349 Aging Skin Barrier
(19) Dale BA, Resing KA, Lonsdale-Eccles JD. Filaggrin: a keratin filament associated protein. Ann N Y
Acad Sci. 1985 455:330–342.
(20) Kalinin A, Marekov LN, Steinert PM. Assembly of the epidermal cornified cell envelope. J Cell Sci.
2001 114:3069–3070.
(21) Candi E, Oddi S, Terrinoni A, et al. Transglutaminase 5 cross-links loricrin, involucrin, and small
proline-rich proteins in vitro. J Biol Chem. 2001 276:35014–35023.
(22) Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol
Cell Biol. 2005 6:328–340.
(23) Marekov LN, Steinert PM. Ceramides are bound to structural proteins of the human foreskin epidermal
cornified cell envelope. J Biol Chem. 1998 273:17763–17770.
(24) Grove GL, Kligman AM. Age-associated changes in human epidermal cell renewal. J Gerontol.
1983 38:137–142.
(25) Leveque JL, Corcuff P de, Agache P. In vivo studies of the evolution of physical properties of the human
skin with age. Int J Dermatol. 1984 23:322–329.
(26) Marks R, Barton SP. The significance of the size and shape of corneocytes. In: Marks R, Plewig G, eds.
Stratum Corneum. New York, NY: Springer-Verlag 1983:161–170.
(27) Rougier A, Lotte C, Corcuff P, Maibach HI. Relationship between skin permeability and corneocyte size
according to anatomic site, age, and sex in man. J Soc Cosmet Chem. 1988 39:15–26.
(28) Plewig G, Scheuber E, Reuter B, Waidelich W. Thickness of corneocytes. In: Marks R, Plewig G, eds.
Stratum Corneum. New York, NY: Springer-Verlag 1983:171–174.
(29) Wertz PW, Madison KC, Downing DT. Covalently bound lipids of human stratum corneum. J Invest
Dermatol. 1989 92:109–111.
(30) Wertz PW, Swartzendruber DC, Kitko DJ, Madison KC, Downing DT. The role of the corneocyte lipid
envelopes in cohesion of the stratum corneum. J Invest Dermatol. 1989 93:169–172.
(31) Nachat R, Mechin MC, Takahara H, et al. Peptidylarginine deiminase isoforms 1–3 are expressed in the
epidermis and involved in the deimination of K1 and filaggrin. J Invest Dermatol. 2005 124:384–393.
(32) Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat
stratum corneum is controlled by the water activity of the environment. Dev Biol. 1986 115:84–92.
(33) Scott IR, Harding CR, Barrett JG. Histidine-rich protein of the keratohyalin granules. Source of the free
amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum. Biochim Biophys Acta.
1982 719:110–117.
(34) Rawlings AV, Matts PJ. Stratum corneum moisturization at the molecular level: an update in relation to
the dry skin cycle. J Invest Dermatol. 2005 124:1099–1110.
(35) Rawlings AV, Scott IR, Harding CR, Bowser PA. Stratum corneum moisturization at the molecular
level. J Invest Dermatol. 1994 103:731–741.
(36) Kamata Y, Taniguchi A, Yamamoto M, et al. Neutral cysteine protease bleomycin hydrolase is essential
for the breakdown of deiminated filaggrin into amino acids. J Biol Chem. 2009 284:12829–12836.
(37) Spier HW, Pascher G. Analytical and functional physiology of the skin surface. Hautarzt. 1956 7:55–60.
(38) Cler EJ, Fourtanier A. L’acide purrolidone caboxylique (PCA) et la peau. Int J Cosmet Sci. 1981 3:101–106.
(39) Marty JP. NMF and cosmetology of cutaneous hydration. Ann Dermatol Venereol. 2002 129:131–136.
(40) Harding CR, Aho S, Bosko CA. Filaggrin revisited. Int J Cosmet Sci. 2013 35:412–423.
(41) Jokura Y, Ishikawa S, Tokuda H, Imokawa G. Molecular analysis of elastic properties of the
stratum corneum by solid-state 13C-nuclear magnetic resonance spectroscopy. J Invest Dermatol.
1995 104:806–812.
(42) Nakagawa N, Sakai S, Matsumoto M, et al. Relationship between NMF (lactate and potassium) content and
the physical properties of the stratum corneum in healthy subjects. J Invest Dermatol. 2004 122:755–763.
(43) Yamamura T, Tezuka T. The water-holding capacity of the stratum corneum measured by 1H-NMR. J
Invest Dermatol. 1989 93:160–164.
350 JOURNAL OF COSMETIC SCIENCE
(44) Robinson MH, Wickett RR. Biochemical and bioengineering analysis of the skin’s natural moisturizing
factors. J Cosmet Sci. 2004 55:211–212.
(45) Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the stratum corneum in normal skin:
relationship to the anatomical location on the body, age, sex, and physical parameters. Arch Dermatol Res.
1999 291:555–559.
(46) Holleran WM, Takagi Y, Menon GK, et al. Permeability barrier requirements regulate epidermal beta-
glucocerebrosidase. J Lipid Res. 1994 35:905–912.
(47) Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR, Elias PM. Processing of epidermal
glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. J Clin
Invest. 1993 91:1656–1664.
(48) Mao-Qiang M, Feingold KR, Jain M, Elias PM. Extracellular processing of phospholipids is required for
permeability barrier homeostasis. J Lipid Res. 1995 36:1925–1935.
(49) Mao-Qiang M, Jain M, Feingold KR, Elias PM. Secretory phospholipase A2 activity is required for
permeability barrier homeostasis. J Invest Dermatol. 1996 106:57–63.
(50) Fluhr JW, Kao J, Jain M, et al. Generation of free fatty acids from phospholipids regulates stratum
corneum acidification and integrity. J Invest Dermatol. 2001 117:44–51.
(51) Delfino M, Procaccini EM, Illiano GMP, Milone A. X-linked ichthyosis: relation between cholesterol
sulphate, dehydroepiandrosterone sulphate, and patient’s age. Br J Dermatol. 1998 138:655–657.
(52) Elias PM, Williams ML, Maloney ME, et al. Stratum corneum lipids in disorders of cornification: steroid
sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked
ichthyosis. J Clin Invest. 1984 74:1414–1421.
(53) Zettersten E, Man MQ, Sato J, et al. Recessive X-linked ichthyosis: role of cholesterol-sulfate accumulation
in the barrier abnormality. J Invest Dermatol. 1998 111:784–790.
(54) Swartzendruber DC, Wertz PW, Kitko DJ, Madison KC, Downing DT. Molecular models of the
intercellular lipid lamellae in mammalian stratum corneum. J Invest Dermatol. 1989 92:251–257.
(55) Marks R. Measurement of biological ageing in human epidermis. Br J Dermatol. 1981 104:627–633.
(56) Grove GL, Lavker RM, Hoelzle E, Kligman AM. Use of non-intrusive tests to monitor age-associated
changes in human skin. J Soc Cosmet Chem. 1981 32:15–26.
(57) Plewig G. Regional differences of cell sizes in the human stratum corneum. II. Effects of sex and age. J
Invest Dermatol. 1970 54:19–23.
(58) Starr NJ, Johnson DJ, Wibawa J, et al. Age-related changes to human stratum corneum lipids detected using
time-of-flight secondary ion mass spectrometry following in vivo sampling. Anal Chem. 2016 88:4400–4408.
(59) Imokawa G, Abe A, Jin K, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis:
an etiologic factor in atopic dry skin? J Invest Dermatol. 1991 96:523–526.
(60) Rogers J, Harding C, Mayo A, Banks J, Rawlings A. Stratum corneum lipids: the effect of ageing and
the seasons. Arch Dermatol Res. 1996 288:765–770.
(61) Denda M, Koyama J, Hori J, et al. Age- and sex-dependent change in stratum corneum sphingolipids.
Arch Dermatol Res. 1993 285:415–417.
(62) Wohlrab J, Gabel A, Wolfram M, et al. Age- and diabetes-related changes in the free fatty acid
composition of the human stratum corneum. Skin Pharmacol Physiol. 2018 31:283–291.
(63) Fujiwara A, Morifuji M, Kitade M, et al. Age-related and seasonal changes in covalently bound ceramide
content in forearm stratum corneum of Japanese subjects: determination of molecular species of
ceramides. Arch Dermatol Res. 2018 310:729–735.
(64) Choe C, Schleusener J, Lademann J, Darvin ME. Age-related depth profiles of human stratum
corneum barrier-related molecular parameters by confocal Raman microscopy in vivo. Mech Ageing Dev.
2018 172:6–12.
(65) Nilsson GE. Measurement of water exchange through the skin. Med Biol Eng Comput. 1977 15:209–218.
(66) Berardesca E, Maibach HI. Transepidermal water loss and skin surface hydration in the non-invasive
assessment of stratum corneum function. Derm Beruf Umwelt. 1990 38:50–53.
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Extracted Text (may have errors)

349 Aging Skin Barrier
(19) Dale BA, Resing KA, Lonsdale-Eccles JD. Filaggrin: a keratin filament associated protein. Ann N Y
Acad Sci. 1985 455:330–342.
(20) Kalinin A, Marekov LN, Steinert PM. Assembly of the epidermal cornified cell envelope. J Cell Sci.
2001 114:3069–3070.
(21) Candi E, Oddi S, Terrinoni A, et al. Transglutaminase 5 cross-links loricrin, involucrin, and small
proline-rich proteins in vitro. J Biol Chem. 2001 276:35014–35023.
(22) Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol
Cell Biol. 2005 6:328–340.
(23) Marekov LN, Steinert PM. Ceramides are bound to structural proteins of the human foreskin epidermal
cornified cell envelope. J Biol Chem. 1998 273:17763–17770.
(24) Grove GL, Kligman AM. Age-associated changes in human epidermal cell renewal. J Gerontol.
1983 38:137–142.
(25) Leveque JL, Corcuff P de, Agache P. In vivo studies of the evolution of physical properties of the human
skin with age. Int J Dermatol. 1984 23:322–329.
(26) Marks R, Barton SP. The significance of the size and shape of corneocytes. In: Marks R, Plewig G, eds.
Stratum Corneum. New York, NY: Springer-Verlag 1983:161–170.
(27) Rougier A, Lotte C, Corcuff P, Maibach HI. Relationship between skin permeability and corneocyte size
according to anatomic site, age, and sex in man. J Soc Cosmet Chem. 1988 39:15–26.
(28) Plewig G, Scheuber E, Reuter B, Waidelich W. Thickness of corneocytes. In: Marks R, Plewig G, eds.
Stratum Corneum. New York, NY: Springer-Verlag 1983:171–174.
(29) Wertz PW, Madison KC, Downing DT. Covalently bound lipids of human stratum corneum. J Invest
Dermatol. 1989 92:109–111.
(30) Wertz PW, Swartzendruber DC, Kitko DJ, Madison KC, Downing DT. The role of the corneocyte lipid
envelopes in cohesion of the stratum corneum. J Invest Dermatol. 1989 93:169–172.
(31) Nachat R, Mechin MC, Takahara H, et al. Peptidylarginine deiminase isoforms 1–3 are expressed in the
epidermis and involved in the deimination of K1 and filaggrin. J Invest Dermatol. 2005 124:384–393.
(32) Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat
stratum corneum is controlled by the water activity of the environment. Dev Biol. 1986 115:84–92.
(33) Scott IR, Harding CR, Barrett JG. Histidine-rich protein of the keratohyalin granules. Source of the free
amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum. Biochim Biophys Acta.
1982 719:110–117.
(34) Rawlings AV, Matts PJ. Stratum corneum moisturization at the molecular level: an update in relation to
the dry skin cycle. J Invest Dermatol. 2005 124:1099–1110.
(35) Rawlings AV, Scott IR, Harding CR, Bowser PA. Stratum corneum moisturization at the molecular
level. J Invest Dermatol. 1994 103:731–741.
(36) Kamata Y, Taniguchi A, Yamamoto M, et al. Neutral cysteine protease bleomycin hydrolase is essential
for the breakdown of deiminated filaggrin into amino acids. J Biol Chem. 2009 284:12829–12836.
(37) Spier HW, Pascher G. Analytical and functional physiology of the skin surface. Hautarzt. 1956 7:55–60.
(38) Cler EJ, Fourtanier A. L’acide purrolidone caboxylique (PCA) et la peau. Int J Cosmet Sci. 1981 3:101–106.
(39) Marty JP. NMF and cosmetology of cutaneous hydration. Ann Dermatol Venereol. 2002 129:131–136.
(40) Harding CR, Aho S, Bosko CA. Filaggrin revisited. Int J Cosmet Sci. 2013 35:412–423.
(41) Jokura Y, Ishikawa S, Tokuda H, Imokawa G. Molecular analysis of elastic properties of the
stratum corneum by solid-state 13C-nuclear magnetic resonance spectroscopy. J Invest Dermatol.
1995 104:806–812.
(42) Nakagawa N, Sakai S, Matsumoto M, et al. Relationship between NMF (lactate and potassium) content and
the physical properties of the stratum corneum in healthy subjects. J Invest Dermatol. 2004 122:755–763.
(43) Yamamura T, Tezuka T. The water-holding capacity of the stratum corneum measured by 1H-NMR. J
Invest Dermatol. 1989 93:160–164.
350 JOURNAL OF COSMETIC SCIENCE
(44) Robinson MH, Wickett RR. Biochemical and bioengineering analysis of the skin’s natural moisturizing
factors. J Cosmet Sci. 2004 55:211–212.
(45) Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the stratum corneum in normal skin:
relationship to the anatomical location on the body, age, sex, and physical parameters. Arch Dermatol Res.
1999 291:555–559.
(46) Holleran WM, Takagi Y, Menon GK, et al. Permeability barrier requirements regulate epidermal beta-
glucocerebrosidase. J Lipid Res. 1994 35:905–912.
(47) Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR, Elias PM. Processing of epidermal
glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. J Clin
Invest. 1993 91:1656–1664.
(48) Mao-Qiang M, Feingold KR, Jain M, Elias PM. Extracellular processing of phospholipids is required for
permeability barrier homeostasis. J Lipid Res. 1995 36:1925–1935.
(49) Mao-Qiang M, Jain M, Feingold KR, Elias PM. Secretory phospholipase A2 activity is required for
permeability barrier homeostasis. J Invest Dermatol. 1996 106:57–63.
(50) Fluhr JW, Kao J, Jain M, et al. Generation of free fatty acids from phospholipids regulates stratum
corneum acidification and integrity. J Invest Dermatol. 2001 117:44–51.
(51) Delfino M, Procaccini EM, Illiano GMP, Milone A. X-linked ichthyosis: relation between cholesterol
sulphate, dehydroepiandrosterone sulphate, and patient’s age. Br J Dermatol. 1998 138:655–657.
(52) Elias PM, Williams ML, Maloney ME, et al. Stratum corneum lipids in disorders of cornification: steroid
sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked
ichthyosis. J Clin Invest. 1984 74:1414–1421.
(53) Zettersten E, Man MQ, Sato J, et al. Recessive X-linked ichthyosis: role of cholesterol-sulfate accumulation
in the barrier abnormality. J Invest Dermatol. 1998 111:784–790.
(54) Swartzendruber DC, Wertz PW, Kitko DJ, Madison KC, Downing DT. Molecular models of the
intercellular lipid lamellae in mammalian stratum corneum. J Invest Dermatol. 1989 92:251–257.
(55) Marks R. Measurement of biological ageing in human epidermis. Br J Dermatol. 1981 104:627–633.
(56) Grove GL, Lavker RM, Hoelzle E, Kligman AM. Use of non-intrusive tests to monitor age-associated
changes in human skin. J Soc Cosmet Chem. 1981 32:15–26.
(57) Plewig G. Regional differences of cell sizes in the human stratum corneum. II. Effects of sex and age. J
Invest Dermatol. 1970 54:19–23.
(58) Starr NJ, Johnson DJ, Wibawa J, et al. Age-related changes to human stratum corneum lipids detected using
time-of-flight secondary ion mass spectrometry following in vivo sampling. Anal Chem. 2016 88:4400–4408.
(59) Imokawa G, Abe A, Jin K, et al. Decreased level of ceramides in stratum corneum of atopic dermatitis:
an etiologic factor in atopic dry skin? J Invest Dermatol. 1991 96:523–526.
(60) Rogers J, Harding C, Mayo A, Banks J, Rawlings A. Stratum corneum lipids: the effect of ageing and
the seasons. Arch Dermatol Res. 1996 288:765–770.
(61) Denda M, Koyama J, Hori J, et al. Age- and sex-dependent change in stratum corneum sphingolipids.
Arch Dermatol Res. 1993 285:415–417.
(62) Wohlrab J, Gabel A, Wolfram M, et al. Age- and diabetes-related changes in the free fatty acid
composition of the human stratum corneum. Skin Pharmacol Physiol. 2018 31:283–291.
(63) Fujiwara A, Morifuji M, Kitade M, et al. Age-related and seasonal changes in covalently bound ceramide
content in forearm stratum corneum of Japanese subjects: determination of molecular species of
ceramides. Arch Dermatol Res. 2018 310:729–735.
(64) Choe C, Schleusener J, Lademann J, Darvin ME. Age-related depth profiles of human stratum
corneum barrier-related molecular parameters by confocal Raman microscopy in vivo. Mech Ageing Dev.
2018 172:6–12.
(65) Nilsson GE. Measurement of water exchange through the skin. Med Biol Eng Comput. 1977 15:209–218.
(66) Berardesca E, Maibach HI. Transepidermal water loss and skin surface hydration in the non-invasive
assessment of stratum corneum function. Derm Beruf Umwelt. 1990 38:50–53.

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