypes, 828, 829 Irritant dermatitis, 173, 181, 418, 646, 725, 828, 829, 836, 846, 1003, 1005, 1050 Irritant reactions, 647, 828, 837, 838 Irritant response, 32–33, 698, 836, 837, 846, 1028 Irritation, 32, 37, 136, 179, 214, 231, 259, 393, 406, 547, 602, 640, 664, 697, 711, 759, 825, 833, 845, 864, 937, 987, 1005, 1027, 1048, 1067, 1069, 1109, 1124, 1127, 1189 Itch severity scale, 764 Itchy, 34, 55, 529, 532, 640, 641, 764, 949, 955, 1132 Itchy QoL, 764 J Jawline tuck procedure, 1169–1172 Juvenile phase, 16 K Kallikrein, 62, 63, 66, 70, 337, 708 Kappa, 95, 631, 759, 921, 922, 924–927 Keratin, 11, 26, 60, 64, 81, 96, 115, 132, 141, 142, 144, 193, 196, 258, 277, 278, 313, 393, 401, 414, 471, 531, 556, 656, 657, 668, 695, 706, 709, 716, 717, 736, 801, 806, 814, 911, 1071, 1111 Keratinocytes, 8, 19, 25, 37, 45, 61, 77, 93, 101, 110, 121, 130, 148, 163, 181, 183, 193, 203, 213, 228, 240, 277, 295, 313, 326, 371, 385, 396, 401, 414, 423, 429, 453, 461, 479, 487, 495, 503, 509, 527, 547, 571, 587, 602, 609, 653, 687, 708, 717, 735, 790, 801, 825, 871, 897, 930, 983, 1074, 1079, 1090, 1147 Keratoacanthoma, 556, 603–606 Keratolytic bioassay, 405–406 Kinetin (KN), 490, 784, 1074, 1077, 1109 Kinetin (N6-furfuryladenine), 1074, 1109 Kitchen logic, 1190, 1194 Kligman, A.M., 55, 174, 371, 379, 421, 429, 698, 772, 782, 911, 912 Kyphosis, 102, 300, 302 L Lactate, 66, 235, 247–250, 297, 298, 304, 529, 655, 660, 687, 736, 737, 745, 934, 1003 Lactic acid, 32, 141–143, 235, 247, 248, 253, 371, 668, 698, 735, 737, 811, 812, 837, 846, 876, 883–886, 891, 931, 934–935, 937, 1027, 1048, 1050, 1065, 1075, 1149, 1151, 1153 Lactobacilli, 248, 250, 253, 257–259, 811, 812, 814, 816, 883–888, 890, 891 Lactobacillus, 247–250, 253, 799, 803, 805–807, 812, 814, 818, 883–886, 888–891 Lam,S.M., 1139–1145 Lamellar granules (LG), 62, 277, 278, 1065 Laminin 332, 81–85, 87–90, 121, 122, 125–127 Langerhans cells, 5, 7, 25, 29, 33, 39, 105, 111, 112, 131, 228, 254, 255, 281, 285, 297, 328, 423, 430, 533, 546, 583, 589, 591, 643, 718, 791, 801, 805, 817, 846, 871, 879, 897, 991, 1023 Laser ablation, 604, 606–607 Laser blood flow, 173 Laser doppler flowmetry (LDF), 165, 166, 173– 175, 177, 178, 679, 783, 1008 Leg ulcers, 131, 137, 357, 533, 606, 955 Lentigo maligna, 558, 567, 568, 577, 583–585, 602, 605, 606 Lentigo maligna melanoma, 558, 567, 568, 583–585 Lentigos (lentigenes), 132, 390, 495–497, 500, 516, 518, 547, 585, 937, 940, 1022, 1023, 1056, 1113, 1159 Leprecan, 117 Leukoplakia, 536 Lichen sclerosis (LS), 258, 534, 536 Lichen sclerosus, 81, 85–89 Life event, 950 Life expectancy, 8, 25, 37, 93, 300, 325, 353, 361, 461, 576, 579, 765, 845, 983, 1055, 1197 Lifespan, 25, 30, 135, 136, 162, 282, 302, 389, 487–491, 509, 590, 774, 784, 883–890, 950, 1055 Lifestyle, 25, 48, 129, 137, 257, 259, 354, 421, 441, 442, 531, 554, 629–631, 639, 660, 789, 790, 916, 950, 973, 983–994, 1056, 1164, 1189, 1197, 1198 Lifestyle influences, 25, 129, 137, 983–994 Light amplification stimulated by emission of radiation (LASER), 39, 113, 165, 173, 203, 478, 498, 596, 604, 629, 677, 716, 738, 783, 817, 836, 915, 984, 1008, 1019, 1147, 1175, 1189, 1200 Linear furrows, 1063 Linewidth, 728, 730 Lip, 86, 169, 349, 357, 380, 447, 547, 562, 569, 606, 619, 679, 681, 801, 978, 980, 987, 1023, 1111, 1149–1151, 1176, 1177, 1179 Lipid composition, 26, 68, 279, 300, 344–345, 351, 401, 700, 701, 779, 814–815, 987 Lipid content/sebum production, 142–143 Lipid content skin surface (sebum), 173 Lipids, 8, 26, 37, 55, 94, 104, 135, 140, 173, 183, 192, 213, 230, 239, 260, 277, 298, 314, 327, 344, 358, 364, 371, 377, 393, 401, 413, 434, 453, 477, 488, 506, 527, 569, 589, 627, 642, 653, 663, 678, 687, 695, 705, 718, 725, 735, 771, 801, 812, 825, 833, 849, 871, 930, 983, 999, 1019, 1057, 1065, 1071, 1111 Lipoaugmentation, 271, 1180 Lipoid proteinosis, 79, 81, 83–90 Lipopentapeptide, 1067, 1110 Liposuction, 201, 202, 959, 1147, 1162–1165, 1169, 1171, 1180 Lipotransfer, 1179–1181 Live microorganism, 799, 811, 812, 817 Local heating, 165, 168, 623–625, 627–629, 1008 LOHAS, 1197, 1198 Longevity, 130, 132, 315, 361, 589, 592, 1055, 1144, 1149–1151, 1179, 1181, 1194, 1200 Longitudinal study, 917, 950 Long-lasting biodegradable fillers, 1151 Loricrin, 279, 371, 378, 656 Lowry’s method, 404 1213 1214 Subject Index Lumican, 109, 112–114, 1097 Luminance, 678, 749 M Macromolecular metabolism, 447 Macrophages, 109, 112, 255, 281, 385, 413, 415, 417, 496, 497, 546, 590, 643, 782, 789, 790, 897–901, 1110 Major histocompatibility complex (MHC) molecules, 183, 642, 900 Malassezia, 343, 395, 534, 645, 646, 801–803, 813, 872, 877–879 Malignant melanoma (MM), 395, 396, 545, 556–561, 569, 579, 581, 610, 613, 614, 750, 759, 954 Management of incontinence, 663, 667–668 Manganese tripeptide complex, 1113 Manifestation, 32, 45, 49, 50, 86, 88, 96, 129–137, 277, 300, 330, 465, 509, 530, 531, 547, 640, 641, 646, 829, 830, 846, 936, 938, 949–951, 1019–1022, 1024, 1143–1144, 1175 Mannose binding lectin (MBL), 254 Map of the human face, 173–181 Marital status, 444, 445 Marketing communication, 1193, 1194 Markets, 260, 735, 736, 799, 800, 866, 929, 940, 1063, 1082, 1083, 1124, 1150, 1151, 1156, 1187–1194, 1197–1199, 1201–1204 Matrix metalloproteinase‐1 (MMP–1), 38, 39, 90, 96, 103–105, 131, 205, 302, 316–318, 328, 329, 421–423, 429, 448, 449, 782, 901, 1080, 1111 Matrix-metalloproteinase‐9 (MMP–9), 80–82, 85, 87, 88, 90, 96, 104, 122–124, 329, 415, 429, 782, 901, 1111 Matrix metalloproteinases (MMPs), 30, 38, 40, 49–51, 80, 95, 103–104, 106, 121–127, 131, 227, 234, 283, 302, 316, 337, 415, 416, 420–422, 429, 430, 442, 443, 447–449, 554, 653, 782, 816, 901, 903, 939, 988, 991, 1021, 1057, 1067, 1073, 1111 Matrixyl, 1073 Mechanobiology, 47, 51, 266 Medium depth peels, 607, 1152, 1153, 1177 Melanin, 19, 40, 49, 135, 205, 281, 324, 395, 439, 495, 503, 509, 545, 567, 582, 716, 749, 781, 805, 937, 992, 1012, 1019, 1057, 1153 Melanocytes, 5, 19, 25, 37, 45, 93, 101, 131, 152, 193, 209, 281, 297, 326, 343, 366, 385–390, 395, 453, 471, 487, 495, 503, 509, 545, 573, 579, 610, 718, 801, 871, 897, 937, 983, 1014, 1019, 1115, 1147 Melanocyte-stimulating cytokine, 385–390 Melanogenesis, 152, 439, 495, 497, 505, 509–511, 515–516, 518, 576, 937, 1064 Melanoma, 112, 152, 205, 243, 329, 395, 439, 455, 545, 567, 579–585, 601, 609–614, 750, 759, 954 Melanoma acquisition, 609–611, 613, 614 Melanosome, 205, 326, 495, 497, 498, 503–507, 509–516, 716, 717, 937, 938, 1019 Melanosome transfer, 205, 498, 504, 510–515, 938 Melasma, 208, 209, 495, 497, 498, 516, 518, 937, 1022, 1023, 1153, 1154, 1156 Melatonin, 1090, 1109, 1110, 1113 Men, 6, 25, 135, 160, 173, 239, 260, 266, 344, 353, 366, 373, 442, 518, 527, 547, 579, 627, 668, 678, 697, 759, 793, 830, 849, 915, 937, 952, 960, 974, 983, 999, 1023, 1027, 1132, 1148 Menopausal hormone therapy (MHT), 361 Menopause, 25, 51, 97, 143, 237, 248, 253, 257, 343, 353, 361, 374, 444, 626, 679, 883–891, 915, 940, 983, 1013, 1127, 1177 Mesenchymal stem cell (MSC), 201, 202 Metabolic pathways, 308 Metabolism, 5, 25, 38, 51, 89, 94, 103, 137, 163, 213, 225, 248, 254, 277, 295–309, 313–318, 323, 350, 447, 609, 627, 642, 654, 695, 709, 773, 814, 827, 845, 930, 983, 1080, 1089, 1143 Metagenomic analysis, 871, 872 Microbiology, 871–880 Microbiota, 799, 811, 871, 883–891 Micro-circulation, 30, 159, 162, 174, 623, 624, 631, 632, 807, 826, 833, 836, 849, 898 Microdermabrasion, 1022, 1154–1155, 1200 Microflora skin alteration, 813–814 Micro-inflammation and aging, 789–794 Microorganisms, 343, 345, 382, 393, 394, 538, 643–645, 720, 800, 806, 811, 812, 817, 871, 875, 876, 878, 883, 888, 897 Microrelief lines, 717, 723 Microscopy, 14, 32, 39, 55, 60, 63, 67, 113, 117, 124, 125, 191, 225–227, 241, 244, 247, 296, 344, 404, 464, 474, 480, 504, 535, 537, 677, 679, 680, 683, 699, 700, 706, 707, 716–719, 737, 738, 741, 782, 789, 818, 1085 Microvascular aging, 13–17 Microvasculature, 13, 135, 163, 165, 283, 357, 833, 836, 1007–1009 Mid-volar forearm, 726, 731 Minimum erythema dose (MED), 206, 337, 506, 1066 Mitochondria, 39, 47, 101–103, 289, 295–306, 313–318, 323, 329, 422, 423, 453, 455, 488, 606, 802, 1200 Mitochondrial creatine kinase (mt-CK), 298, 299, 305 Mitochondrial DNA (mtDNA), 93, 96–97, 101, 289, 295, 313, 327, 422, 453, 611, 938 Mitochondrial DNA theory, 96–97 Mitochondrial permeability transition pores (MPTP), 301 MMP‐9 See Matrix-metalloproteinase‐9 Model of age, 467, 978 Modified Forearm Controlled Application (mFCAT), 840 Mohs micrographic surgery, 243, 601 MoistureMeter, 692 Moisturizers, 217, 378, 432, 498, 527, 648, 667, 668, 687, 688, 692, 742–745, 829, 933–935, 954, 1063, 1065, 1067, 1069, 1071, 1074, 1076, 1083, 1092, 1111, 1161, 1188, 1190– 1194 Molecular motion, 725, 729–731 Mouse skin, 6, 9, 11, 117, 152, 208, 214, 237, 439, 573, 575, 774, 775, 782 Mouse skin aging, 11 MRSA, 427, 875, 876, 879 mtDNA deletions, 301, 316, 317, 453, 455, 456 Murine models, 131, 413, 414, 418 Muscle contraction, 52, 259, 304, 911, 912, 914, 915, 1112 Mutations, 39, 47, 79, 93, 101, 116, 121, 129, 193, 300, 314, 323, 333, 429, 455, 461, 505, 513, 545, 567, 579, 587, 642, 781, 848, 929, 989, 1056 N Nail – dystrophy, 240–244 – histology, 240 – infection, 239–243 – melanoma, 243–244 – plate, 239–243 Narcissism, 950, 968 Nasolabial area (NL), 173–181, 697 National Institutes of Health (NIH), 260, 477 Natural killer T (NK-T) cells, 183, 188, 576 Natural moisturizing factors (NMF), 55, 64– 66, 69, 70, 371, 654, 659, 660, 706, 735–737, 739, 740, 742, 745, 931–934, 1023, 1065 Naturals/organics, 1201–1202 Neck, 28, 48, 121, 173–180, 316, 333, 357, 378– 380, 382, 453, 514, 535, 547, 549, 558, 567, 568, 602, 641, 645, 648, 681, 682, 697, 698, 749, 977, 1109, 1113, 1122, 1123, 1142, 1146, 1154, 1162, 1164, 1169, 1170, 1172, 1180, 1181 Necklift, 1181 Neocutis, 1081, 1083 Neoplasia, 88, 121, 132, 147, 152, 333, 455, 567, 587, 596, 877 Neovascularization, 106, 626, 904, 1144 Nerve growth factor (NGF) protein, 147–150, 152–156, 657, 826, 1082 Nerves, 7, 50, 135–136, 148, 165, 180, 286, 538, 619, 622–624, 632, 790, 791, 801, 1024, 1064, 1144, 1182 Neuropeptide regulation, sebum, 350 Neuropeptides, 350, 357, 622, 623, 640, 646, 790–792 Neurosensory, 30, 33, 34, 37 Neurotoxin, 1073, 1147, 1148, 1175, 1177 Neurotransmitter inhibitor peptides, 1090, 1112 Neurotrophin‐3 (NT‐3) protein, 147–149, 151–156 Neurotrophin‐4 (NT‐4) protein, 147, 148, 152 Neurotrophins (NTs), 147–156 Neutrophils, 254, 281, 395, 413, 430, 791, 899, 900, 1079 Subject Index N6-furfuryladenine (Kinetin), 490, 1074, 1109 Niacinamide, 324, 498, 499, 742, 744, 751, 936, 938, 1070–1072, 1076, 1077, 1109 Nitric oxide, 164, 165, 214, 299, 412, 496, 569, 619–624, 626–633, 817, 1059 Nitroxide spin probe or spin label, 726 NMF See Natural moisturizing factors Nonablative lasers, 1020, 1147, 1157–1161 Nonimmunologic contact urticaria, 178–179 Non-melanoma skin cancer, 152, 455, 456, 567, 568, 577, 587–596, 601, 614 Normal microbiota, 802, 814, 880, 883–888 Nose, 130, 173–180, 343, 380, 381, 535, 537, 538, 562, 604, 605, 681, 697, 752, 764, 879, 976, 977, 1177 NouriCel-MD, 1081–1083, 1085 Nova dermal phase meter, 692 Nuclear factor (kB), 95, 214, 413, 414, 515, 631 Nucleotide excision repair, 288, 324–325, 328, 329, 546, 570, 573, 577, 582 Nummular (Discoid) eczema, 527, 531–532, 641 N-undecylenoyl-phenylalanine, 498, 499 Nutraceuticals, 1199 Nutriceuticals, 490 Nutricosmetics, 1199 Nutrition, 132, 295, 304, 361, 364, 393, 487, 490, 507, 537, 539, 547, 619, 663, 667, 790, 804, 811, 814, 817, 877, 886, 939, 983, 988–989, 1014, 1058, 1081, 1131, 1197, 1199, 1200, 1204 O Occlusion, 29, 179, 349, 401, 402, 535, 625, 628–630, 633, 663–665, 689, 697, 721, 741, 742, 826, 829, 836, 837, 846, 851, 872, 988, 1067, 1131, 1151 Occlusives, 221, 434, 648, 687, 688, 737, 741, 826, 829, 837, 933–935, 1158 Occupational dermatology, 826, 828, 830 Ochronosis, 1020, 1021, 1064 Onychauxis, 240–242 Onychoclavus, 240, 242 Onychocryptosis, 240, 242–243 Onychogryphosis, 240, 242 Onychomycosis, 240–242, 1132 Onychophosis, 240, 242 Onychoschizia, 240 Opioid growth factor receptor (OGFr), 601 Order parameter, 728–732 Ordinal rating scale, 921 Osmolarity, 624, 628 Osteoporosis, 88, 102, 132, 239, 240, 302, 358, 365, 490, 782, 966, 976 Ovarian cycle, 349, 355 Oxidative damage, 8, 38, 102, 105, 225, 288, 289, 298–300, 302, 304, 306, 307, 314, 315, 317, 327, 413, 418, 420, 422, 443, 455, 461, 571, 591, 631, 815, 816, 875, 988, 992, 1072, 1074, 1080, 1109, 1113, 1147 Oxidative phosphorylation (OXPHOS), 101, 295–299, 302, 305, 314, 315, 455, 570 Oxidative phosphorylation efficiency, 297 Oxidative stress, 46–48, 93, 97, 103, 106, 201, 204, 205, 231, 285, 286, 288–289, 298, 301–303, 305, 306, 313–318, 357, 413–418, 420, 453, 455, 477–481, 484, 490, 589, 592, 622, 631, 812, 815–816, 938, 1059, 1109 Oxo-guanine glycosylase–1 (OGG1), 325, 326 Ozone (O3), 38, 39, 323, 411–421, 427, 429, 453, 568, 709, 783, 992 P p53, 47, 95, 129, 148, 288, 327–329, 423, 430, 515, 546, 547, 549, 554, 556, 570–575, 582, 589, 590, 939, 1056 P450, 289, 554, 850 Pal-KTTKS (palmitoyl pentapeptide–4), 1073, 1074, 1076, 1089, 1092 Palmitoyl tripeptide–3/5 (Syn1-Coll), 1090–1091 Palmitoyl VGVAPG, 1092 Palmoplantar skin, 179, 377, 687 Papillary fibroblast, 465–467 Parakeratosis, 213, 395, 396, 706, 708, 825, 1126, 1127 Paraneoplastic pemphigus, 536 Paronychia, 241, 243, 645 Pathogenesis, 13, 96, 101, 104, 105, 129–137, 160, 203, 214, 242, 243, 336, 416, 448, 558, 642–644, 655, 665, 709, 829, 876, 891, 936 Pathogenic organisms, 885, 887, 890 Pathogen inhibition, 871, 875–876 PCNA – in epidermis, 10 – in skin, PDGFR expression, 14, 17 Pelvic muscle, 259, 1121–1123 Pemphigus, 534, 954 Pemphigus vulgaris, 534–536 Pentapeptide–3 (Vialox1), 1091, 1112 Pentapeptide–18 (Leuphasyl1), 1112 PEP–1-rpS3 fusion protein, 1111 Peptamide–6 (FV APFP), 1091 Peptide, 183, 225, 229, 350, 396, 413, 511, 513, 515, 619, 644, 646, 649, 656, 711, 791, 792, 876, 936, 939, 1067, 1073, 1074, 1077, 1089–1114, 1199 Peptides and proteins characteristics, 1093–1097 Peptide search strategy, 1091 Peptidylarginine deiminase (PAD), 65, 709 Perceived age, 442–446, 497, 500, 752, 973–979 Perception, 25, 37, 136, 168, 266, 286, 351, 355, 497, 509, 529, 664, 687, 716, 749–753, 757, 934, 959, 973–980, 987, 1024, 1027–1046, 1051, 1081, 1142, 1187, 1197 Percutaneous absorption, 29, 31, 32, 130, 173, 181, 695, 696, 698, 700, 701, 776, 833–834, 842, 849, 934 Percutaneous penetration, 180, 695, 697, 698, 771–779, 849 Pericytes, 13–16, 202, 203 Pericyte-to-endothelial cell ratios (PC/EC), 13–17 Perimenopause, 257, 260, 353, 355–357, 887 Perineal dermatitis, 663, 665, 829–830, 851 Perioral area, 173, 174, 176, 178, 697, 1082 Perlecan, 79–83, 87, 88, 90, 109, 116 Permanent fillers, 1152 Permeability, 27, 29–31, 139, 140, 213, 279, 280, 301, 305, 373, 402, 527, 620, 623, 624, 629, 642, 649, 655, 663, 668, 695–696, 698, 700, 701, 719, 772–774, 776, 779, 792, 801, 814, 826, 833, 834, 836, 837, 842, 849, 851, 898, 931, 932, 987, 1027, 1089, 1111, 1113, 1114, 1127, 1128, 1130 Permeability barrier homeostasis, 139, 140, 280, 932 Permeation coefficients (Kp), 701, 1092 Peroxisome proliferator activated receptors (PPARs), 213–221, 285 Persistent wrinkles, 911, 912, 914–917 Personality disorder, 967, 968 Personal products, 771, 1036–1038, 1043, 1044 pH, 30, 38, 60, 139, 173, 236, 247, 255, 257, 284, 401, 505, 642, 663, 677, 708, 718, 735, 782, 802, 812, 826, 875, 883, 931, 987, 1003, 1065, 1071, 1089, 1128 Phaseshift rapid in vivo measurement of skin (PRIMOS), 1083, 1084 Phosphatidylinositol 3-kinase (PI3K), 132, 627, 628, 631 Photoaging, 19–21, 37, 47, 69, 90, 93, 101, 113, 121, 129, 147, 163, 176, 201, 265, 295, 315, 323, 333, 354, 403, 411, 431, 443, 447, 453, 463, 477, 573, 579, 609, 677, 708, 715, 758, 771, 781, 804, 812, 836, 897, 921, 934, 973, 983, 1019, 1047, 1056, 1065, 1113, 1154 Photoaging scale, 921, 1022 Photodamage, 32, 38, 47, 63, 104, 129, 147, 204, 216, 236, 328, 337, 343, 354, 429–439, 443, 448, 455, 504, 547, 607, 609, 678, 749, 782, 911, 921, 939, 950, 959, 989, 1019, 1079, 1090, 1152 Photodynamic therapy (PDT), 243, 423, 546, 548, 554, 596, 604, 606 Photometric method, 346 Photon emission detection, 477, 479 Photoproducts, 323, 324, 328, 430, 478, 509, 569, 570, 572, 573 Photoprotection, 41, 50, 325, 327–329, 423, 424, 437, 439, 464, 509, 804, 1019, 1059 Photoprotection of epidermis, 986 Photoreactivation, 325 Physical difference, 158 Physical exercise, 790, 792–793 Physical property, 62, 66, 69, 265, 375, 436, 480, 509, 776, 1019, 1156 Physicochemical regulation, sebum, 349 Physiological changes, 5, 30–33, 37, 51, 160, 163, 164, 170, 270–271, 282–286, 358, 668, 841, 845, 878, 973, 1027, 1065, 1134 1215 1216 Subject Index Physiology, 45, 51, 52, 77, 116, 118, 130, 228, 277, 281–286, 351, 353, 355, 358, 361, 374, 375, 412, 415, 418, 487, 488, 582, 592, 666, 700, 720, 779, 817, 833, 877, 880, 884, 911, 987, 1014, 1019, 1024, 1047–1048, 1126– 1134 Phytosterol, 496 Pigmentary disorders, 1022, 1023 Pigmentation, 29, 38, 86, 130, 147, 162, 209, 216, 236, 282, 326, 385, 429, 447, 453, 461, 495, 503–507, 509–519, 533, 561, 576, 583, 591, 602, 609, 641, 678, 717, 759, 784, 877, 897, 911, 921, 929, 951, 976, 984, 1012, 1019, 1057, 1067, 1083, 1109, 1153 Pilosebaceous follicles, 344, 357–358, 394 p75 kDa NT receptor (p75NTR), 147–149, 152 PLA cell, 202, 206, 208 Plasma glucose, 627, 657 Plasmin, 62, 67, 70, 123, 125–127, 337, 708 Platelets, 48, 105, 115, 328, 620, 898–900, 1059, 1079, 1082, 1156 PLS model, 978–979 Pollution, 316, 323, 412, 629, 677, 802, 812, 877, 939, 992, 1081 Poly-L-lactic acid (Sculptra1), 1151, 1152 Polymethylmethacrylate (PMMA), 1149, 1152 Polymorphous light eruption (PLE), 307, 430 Post-inflammatory hyperpigmentation (PIH), 209, 210, 495–497, 518, 937, 1019, 1020, 1022, 1024 Postmenopause, 25, 353, 358, 374, 886–891, 1013, 1127–1130, 1133, 1134 Post-occupational dermatitis, 828 Posttraumatic stress disorder (PTSD), 967 Potential DNA damage, 454 PPAR See Peroxisome proliferator activated receptors Prebiotics, 799–807, 812, 818 Pressure ulcers, 163, 164, 537, 663–667, 826, 829, 1132, 1133 Prevelance of incontinence, 663 Probiotics, 257, 649, 783, 799–807, 811–818, 880, 1119 Product design, 1124, 1186–1195 Products, 8, 17, 21, 25, 49, 69, 85, 105, 109, 123, 132, 139, 159, 178, 214, 227, 240, 247, 254, 259, 271, 281, 299, 329, 333, 345, 397, 412, 422, 429, 455, 468, 490, 496, 506, 529, 559, 575, 643, 653, 665, 705, 719, 735, 758, 779, 804, 811, 828, 837, 845, 857–867, 883, 922, 929, 983, 1028, 1051, 1058, 1063, 1070, 1080, 1089, 1121–1125, 1133, 1148, 1187– 1195, 1197 Product usage, 743, 851, 853, 935, 1124, 1194 Profilometric method, 130, 394 Profilometry, 9, 266, 679, 680 Progeria syndromes, 129, 441 Progeroid syndromes, 96, 101, 129 Proliferation, 6, 17, 25, 39, 51, 80, 93, 105, 115, 132, 147, 174, 192, 203, 213, 226, 243, 280, 313, 344, 358, 365, 371, 388, 415, 423, 434, 449, 487, 497, 510, 545, 572, 580, 587, 601, 621, 653, 667, 683, 722, 737, 801, 815, 826, 875, 901, 930, 991, 1056, 1066, 1069, 1079, 1090, 1132, 1201 Propionibacterium, 343, 802, 803, 814, 871, 877–879 Propionibacterium acnes, 872, 873, 879, 936 Propylene glycol, 259, 933–935, 937, 1065 Protease, 17, 50, 60, 62–64, 69, 70, 72, 123, 140, 232, 254, 280, 281, 365, 511, 642, 708, 744, 814, 903, 931, 938 Protease-activated receptor (PAR)–2 blockers, 938 Proteins, 6, 17, 25, 38, 49, 55, 77–90, 94, 101, 109, 131, 140, 147, 160, 181, 183, 192, 201, 213, 225, 239, 247, 254, 277, 296, 313, 324, 333, 355, 361, 371, 378, 390, 393, 401–406, 413, 422, 430, 441, 447, 453, 479, 488, 495, 504, 510, 534, 547, 570, 589, 609, 621, 642, 654, 695, 705, 736, 784, 790, 801, 814, 826, 849, 871, 898, 931, 988, 1023, 1055, 1066, 1069, 1079, 1089–1114 – extract, 206–211, 657 – oxidation, 101, 105, 106, 289, 300, 318, 413, 414, 416, 609, 611 – quantification, 401–406, 695 Proteoglycans, 49, 79, 90, 103, 109–118, 122, 135, 225, 226, 228, 231, 266, 267, 447, 448, 461, 470, 682, 1090, 1097 Proteomics, 203, 491, 495, 497, 1082 Pruritis ani and perianal inflammation, 667, 1132, 1134 Pruritus, 40, 51, 137, 344, 527, 529–531, 534, 602, 640, 641, 644, 648, 653, 663, 666, 687, 762, 764, 792, 829, 935, 949, 952, 1131, 1134, 1157, 1158, 1162 Pruritus ani, 663, 667, 759 Psoriasis, 213, 214, 244, 378, 395, 415, 418, 529, 531, 534, 568, 571, 591, 639, 659, 687, 707, 708, 710, 721–723, 762–765, 792, 801, 803, 807, 834, 877, 879, 950–955, 983, 1157 PSP, 1081–1085, 1110 Psychiatric, 86, 159, 665, 668, 950, 951, 954, 955, 960–965, 967, 968 Psychological, 136, 239, 277, 285, 480, 529, 605, 644, 646, 668, 669, 720, 757, 762, 763, 790, 792, 793, 949–955, 961–963, 967, 968, 994 Psychological factors, 646 Psychology of perception, 1186 Psychosocial, 354, 509, 539, 668, 949–955, 960, 962, 963, 965, 966 PTCH, 549, 571, 573 Pustular dermatitis, 828 PUVA, 556, 568, 571, 1110 Pyratine 6, 1074, 1075, 1091, 1093, 1098, 1109 Q Quality of life (QoL), 25, 34, 527, 538, 539, 563, 639–641, 669, 757–766, 793, 830, 921, 949, 952–955, 963, 1186 Quality of life Index for Atopic Dermatitis (QoLIAD), 764 Quantitative risk assessment (QRA), 847, 857, 859, 861–867 R Race, 175, 176, 380–381, 503, 619–633, 707, 974, 984, 988, 1024, 1142 Radical (free radical), 8, 38, 40, 46, 93–94, 129, 203–205, 225, 227, 231, 234, 236, 242, 286, 288, 289, 299, 301, 302, 305–307, 310, 314, 317, 411–413, 417, 418, 435, 437, 439, 443, 454, 455, 461, 477, 480–482, 569, 571, 576, 583, 591, 628, 629, 631, 726–729, 790, 801, 802, 805, 807, 815, 816, 875, 936, 1055– 1057, 1109 Radiotherapy, 604–606 Raman, 69, 378, 707, 718, 721, 723, 735–745 Raman spectroscopy, 377, 688, 721, 735–745 Rat skin, 7, 113, 114, 116, 775, 777, 784, 792 Rat skin aging, 8, 289, 784 Reactive oxygen species (ROS), 25, 37, 46, 93, 102, 203, 225, 288, 297, 324, 411, 422, 429, 443, 448, 453, 477, 538, 589, 789, 815, 936, 1055, 1067 Real-time chemiluminescent (RT-CL) detection, 481 Reconstructed skin – flexibility, 461–474 – production, 466, 468, 470–472 Reflectance or lightness (L*), 510, 512, 516 Regenerative capacity, 33, 202, 1081 Regulations, 3, 38, 66, 79, 97, 104, 113, 123, 132, 147, 166, 183, 191, 215, 227, 249, 281, 295, 317, 349, 357, 416, 423, 429, 443, 449, 490, 495, 504, 515, 545, 572, 581, 596, 601, 622, 646, 695, 708, 735, 758, 771, 782, 791, 801, 812, 826, 845, 879, 897, 989, 1057, 1064, 1079, 1155, 1200 Relaxed skin tension line, 267 Reliability, 20, 351, 356, 507, 759, 761–764, 1202 Reproducibility, 268, 345, 355, 681, 705, 762, 840, 921, 925–927 Resident biota, 871–872, 875–877 Resiquimod, 601–602 Response to insult, 215 Retail channels, 1188 Reticular fibroblast, 473 Retinoic acid (tretinoin), 104, 221, 230, 236, 350, 406, 461, 498, 680, 782, 934, 962, 966, 1066–1067, 1069, 1077, 1085, 1090, 1113 Retinoid, 216, 236, 350, 602, 782, 932, 938–940, 954, 1022, 1063, 1066–1067, 1069, 1070, 1153, 1154, 1161 Retinyl propionate (RP), 1069, 1070 RHAMM, 228–229, 235 Rheology, 265–272, 345, 349, 351, 358 Rhinoplasty, 962, 963, 968, 1181 Rhodamine 123 (R123), 303, 480 Rhytidectomy, 960, 968, 1172 Subject Index Rice protein/amino acids (Colhibin1), 1111 Risk assessment, 845–853, 857, 859, 861–867 Risk characterization, 847, 853, 857, 862, 863 Risk factors, 162–169, 353, 441, 532, 556, 558, 562, 571, 576, 579, 585, 588, 589, 609–614, 646, 663, 830, 879, 939, 966 Risk sub-population, 845 Rodent, 6–9, 114, 132, 773, 775, 781, 784 Rodent skin aging, 6–8 Rosacea, 537–538, 764–765, 790, 791, 935–937, 940, 954, 1154 Rosacea-Specific Quality of Life (RosaQoL), 764–765 S Safety evaluation, 477, 845–853, 857–867 Scale improvement, 927 Scale quality, 921–927 Scalpdex, 764 Scarring, 45, 64, 81, 83, 85, 86, 88, 89, 159, 161, 361, 365, 366, 538, 603, 606, 607, 762, 817, 1020, 1023, 1079, 1080, 1139, 1144, 1145, 1153, 1154, 1156, 1158–1162, 1165, 1170, 1177 Sebaceous gland, 5, 6, 8, 29, 133, 136, 140, 143, 151, 175, 178, 179, 187, 193, 266, 271, 277, 343–351, 357, 358, 414, 531, 534, 538, 573, 654, 655, 659, 677, 687, 718, 722, 739, 778, 801, 837, 871, 875, 898, 931, 932, 983, 985, 1013 Seborrhea, 343, 344, 346, 348, 350, 351, 358 Seborrheic dermatitis, 136, 137, 382, 395, 530, 534, 710, 877 Seborrheic keratoses (SKs), 396, 547, 801, 937, 1022, 1023, 1056, 1153 Sebufix, 346, 348, 349 Sebum, 26, 51, 59, 136, 140, 174, 343–351, 357, 361, 372, 379, 527, 609, 654, 677, 687, 722, 759, 801, 814, 860, 872, 930, 989, 999, 1070, 1109 Sebum casual level (CL), 348, 357, 999 Sebum-enriched reservoirs, 348 Sebumeter, 173, 346, 657, 677, 999 Sebum excretion and spreading, 345–348 Sebum excretion rate (SER), 348–351, 358, 678 Sebum production, 29, 51, 136, 142–143, 175, 177, 343–351, 357, 358, 677, 678, 872, 878, 932, 936, 989, 1070, 1109 Sebum replacement time, 348, 358 Sebum-sensitive tape techniques, 346–347 Sebutape, 346 SECMA 11, 1092 Secretory leukocyte protease inhibitor (SLPI), 254, 255 Selective estrogen receptor modulators (SERMs), 361, 365, 366 Self-consciousness, 962, 967 Self-esteem, 668, 949–951, 960–962 Semaphorin, 512, 513 Senescence, 9, 37, 45, 93, 113, 129, 266, 286, 300, 315, 327, 353, 441, 487, 516, 534, 582, 588, 631, 696, 783, 815, 903, 938, 1021, 1051, 1055, 1152 Senescenceaccelerated mouse (SAM), 300, 783 Senile changes in skin, Senile lentigo, 40, 547, 585 Senile xerosis, 65, 66, 68, 69, 72, 381, 653–656, 658, 687, 706 Sensitive population, 159–170 Sensitive skin, 396, 641, 663–669, 837, 859, 929, 935–938, 1027–1045 Sensory and pain, 33 Sensory irritation, 828, 1050 Sensory skin irritation, 1049–1050 S epidermidis, 343, 872, 875, 876, 878 Septic shock, 428 Serial Analysis of Gene Expression (SAGE (TM)), 129 Severity scale, 764, 921–927 Sexes, 6, 25, 179, 381, 442, 699, 988, 999, 1002, 1003, 1005, 1008, 1010, 1012, 1014 – characteristics, 999 – differences, 1003, 1008 – hormone influences, 372–374 – steroids, 97, 354, 355, 357, 983, 1056 Sexually-transmitted diseases, 254, 255 Shape of the face, 978, 1141 Shear stress, 619, 622, 623, 628 SIAscope, 750, 751 Siascopy, 500, 749, 750 Side population method, 194 Signal peptide, 1090–1113 Signal transduction, 40, 95, 115, 147, 228, 229, 236, 301, 307, 328, 416, 423, 449, 489, 495, 582, 594, 656, 657, 900, 939, 1109 Signature mutation, 323, 329, 567, 569–571, 588 Silk protein, 1111, 1112 Simulation, 298, 690, 691, 725, 729–732, 736, 851, 916–917 Singlet oxygen (1O2), 46, 102, 104, 302, 303, 327, 448, 453, 455, 477, 480–482, 548, 554, 569, 606 siRNA, 305, 512, 513 Skin, 5–11, 13–17, 19, 25–34, 37–42, 45–52, 55–72, 85–90, 93–98, 101–103, 105, 106, 109–118, 121–127, 129–137, 143, 144, 147–156, 162–168, 170 – aging, 5–11, 13–17, 19, 25–34, 37–42, 45–52, 55–72, 85–90, 93–98, 101–103, 105, 106, 109–118, 121–127, 129–137, 143, 144, 147–156, 162–168, 170 – aging assessment, 925 – allergies, 1031, 1034, 1043 – barrier, 64, 106, 142, 180, 181, 213, 230, 232, 250, 277–280, 284, 285, 288, 364, 377, 401, 413, 418, 506, 642–643, 645–648, 654, 677, 687, 695–697, 699, 701, 715, 718, 721, 723, 725, 735, 758, 801, 805, 807, 815, 817, 827, 833, 834, 845, 849, 872, 880, 932, 933, 937, 940, 1019, 1023, 1027, 1065, 1070, 1071, 1073, 1075 – benefit, 257–260, 1127–1134 – cancer, 37, 133, 152, 323, 366, 427, 430, 455, 503, 515, 546, 567, 579, 587–596, 601, 612, 677, 715, 759, 805, 984, 1057 – color, 49, 326, 330, 374, 495, 503–507, 509, 510, 515, 518, 678–679, 716, 717, 749, 751, 752, 937, 973, 977–980, 991, 1010–1012, 1109, 1189 – colour determinants, 1019 – differences, 49, 84, 718, 999, 1012, 1024 – diseases, 9, 30, 40–41, 129, 136–137, 144, 147, 214, 258, 378, 395, 398, 415, 418, 431, 527, 538, 626, 639, 640, 642, 647, 688, 722, 723, 759–763, 765, 766, 801 803, 814, 830, 859, 936, 949–952, 954, 955 – disorders, 8, 25, 87–88, 96, 153, 203, 214, 221, 527, 539, 711, 757–766, 781, 803, 804, 921, 949, 983, 1127–1134 – echogenicity, 681–683 – elasticity, 114, 363, 364, 366, 429, 430, 444, 699, 759, 801, 805, 912, 1002, 1003, 1021, 1047, 1080, 1092, 1111, 1153, 1164, 1165, 1170, 1177 – equivalent culture, 500 – histology, 5–6 – hydration, 26, 173, 176, 225, 227, 228, 230, 363, 529, 655, 660, 665, 721–723, 736, 737, 743, 815, 826, 849, 930–935, 988, 1002, 1003, 1063, 1128, 1132 – immunology, 253–256, 582 – impedance, 688, 689, 1112 – infections, 139, 140, 258, 285, 427, 529, 643, 645, 648, 878–880, 1154 – integrity, 81, 139, 140, 144, 506, 527, 531, 665, 668, 815, 864, 876–879, 983, 988, 1056, 1080 – integrity and cohesion, 139, 140, 144 – irritant reactivity, 986 – irritants, 32, 644–646, 833, 837–842 – irritation, 32, 179, 180, 398, 406, 698– 699, 827, 833–836, 839–842, 846, 847, 853, 1027, 1036–1038, 1043–1045, 1048– 1051, 1070, 1072, 1073, 1124, 1125, 1134 – lightening, 509, 1020 – lipid, 31, 439, 678, 721, 722, 725, 737 – metabolism, 249, 250, 281–282 – microbiota, 799, 802–803, 806, 807, 871–880 – moisture, 30, 51, 97, 225, 226, 230, 232, 361, 364, 537, 718, 721, 806, 1131, 1134 – morphology, 94, 318 – optics, 749 – pathology, 85, 87–89, 227, 277–289 – pH, 139, 140, 144, 173, 177–178, 250, 285, 642, 663, 677, 812, 814, 829 – physiology, 45, 116, 118, 228, 281–283, 412, 415, 877, 880 – pigmentation, 385, 503–507, 509, 510, 515, 678, 717, 937–938, 951, 984 1217 1218 Subject Index – reactivity, 173–181, 646, 1027, 1036, 1047–1051 – rejuvenation, 209, 421, 607, 784, 1021, 1022, 1079–1086 – sensitivity, 144, 180, 181, 668, 669, 840, 935–937, 1023, 1027–1031, 1035–1038, 1043–1045, 1047–1051, 1066 – sensitization, 836, 846, 853, 1050, 1063–1051 – structure, 25–27, 38, 97, 162, 288, 429, 503, 506–507, 632, 683, 716–720, 738, 740, 784, 800–802, 833, 873, 983, 989, 991, 992, 1019, 1021, 1047, 1170 – surface hydration, 378, 382, 655, 688, 690, 692, 826 – surface hydration state, 378, 688, 692 – surface roughness, 679–680, 1084 – surface topography grading, 19 – tags, 547 – temperature, 160, 162–164, 167, 168, 170, 173, 175–177, 351, 619, 623–625, 655, 700, 842, 988 – thickness, 27, 28, 39, 51, 97, 163, 271, 272, 358, 361–364, 371, 413, 439, 609–614, 680–682, 699, 723, 739, 773–775, 837, 845, 871, 912, 983, 984, 999, 1010, 1047, 1097, 1133, 1170, 1175, 1181 – transparency, 679 Skindex, 760–764, 952, 954 Skin-equivalent model, 123–127 SkinMedica, 1081, 1082 Skin surface biopsy (SSB), 705 SLC24A5, 506, 515 Sleep deprivation, 790, 793 Slow tumbling simulation, 725, 731 Small leucine-rich proteoglycans (SLRP), 109, 112–114 Smoking, 13, 48, 51, 52, 241, 316, 323, 363, 365, 441–444, 446–449, 537, 611, 622, 629, 631, 783, 802, 877, 886, 911, 916, 921, 939, 959, 973, 983, 988, 989, 992, 1021, 1081, 1142, 1147, 1165 Social skin, 949, 955 Sodium lauryl sulfate (SLS), 32, 33, 67, 68, 179–181, 496, 645, 668, 698, 699, 711, 732, 825–827, 833, 837, 838, 840, 842, 846, 937, 987, 988, 1005, 1007, 1027, 1048, 1129 Solar elastosis, 19, 40, 47, 49, 105, 209, 271, 333–339, 448, 558, 582–584, 789, 1081, 1139 Solar lentigines, 38, 40, 41, 48, 518, 519, 549, 581, 583, 612, 1153 Solar radiation, 25, 37, 49, 50, 363, 421, 439, 503, 545, 556, 558, 561, 610, 611, 722, 789 Solid organ transplant, 326, 575 Solutions, 139, 226, 343, 379, 397, 435, 500, 602, 736, 744, 784, 806, 1109, 1111, 1112, 1121–1125, 1182, 1189, 1198, 1200, 1205 Solvent water, 226 Somatosensory, 69 Soybean protein (Soja protein), 1111 Speckled perifollicular melanotic pattern (SPMP), 343 Spectroscopy, 233, 315, 377, 404, 437, 477, 480, 507, 688, 701, 718, 721–723, 725, 735–745 Sphingomyelinase, 140, 814, 815 Splinter hemorrhage, 240, 243 Squamous cell carcinoma (SCC), 40, 41, 132, 329, 415, 532, 536, 545, 547–549, 554–556, 558, 562, 567–571, 573–576, 579, 588, 590, 595, 601–607, 805, 954, 984 Squamous cell carcinoma in situ (SCCIS), 602, 604–607 Squamous metaplasia, 247, 255 Standardized reconstructed skin, 468 Staphylococcus aureus, 241, 427, 645, 648, 649, 872, 875, 876, 878–880 Stasis dermatitis, 532 Stem cell, 11, 112, 152, 191–197, 201–211, 226, 277, 385, 490, 516, 573, 626, 722, 782, 900, 1056, 1139, 1157, 1181, 1200 Stem cell factor (SCF), 152, 201–203, 385, 386, 390, 516 Stem cell niche, 191–193, 226 Steroids, 213, 237, 281, 350, 355, 377, 382, 531, 532, 535, 536, 648, 649, 695 Stinging response, 668, 937 Stool, 664, 665, 829 Stratum corneum (SC), 8, 19, 25, 40, 55–72, 116, 123, 130, 139, 153, 164, 173, 183, 193, 210, 250, 265, 277, 343, 357, 361, 371, 378– 382, 401–406, 413, 432, 447, 504, 516, 527, 568, 612, 640, 653, 677, 689, 695, 705, 715, 725–733, 735, 771, 790, 801, 811, 825, 833, 849, 911, 930, 985, 999, 1019, 1052, 1065, 1075, 1086, 1089, 1194 – cell layers, 84, 377–382, 687 – hydration, 173, 176, 179, 654, 655, 657, 735–745, 931 – thickness, 402, 695, 735, 736, 738–744 – turnover, 173, 174 Streptozotocin (STZ), 653–657, 659 Stress, 29, 46, 84, 93, 103, 135, 164, 188, 201, 226, 260, 267, 285, 295, 313–318, 328, 351, 373, 393, 411, 423, 453, 477, 490, 529, 562, 572, 582, 589, 611, 619, 644, 653, 697, 725, 790, 801, 812, 837, 845, 912, 923, 929, 952, 961, 973, 991, 1008, 1036, 1047, 1056, 1109, 1121, 1130 Stress-induced premature aging, 47, 48, 301, 357 Stress oxidative, 46, 47, 93, 103, 106, 201, 204, 205, 231, 285, 286, 288–290, 298, 301–303, 305, 306, 313–318, 357, 413–418, 420, 453, 455, 477–481, 484, 490, 589, 592, 622, 631, 812, 815–816, 938, 1057, 1059, 1109 Structural changes, 6, 13, 27–30, 34, 39–40, 49, 63, 116, 142–143, 166, 168, 356, 488, 632, 682, 683, 759, 833, 842, 1084 Structure, 25, 38, 45, 55, 77, 95, 104, 109, 121, 143, 156, 162, 173, 213, 225, 240, 247, 265, 277, 298, 313, 333, 344, 353, 371, 377, 393, 401, 411, 429, 447, 461, 500, 503, 510, 532, 549, 572, 579, 592, 632, 655, 663, 680, 687, 695, 706, 715, 725–733, 735, 773, 784, 800, 814, 826, 833, 845, 857, 873, 886, 899, 921, 938, 949, 983, 999, 1019, 1047, 1055, 1063, 1109, 1127, 1147, 1178 Subclinical melanoderma, 47, 266 Submentoplasty, 1180, 1181 Subtypes, 68, 204, 241, 298, 549, 571, 579, 640–642, 828, 829, 935, 936, 1112, 1148 Subungual hematoma, 240, 243 Sunburn, 32, 37, 40, 324, 325, 327, 411, 429, 431, 436, 464, 478, 496, 556, 558, 559, 567, 568, 573, 609–611, 613, 614, 715, 781, 805–806, 939, 989, 991, 1019, 1022, 1057, 1064, 1066, 1110 Sunburn alert, 1066 Sun damage, 225, 231, 236, 323–324, 443, 448, 495, 516, 530, 559, 567, 568, 571, 572, 576, 577, 583, 609, 681, 917, 991, 1190 Sun exposure, 16, 37, 38, 41, 52, 114, 132, 153, 208, 231, 236, 265, 270, 316, 323, 324, 329, 354, 364, 442–444, 446, 447, 453, 455, 461, 497, 498, 538, 547–549, 554, 558, 559, 561, 562, 567–569, 571, 576, 577, 580–583, 585, 609–611, 613–614, 681–683, 709, 759, 877, 897, 911, 912, 914, 921, 933, 940, 973, 989, 991, 992, 1012, 1020, 1021, 1056, 1063, 1064, 1081, 1142, 1153, 1158, 1172 Sunlight, 37, 41, 49, 51, 101, 121, 175, 231, 316, 323–324, 412, 421, 424, 429, 431, 436, 439, 495, 497, 558, 567–569, 571–573, 580, 581, 583, 587, 588, 678, 758, 781, 992, 1020, 1066 Sunlight exposure, 40, 333, 389, 497, 498, 504, 569, 572, 580, 609–614 Sunlight wavelengths, DNA damage, 323–324 Sun protection, 41, 284, 327, 421, 434, 480, 558, 559, 576, 610–611, 614, 682, 916, 933, 1019, 1022, 1083 Sun protection factor (SPF), 41, 434, 436, 444, 480, 498, 556, 559, 988, 1064, 1083 Sunscreen in childhood, 609–611, 613, 614 Sunscreens, 41, 90, 307, 424, 429, 443, 478, 498, 503, 548, 569, 595, 610, 759, 935, 954, 991, 1038, 1058, 1063, 1081, 1201 Superficial muscular aponeurotic system (SMAS), 130, 1147, 1169–1171, 1180, 1181 Superficial peels, 1022, 1152–1154 Superoxide anion radical (O2À), 299, 477, 480–482 Superoxide dismutase, 47, 204, 236, 287, 288, 306, 314, 327, 414, 417, 479, 709, 875, 1090, 1109, 1113 Surfactant, 179, 254, 393, 397, 398, 413, 434, 496, 725, 732, 837, 858, 1133 Surgery, 1123 Surgical rejuvenation, 1181 Susceptibility, 37, 38, 45, 139, 140, 144, 179, 255, 300, 328, 365, 403, 414, 506, 576, 593, Subject Index 625, 631, 633, 639, 643, 644, 648, 663, 665, 667–669, 793, 816, 826, 829, 833–842, 845–847, 849, 853, 930, 937, 1005, 1027, 1048, 1050, 1051, 1127–1128, 1130, 1131, 1133 Symbionts, 875 Symbiosis, 880 Symmetric and asymmetric stem cell division, 192 Syndecans, 109, 111, 114–116, 1097 Syn1-Tacks, 1096, 1101 Systemic agents, cancer, 603–604 Systemic effects, DNA damage, 328 Systemic lupus, 761 Systemic toxicity, 435, 648, 847–851, 867 Systemic treatment, 237, 596, 601, 649, 950 T Tandem repeat, 77–79, 82, 83 Tape stripping, 29, 58, 60–63, 68, 69, 140, 142, 181, 284, 285, 381, 401–405, 435, 688, 689, 695, 698–700, 705–707, 710, 721, 736, 737, 826, 836, 988 Target of rapamycin (TOR) pathway, 132 Tazarotene, 601, 602 Technology advances, 1188 Telomere hypothesis, 46, 94, 95 Telomeres, 37, 46, 47, 88, 93–95, 97, 129, 196, 286–289, 357, 589, 591, 609, 611, 938, 939, 1021, 1056, 1058, 1080 Telomere shortening and DNA damage, 129 Temporary biodegradable fillers, 1149–1151 Temporary wrinkles, 915–917 Testosterone, 31, 32, 130, 179, 349, 350, 355, 363, 372, 627, 698, 772, 776–779, 834, 849, 984, 988, 1012, 1129 Tetramethylrhodaminemethyl ester (TMRM), 303 TEWL See Transepidermal water loss Textural changes, 991, 1020, 1023, 1160 Texture of the face, 751, 976, 977, 979, 1182 TGFbeta See Transforming growth factor-b TGF-b expression, 14, 17, 112, 228, 1091, T414G mutation, 302, 455, 456 Therapeutic options, 559, 936, 954, 955 Thermal injury, 159–170, 534, 1160 Thermoregulation, 27, 31, 32, 134, 166–168, 277, 282, 284, 286, 619, 758, 897, 989, 1008, 1023, 1024 Threshold of Toxicological concern (TTC), 865–867 Tobacco smoking, 39, 41, 447–449, 570, 629, 783, 1175 Topical, 9, 31, 50, 104, 133, 137, 143, 203, 213, 231, 241, 250, 285, 304, 317, 349, 361, 381, 396, 401, 418, 424, 431, 474, 479, 500, 530, 548, 577, 595, 602, 643, 655, 668, 683, 688, 695, 723, 735, 782, 800, 814, 829, 837, 876, 929, 962, 1002, 1020, 1059, 1067, 1069, 1079–1086, 1089–1114, 1132, 1154, 1177, 1189, 1200 Topical adrenocortical steroids, 259 Topical therapy, cancer, 601–603 Topical treatment, 230, 271, 355, 405, 496, 499, 518, 538, 556, 562, 605, 647, 648, 784, 807, 940, 1074, 1075, 1085, 1156 Total lipid content of SC, 699, 835 Toxicokinetic, 848, 850–852 Transcellular route, 771 Transcription coupled repair (TCR), 325, 326, 570 Transdermal delivery, 209, 210, 773 Transdermal drug delivery, 701, 773, 779, 1113 Transepidermal water loss (TEWL), 29, 59, 173, 279, 377, 401, 413, 418, 506, 529, 642, 665, 689, 695–701, 707, 721, 732, 736, 825, 835, 845, 930, 986, 1002, 1023, 1065, 1071, 1097, 1129 Transforming growth factor-b (TGF-b), 14, 17, 80, 95, 112, 115, 203, 226–228, 232, 237, 328, 429, 449, 817, 900, 902, 1079–1081, 1085, 1090, 1091, 1110 Transforming growth factor-b1 (TGF-b1), 14, 15, 17, 131, 365, 423, 449, 902–904, 1079–1082, 1110 Transforming growth factor-beta signalling pathway, 95 Transforming growth factors a and b, 1110 Transglutaminase (TGases), 55, 61, 63, 69, 213, 279, 707, 709 Transient biota, 871, 872 Treatment-general measures, 647 Trends, 412, 427, 489, 679, 741, 1050, 1149, 1197–1205 Trichloroacetic acid (TCA), 607, 851, 1153, 1175, 1177Trichothiodystrophy (TTD), 325, 326 Tripeptide‐1 (glycyl-L-histadyl-L-lysine (GHK)), 1090 Tripeptide‐3 (Syn1-Ake), 1112 Tripeptide‐10 Citrulline (Decorinyl™), 1091 Triterpenoid, 1075 TrpV, 623–625, 628 Tumor evasion, 588, 592, 594, 595 Tumor progression, 80, 81, 576, 582 Twin set analysis, 441–444 Type IV collagen, 49, 83, 121, 122, 194, 415 Type VII collagen, 49, 122, 125, 126 Tyramide signal amplification (TSA) technique, 149–151, 154, 156 Tyrosinase, 205, 388, 389, 498, 500, 505, 510, 515, 575, 576, 781, 937, 938, 1111 Tyrosinase inhibitors, 498, 500, 938 Tyrosinase-relating protein (TRP1), 205, 505, 510 Tyrosine kinase receptor, 147, 516 U Ubiquinone, 231, 296, 306, 1075 Ultrasonography, 363, 677, 680, 681, 683, 717 Ultrasound, 39, 165, 202, 269, 270, 374, 533, 549, 629, 677, 680–683, 717, 1113 Ultraviolet, 5, 19, 37, 47, 93, 129, 147, 162, 173, 225, 239, 265, 277, 302, 317, 322, 333, 343, 354, 389, 393, 411, 421, 427, 429, 443, 477, 497, 503, 545, 579, 587, 612, 716, 763, 771, 781, 789, 812, 897, 912, 921, 931, 983, 1019, 1048, 1080, 1147, 1175 Ultraviolet (UV) effects, 418, 427, 989 Ultraviolet (UV) light, 13, 19, 38, 41, 47, 129, 147, 162, 215, 225, 231, 265, 271, 284, 287, 295, 307, 343, 347, 348, 393, 430, 434, 436, 439, 463, 477, 478, 503, 506, 515, 545, 588, 771, 782, 804, 805, 816, 984, 988–992, 1012, 1019, 1021, 1022, 1024, 1065, 1066, 1175 Ultraviolet light B (UVB), 37, 41, 48, 101, 104, 105, 123, 125, 152, 204–207, 215, 236, 316, 317, 323, 324, 327–329, 333–339, 354, 389, 390, 411, 417, 423, 429–433, 437, 448, 453, 454, 463, 464, 477–484, 496, 515, 516, 545, 547, 559, 567–575, 587–589, 592–596, 649, 760 Ultraviolet radiation (UVR), 5, 7, 37, 131, 239, 277, 315–317, 326, 328, 329, 390, 421, 453, 455, 456, 497, 503, 506, 515, 581, 583, 609, 612–614, 648, 781, 789, 790, 812, 931, 989, 990, 1147 Ultraweak photon emission (UPE), 304, 479, 480 Upper eyelid (UE), 173, 180, 547, 697, 959, 978, 1140–1142, 1165, 1166, 1177, 1178, 1180, 1181 Urinary incontinence, 537, 663, 665, 668, 669, 829, 859, 890, 1028, 1043, 1045, 1121–1125, 1131–1134 Urinary tract infection (UTI), 257, 259, 890, 1130 Urine, 233, 350, 575, 663–665, 668, 774, 776–778, 829, 851, 857–863, 867, 934, 1121–1125 UV-A irradiation, 302, 303, 305, 306, 315, 317, 422, 575, 709 UV exposure, 38, 101, 103, 104, 133, 162, 173, 215, 231, 236, 288, 316, 317, 325, 327, 328, 415, 427, 447, 456, 463, 464, 471, 477, 495, 497, 500, 516, 545, 546, 548, 558, 559, 562, 568, 572, 577, 581–583, 594, 596, 614, 677, 781, 805, 921, 983, 988–992, 1022, 1057, 1111 UV-induced ROS, 316, 477–484 UV irradiation, 37, 38, 48, 90, 96, 105, 114, 132, 152, 153, 213, 215, 231, 297, 299, 305, 306, 324, 372, 393, 422, 429, 430, 443, 448, 449, 480, 511, 549, 577, 725, 806, 826, 827, 937, 939, 1019, 1047, 1066 UV response, 328, 572 V Vaginal epithelium, 247, 250, 884, 886, 888, 987, 1128, 1130 Vaginal microbiota, 883–891 Vaginal pathogens, 247 Vaginal pH, 247–250, 255, 257, 884, 886–891, 987, 1128, 1130 Vaginal secretions, 247–250, 253, 254, 257–259, 829, 884, 987, 1128, 1130 1219 1220 Subject Index Variability, 45, 130, 166, 177, 179, 180, 196, 265, 267, 355, 356, 576, 612, 628, 631, 696, 722, 739, 758, 775, 845–853, 863, 921, 926, 973, 1014, 1019, 1048, 1057 Vascular aging, 14, 789 Vascular disorders, 25, 536–538 Vascular endothelial growth factor (VEGF), 13, 83, 105, 115, 280, 416, 622, 626, 1079, 1082 Vascular endothelial growth factor (VEGF) expressions, 14, 105, 416, 904 Vascularization, 30, 32, 101, 104–106, 173, 175, 179, 240, 299, 507, 845, 849 Vasoconstriction, 32, 164–167, 282, 286, 532, 619, 622–625, 627–629, 632, 790, 791, 1047 Vasodilatation, 164–167, 357, 619, 620, 622, 624, 627–632 V-CAM 1, 791 VEGF See Vascular endothelial growth factor Versican, 49, 109, 113, 114, 117, 333, 334, 356, 448 Vicious cycle, 102, 258, 314, 316–318, 591, 663 V–600 Syris imaging system, 258 Vimentin, 303, 470, 472 Viral infection, herpes zoster, 538 Viscoelastic creep, 268 Visible light lasers, 1157, 1158 Vitamin A, 47, 51, 236, 304, 461, 991, 998, 1069, 1070, 1077 Vitamin B3, 744, 938, 1070–1072, 1077 Vitamin C, 51, 234, 236, 304, 327, 414, 437,462, 538, 547, 683, 937–939, 988, 992, 1022, 1072, 1090, 1109, 1110, 1113 Vitamin D, 30, 51, 132, 163, 213, 236, 237, 343, 507, 515, 577, 614, 644, 758, 782, 784, 1023, 1024 Vitamin E, 231, 236, 304, 306, 327, 343, 413, 414, 417, 418, 437, 439, 448, 547, 932, 935, 992, 1059, 1154, 1190 Vitiligo, 509, 951, 952, 954, 1158 Volume loss, 1021–1023, 1139, 1141–1144, 1175–1177, 1179, 1181 Volume restoration, 1149, 1176, 1178–1182 Vulvar folliculitis, 663, 667, 759, 1132 Vulvar intertrigo, 1132 Vulvar irritation, 669, 1127, 1129–1133 Vulvar physiology, 1127–1134 Vulvar susceptibility, 837 W Water, 26, 55, 135, 140, 159, 173, 225, 239, 277, 299, 313, 327, 349, 357, 364, 371, 377, 393, 401, 413, 428, 432, 506, 527, 569, 624, 641, 654, 664, 678, 687, 695–701, 705, 715, 725, 735, 772, 791, 801, 811, 826, 834, 847, 865, 872, 883, 897, 930, 988, 1002, 1020, 1065, 1071, 1097, 1121, 1129, 1156, 1199 – changes, 143, 741 – content, 26, 29, 69, 71, 143, 285, 289, 356, 364, 371, 378, 381, 506, 527, 640, 654, 655, 687–691, 695, 697, 701, 706, 720–723, 725, 735, 736, 739, 741, 742, 744, 759, 801, 826, 931, 987, 1065 – content of stratum corneum (SC), 26, 29, 69, 71, 143, 378, 381, 654, 655, 687, 688, 690, 691, 697, 701, 720, 723, 735, 736, 741, 742, 744, 931, 1065 – of hydration, 225, 226, 230, 232, 237 Water-holding substance, 687 Water-soluble constituents, 141 Weibull curve fitting, 739, 741 Werner’s syndrome (WS), 96, 129, 230 Western blot analysis, 447 Wipes, 840, 1123, 1124, 1127–1134 Women, 6, 25, 51, 130, 143, 154, 162, 173, 237, 239, 254, 257, 271, 334, 350, 353, 361, 372, 442, 497, 504, 516, 527, 547, 567, 625, 663, 678, 699, 725, 751, 759, 825, 841, 846, 857, 876, 883, 912, 922, 929, 954, 960, 973, 983, 999, 1023, 1027, 1047, 1111, 1121, 1127– 1134, 1142, 1148, 1177, 1187, 1200 Women’s Health Initiative (WHI) studies, 260, 361, Worsening weather, 427, 428 Wound healing, 5, 11, 14, 33, 37, 45, 51, 85, 88, 115, 131, 136, 153, 195, 201, 203, 204, 209, 210, 214, 231, 232, 235, 236, 286, 328, 329, 357, 361, 365, 366, 415–417, 421, 453, 490, 496, 509, 537, 591, 627, 629, 653, 723, 758, 790, 801, 807, 845, 876, 879, 897–904, 987, 1023, 1047, 1056, 1073, 1075, 1079–1083, 1085, 1090, 1109, 1110, 1113, 1156 Wounds, 5, 14, 33, 37, 45, 83, 94, 115, 123, 131, 153, 163, 195, 201, 214, 226, 286, 328, 346, 357, 361, 371, 415, 421, 453, 490, 496, 509, 537, 550, 591, 625, 653, 665, 723, 758, 771, 783, 790, 801, 812, 845, 876, 897–904, 984, 1023, 1027, 1047, 1056, 1073, 1079, 1090, 1152 Wrinkle measurement, 130, 1083, 1084 Wrinkles, 8, 25, 37, 47, 97, 121, 130, 147, 201, 216, 232, 266, 282, 306, 317, 329, 333, 356, 364, 394, 429, 444, 447, 678, 749, 758, 782, 790, 801, 817, 911–917, 921, 929, 949, 959, 973, 984, 1021, 1056, 1065, 1069, 1079, 1089, 1142, 1147, 1176, 1187, 1199 Wrinkling, 5, 19, 50, 86, 130, 162, 206, 225, 271, 283, 357, 361, 374, 444, 447, 461, 528, 680, 759, 782, 812, 877, 897, 911–917, 922, 929, 976, 984, 1021, 1064, 1069, 1081, 1109, 1177 Wrinkling ability, 130 X Xeroderma pigmentosum (XP), 325, 326, 330, 471, 546, 548, 558, 570–572, 576, 577, 606 Xerosis, 29, 51, 65, 136, 354, 381, 393, 403, 527, 640, 653, 687, 699, 706, 759, 815, 829, 873, 930, 954, 1065 Y Yeast, 81, 95, 241, 250, 254, 255, 395, 482, 534, 644, 645, 665, 801, 802, 806, 813, 818, 872, 876–879, 1091, 1092, 1110 Young’s modulus, 268 Youthfulness, 949, 1162 Z Zeatin, 490, 1074, Zyderm1, 1149, 1150 Zyplast1, 1149, 1150 ... 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