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Skin

Anjali Chuttani, Barbara A. Gilchrest

10.1002/cphy.cp110111

Source: Supplement 28: Handbook of Physiology, Aging

Originally published: 1995

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 In Vitro Studies
2 Intrinsic Aging
2.1 Clinical Features
2.2 Histopathology
3 Extrinsic Aging
3.1 Photoaging
3.2 Cigarette Smoking
4 Physiological Changes
4.1 Barrier Function
4.2 Immune Function
4.3 Inflammatory Response
4.4 Wound Healing
4.5 Vitamin D Production
5 Summary
Figure 1. Figure 1.

Schematic drawings of young, aged, and photoaged skin. With aging alone, the interface between the dermis and the epidermis becomes flatter due to loss of the rete ridges. There is also a loss of Langerhans cells (suprabasilar dendritic cells) and melanocytes (dendritic pigment‐producing cells) in basal layer and reductions in dermal thickness, vascularity, and subcutaneous fat. In photoaged skin there is variable epidermal atrophy and hyperplasia, a further reduction in Langerhans cells, and an increase in melanocytes compared to age‐matched sun‐protected skin. Vessels in the superficial dermis are dilated, and there is a striking change in the quality of the dermal elastic tissue that is termed “elastosis.” Overall, aging alone results in skin that is less cellular and relatively atrophic, while photoaged skin may display either compensatory hypertrophy or further atrophy, depending on the severity of the cumulative UV injury.

Modified from Gilchrest 48 with permission


Figure 1.

Schematic drawings of young, aged, and photoaged skin. With aging alone, the interface between the dermis and the epidermis becomes flatter due to loss of the rete ridges. There is also a loss of Langerhans cells (suprabasilar dendritic cells) and melanocytes (dendritic pigment‐producing cells) in basal layer and reductions in dermal thickness, vascularity, and subcutaneous fat. In photoaged skin there is variable epidermal atrophy and hyperplasia, a further reduction in Langerhans cells, and an increase in melanocytes compared to age‐matched sun‐protected skin. Vessels in the superficial dermis are dilated, and there is a striking change in the quality of the dermal elastic tissue that is termed “elastosis.” Overall, aging alone results in skin that is less cellular and relatively atrophic, while photoaged skin may display either compensatory hypertrophy or further atrophy, depending on the severity of the cumulative UV injury.

Modified from Gilchrest 48 with permission
References
 1. Ammann, A. J., G. Schiffman, and R. Austrian. The antibody responses to pneumococcal capsular polysaccharides in aged individuals. Proc. Soc. Exp. Biol. Med. 164: 312–317, 1980.
 2. Andrew, W., R. H. Behnke, and T. Sato. Changes with advancing age in the cell population of the human dermis. Gerontologia 10: 1–19, 1964.
 3. Auerbach, H. Geographic variation in incidence of skin cancer in the United States. Public Health Rep. 7: 143–171, 1982.
 4. Azizkham, R. B., J. C. Azizkham, and B. R. Zetter. Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J. Exp. Med. 152: 931–944, 1980.
 5. Bailey, A. J., S. P. Robins, and G. Balian. Biological significance of the intermolecular crosslinks of collagen. Nature 251: 105–109, 1974.
 6. Baker, H., and C. P. Blair. Cell replacement in the human stratum corneum. Br. J. Dermatol. 80: 367–372, 1968.
 7. Barbee, R. A. Immediate skin test reactivity in a general population sample. Ann. Intern. Med. 84: 129–133, 1976.
 8. Barman, J. M., V. Percoraro, and I. Astore. Biological bases of the inception and evolution of baldness. J. Gerontol. 24: 163–170, 1969.
 9. Beauregard, S., and B. A. Gilchrest. A survey of skin problems and skin care regimens in the elderly. Arch. Dermatol. 123: 1638–1643, 1987.
 10. Becker, M. J., R. Farko, and M. Schneider. Cell mediated cytotoxicity in humans: age related decline as measured by xenography assay. Clin. Immunol. Immunopathol. 14: 204–210, 1979.
 11. Bentley, J. P. Aging of collagen. J. Invest. Dermatol. 73: 80–83, 1979.
 12. Besdine, R. W., Geriatric medicine: an overview. In: Annual Review of Gerontology and Geriatrics, edited by C. Eisdorfer. New York: Springer, 1979, p. 135.
 13. Bhawan, J., C. Oh, R. Lew, K. Nehal, R. Labadie, A. Tsay, and B. A. Gilchrest. Histopathological differences in the photoaging process in facial versus arm skin. Am. J. Dermatopathol. 14: 224–230, 1992.
 14. Bianco, C., and V. Nussenzweig. Complement receptors. Contemp. Top. Mol. Immunol. 6: 145–176, 1977.
 15. Black, M. M. A modified radiographic method for measuring skin thickness. Br. J. Derm. 72: 67–76, 1969.
 16. Braverman, I. M., and E. Fonferko. Studies in cutaneous aging: I. The elastic fiber network. J. Invest. Dermatol. 78: 434–443, 1982a.
 17. Braverman, I. M., and E. Fonferko. Studies in cutaneous aging II. The microvasculature. J. Invest. Dermatol. 78: 444–448, 1982b.
 18. Bullough, W. S., and E. B. Lawrence. Chalones and cancer. Nature 220: 134–135, 1968.
 19. Burke, B. L., R. W. Steel, and O. W. Beard. Immune responsiveness to varicellazoster in the aged. Arch. Intern. Med. 142: 291–293, 1982.
 20. Burley‐Rosset, M., and I. Jergnon. Interleukin‐1 synthesis and activity in aged mice. Mech. Ageing Dev. 24: 247–264, 1984.
 21. Carlizza, L., and E. Bologna. Variagioni della reativata cutana in rapporto con leta. Bull. Soc. Ital. Biol. Sper. 41: 344–348, 1965.
 22. Cauna, N., The effects of aging on the receptor organs of the human dermis. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 63.
 23. Cawley, E. P., Y. T. Hsu, and B. C. Sturgill. Lipofuscin (“wear and tear pigment”) in human sweat glands. J. Invest. Dermatol. 61: 105–107, 1973.
 24. Christophers, E., and A. M. Kligman. Percutaneous absorption in aged skin. In: Advances in the Biology of the Skin. edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. II, p. 163–175.
 25. Chu, A. C., J. A. K. Patterson, and G. Goldstein. Thymopoetin‐like substance in human skin. J. Invest. Dermatol. 81: 194–197, 1983.
 26. Cicerone, R. J. Changes in stratopheric ozone. Science 237: 35–42, 1987.
 27. Clark, R. A. F. Cutaneous tissue repair: basic biological considerations. Part 1. J. Am. Acad. Dermatol. 13: 701–725, 1985.
 28. Delo, V. A., L. Dawes, and R. Jackson. Density of Langerhans cells (LC) in normal vs. chronic actinically damaged skin (CADS) of humans. J. Invest. Dermatol. 76: 330–334, 1981.
 29. Dunouy, P., and A. Carrell. Cicatrization of wounds. J. Exp. Biol. 34: 339–348, 1921.
 30. Eaglstein, W. H., Wound healing and aging. In: Clinics in Geriatric Medicine, edited by B. A. Gilchrest. Philadelphia: W. B. Saunders, 1989, p. 183–187.
 31. Edick, G. F., and A. J. T. Millis. Fibronectin distribution on the surfaces of young and old human fibroblasts. Mech. Ageing Dev. 27: 249–256, 1984.
 32. Engel, A., M. L. Johnson, and S. G. Haynes. Health effects of sunlight exposure in the United States. Arch. Dermatol. 124: 72–79, 1988.
 33. Epstein, J. H. Photocarcinogenesis, skin cancer, and aging. J. Am. Acad. Dermatol. 9: 487–502, 1983.
 34. Epstein, J. H., and W. L. Epstein. A study of tumor types produced by ultraviolet light in hairless and hairy mice. J. Invest. Dermatol. 41: 463–473, 1963.
 35. Epstein, J. H., K. Fukuyama, and W. L. Epstein. UVL‐induced stimulation of DNA synthesis in hairless mice epidermis. J. Invest. Dermatol. 51: 445–451, 1968.
 36. Erschler, W. G. The influence of an aging immune system on cancer incidence and progression. J. Gerontol. 48: B3–B7, 1993.
 37. Fenske, N. A., and C. W. Lober. Structural and functional changes of normal aging skin. J. Am. Acad. Dermatol. 15: 571–585, 1986.
 38. Fleischmajer, R. Human dermal glycosaminoglycans and aging. Biochim. Biophys. Acta 279: 265–275, 1972.
 39. Forscher, B. K., and H. C. Cecil. Some effects of age on the biochemistry of acute inflammation. Gerontologia 2: 174–182, 1958.
 40. Frances, C., and L. Robert. Elastin and elastic fibers in normal and pathologic skin. Int. J. Dermatol. 23: 166–179, 1984.
 41. Garmyn, M., M. Yaar, N. Boileau, C. Backendorf, and B. A. Gilchrest. Effect of aging and habitual sun exposure on the genetic response of cultured human keratinocytes to solar‐simulated irradiation. J. Invest. Dermatol. 99: 743–748, 1992.
 42. Giacometti, L., The anatomy of the human scalp. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 97–104.
 43. Gilchrest, B. A. Age associated changes in the skin. J. Geriat. Soc. 30: 139–143, 1982.
 44. Gilchrest, B. A. In vitro assessment of keratinocyte aging. J. Invest. Dermatol. 81: 184s–189s, 1983.
 45. Gilchrest, B. A. Skin and Aging Process. Boca Raton, FL: CRC Press, 1984, p. 124.
 46. Gilchrest, B. A. Aging, J. Am. Acad. Dermatol. 11: 995–997, 1984.
 47. Gilchrest, B. A. In vitro studies of aging human epidermis. Rev. Biol. Res. Aging. 4: 281–289, 1990.
 48. Gilchrest, B. A., Physiology and pathophysiology of aging skin. In: Physiology, Biochemistry and Molecular Biology of the Skin (2nd ed.), edited by L. Goldsmith. New York: Oxford University Press, 1991, p. 1425–1442.
 49. Gilchrest, B. A. The variable face of photoaging: influence of skin type. Cosmetics Toiletries 107: 41–42, 1992.
 50. Gilchrest, B. A., and P. S. Friedmann. A culture system for the study of human melanocyte physiology. In: Structure and Function of Melanin, edited by K. Jimbow. Sapparo, Japan: Fujishoin 1986, vol. 4, p. 1–13.
 51. Gilchrest, B. A., and M. Yaar. Ageing and photoageing of the skin: observations at the cellular and molecular level. Br. J. Dermatol. 127 (suppl. 41: 25–30, 1992.
 52. Gilchrest, B. A., F. B. Blog, and G. Szabo. Effects of aging and chronic sun exposure on melanocytes in human skin. J. Invest. Dermatol. 73: 141–143, 1979.
 53. Gilchrest, B. A., G. Murphy, and N. A. Soter. Effect of chronological aging and ultraviolet irradiation on Langerhans cells in the human epidermis. J. Invest. Dermatol. 79: 85–88, 1982.
 54. Gilchrest, B. A., J. S. Stoff, and N. A. Soter. Chronologic aging alters the response to UV‐induced inflammation in human skin. J. Invest. Dermatol. 79: 11–15, 1982.
 55. Gilchrest, B. A., G. Szabo, E. Flynn, and R. M. Goldwyn. Chronologic and actinically induced aging in human facial skin. J. Invest. Dermatol. 80: 81s–85s, 1983.
 56. Gilchrest, B. A., M. A. Vrabel, E. S. Flynn, and G. Szabo. Selective cultivation of human melanocytes from newborn and adult epidermis. J. Invest. Dermatol. 83: 370–376, 1984.
 57. Gilman, S. C. Lymphokines in immunologic aging. Lymphokine Res. 3: 119–123, 1984.
 58. Girard, J. P., M. Paychere, and M. Cuevas. Cell mediated immunity in an aging population. Clin. Exp. Immunol. 27: 85–91, 1977.
 59. Glass, A. G., and R. N. Hoover. The emerging epidemic of melanoma and squamous cell cancer. JAMA 262: 2097–2100, 1989.
 60. Goldstein, S. Replicative senescence: the human fibroblast comes of age. Science 249: 1129–1133, 1990.
 61. Goodman, S. A., and T. Makinodan. Effect of age on cell mediated immunity in long lived mice. Clin. Exp. Immunol. 19: 533–542, 1975.
 62. Gottesman, S. R. S., R. L. Walford, and G. J. Thornbecke. Proliferation and cytotoxic immune functions in aging mice: II. Decreased generation of specific suppressor cells in alloreactive cultures. J. Immunol. 133: 1782–1787, 1984.
 63. Graham, J. A., and A. M. Kligman. Physical attractiveness, cosmetic use, and self‐perception in the elderly. Int. J. Cosmetic Sci. 7: 85–98, 1985.
 64. Greenberg, L. J., and E. J. Yunis. Immunological control of aging: a possible primary event. Gerontologica 18: 247–266, 1977.
 65. Grove, G. L. Age related differences in healing of superficial skin wounds in humans. Arch. Dermatol. 272: 381–385, 1982.
 66. Grove, G., Age associated changes in the replacement rates of exfoliated corneocytes in normal human skin. In: Cutaneous Aging, edited by A. M. Kligman and Y. Takase. Tokyo: University of Tokyo Press, 1988, p. 185.
 67. Grove, G. L., and A. M. Kligman. Age associated changes in human epidermal cell renewal. J. Gerontol. 38: 137–142, 1983.
 68. Grove, G. L., S. Duncan, and A. M. Kligman. Effect of aging on the blistering of human skin with ammonium hydroxide. Br. J. Dermatol. 107: 393–400, 1982.
 69. Grove, G. L., R. M. Lavker, E. Hoelzle, and A. M. Kligman. Use of noninvasive tests to monitor age associated changes in human skin. J. Soc. Cosmetic Chem. 32: 15–26, 1981.
 70. Hallgren, H. M., C. E. Buckley, and V. A. Gilbertson. Lymphocyte phytohemagglutinin responsiveness, immunoglobulins, and autoantibodies in aging humans. J. Immunol. 111: 1101–1111, 1973.
 71. Hallgren, H. M., J. H. Versey, L. J. Greenberg, and E. J. Yunis. T and B cells in aging humans. Federation Proc. 33: 646–647, 1981.
 72. Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37: 614–636, 1965.
 73. Hayflick, L., and P. S. Moorhead. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25: 585–621, 1961.
 74. Hill, W. R., and H. Montgomery. Regional changes and changes caused by age in normal skin. J. Invest. Dermatol. 3: 321–345, 1940.
 75. Hirokowa, K., Aging and the immune system. In: Cutaneous Aging, edited by A. M. Kligman and Y. Takase. Tokyo: University of Tokyo Press, 1988, p. 69.
 76. Holick, M. F., and J. MacLaughlin. Aging decreases the capacity of human skin to produce vitamin D3. J. Clin. Invest. 76: 1536–1538, 1985.
 77. Holick, M. F., J. A. MacLaughlin, M. B. Clark, J. T. Potts, R. R. Anderson, I. H. Blank, and J. A. Parrish. Photosynthesis of previtamin D3 in human skin and the physiological consequences. Science 210: 203–205, 1980.
 78. Holick, M. F., J. A. MacLaughlin, and S. H. Doppelt. Regulation of cutaneous previtamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science 211: 501–503, 1981.
 79. Holmes, F. F., J. Wilson, K. S. Blesch, P. R. Kaesberg, R. Miller, and R. Sprott. Biology of cancer and aging. Cancer 68: 2525–2526, 1991.
 80. Holm‐Pederson, P., and B. Zederfeldt. Granulation tissue formation in subcutaneously implanted cellulose sponges in young and old rats. Scand. J. Plast. Reconstr. Surg. 5: 13–16, 1971.
 81. Holm‐Pederson, P., and B. Zederfeldt. Respiratory gas tensions and blood flow in young and old rats. Scand. J. Plast. Reconstr. Surg. 7: 91–96, 1973.
 82. Holm‐Pederson, P., A. M. Fenstad, and L. E. A. Folke. DNA, RNA, and protein synthesis in healing wounds in young and old mice. Mech. Ageing Dev. 3: 173–185, 1974.
 83. Hurley, J. H., and W. B. Shelley. The Apocrine Sweat Gland in Health and Disease. Springfield, IL: Charles C Thomas, 1960.
 84. Ippen, M., and H. Ippen. Approaches to a prophylaxis of skin aging. J. Soc. Cosmetic Chem. 16: 305–308, 1965.
 85. Jacobson, E., J. Billings, R. Frantz, C. Kinney, M. Stewart, and D. Downing. Age related changes in sebaceous wax ester secretion rates in men and women. J. Invest. Dermatol. 85: 483–485, 1985.
 86. Joffe, I. Cigarette smoking and facial wrinkling. Ann. Intern Med. 115: 659, 1991.
 87. Johnson, M. L. T., and J. Roberts. Prevalence of Dermatological Disease among Persons 1–74 Years of Age: United States Advanced Data No. 4. Washington: USDHEW, 1977.
 88. Jones, P. G., C. A. Kaufman, and A. G. Bergman. Fever in the elderly: production of leukocyte pyrogen by monocytes from elderly persons. Gerontology 30: 182–187, 1984.
 89. Jung, E. G., and E. Bohnert. Lichtbiologie der Haut. In: Jadassohn, Handbuch der Haut‐und Beschlechtskrankheiten, Voli/4. Berlin: Springer, 1979.
 90. Kadence, D. P., R. Burr, R. Gress, R. Kanner, J. Lyon, and J. Zone. Cigarette smoking: a significant risk factor for premature facial wrinkling. Ann. Intern. Med. 114: 840–844, 1991.
 91. Kaplan, M. M., P. Gordon, C. Pan, J. Less, and B. A. Gilchrest. Keratinocytes convert thyroxine to triiodothyronine. Ann. N. Y. Acad. Sci. 548: 56–65, 1988.
 92. Kato, K., S. I. Keyama, and M. Takowki. Epithelial cell components: immunoreactants with antiserum thymic factor (FTS): possible association with intermediate filaments. Cell 24: 885–895, 1981.
 93. Kawamoto, T., M. Nishi, K. Takahashi, T. Nishiyama, J. D. Sato, and S. Taniyuchi. Stimulation by transforming growth factor‐beta of epidermal growth factor‐dependent growth of aged fibroblasts: recovery of high affinity ECF receptors and growth stimulation by EGF. In Vitro Cell Dev. Biol. 25: 965–970, 1989.
 94. Kligman, A. M. Early destructive effects of sunlight on human skin. JAMA 210: 2377–2380, 1969.
 95. Kligman, A. M. Perspectives and problems in cutaneous gerontology. J. Invest. Dermatol. 73: 39–46, 1979.
 96. Kligman, A. M., and A. K. Balin. Aging of human skin. In: Aging and the Skin, edited by A. K. Balin and A. M. Kligman. New York: Raven Press, 1989, p. 1–19.
 97. Kligman, A. M., G. L. Grove, and A. K. Balin. Aging of human skin. In: Handbook of the Biology of Aging, edited by C. E. Finch and E. L. Schneider. New York: Van Nostrand Rein‐hold p. 820–841, 1985.
 98. Kligman, L. H., Photoaging: manifestations, prevention and treatment. In: Clinics in Geriatric Dermatology, edited by B. A. Gilchrest. Philadelphia: WB Saunders, 1989 vol. 5, p. 235–251.
 99. Kligman, L. H. The ultraviolet‐irradiated hairless mouse: a model for photoaging. J. Am. Acad. Dermatol. 21: 623–631, 1989.
 100. Kligman, L. H., F. J. Akin, and A. M. Kligman. The contributions of UVA and UVB to connective tissue damage in hairless mice. J. Invest. Dermatol. 84: 272–276, 1985.
 101. Lavker, R. M. Structural alterations in exposed and unexposed skin. J. Invest. Dermatol. 73: 59–66, 1979.
 102. Lavker, R. M., and A. M. Kligman. Chronic heliodermatitis: a morphologic evaluation of chronic actinic damage with emphasis on the role of mast cells. J. Invest. Dermatol. 90: 325, 1988.
 103. Lavker, R. M., and T. T. Sun. Heterogeneity in epidermal basal keratinocyte morphological and functional correlations. Science 215: 1239–1241, 1982.
 104. Lavker, R. M., P. Zheng, and G. F. Dong. Aged skin: a study by light, transmission electron, and scanning electron microscopy. J. Invest. Dermatol. 88: 44s–51s, 1987.
 105. Lavker, R. M., P. Zheng, and G. F. Dong. Morphology of aged skin. In: Geriatric Derm, edited by B. A. Gilchrest. Philadelphia: WB Saunders, 1989, p. 53.
 106. Levin, M. J., M. Murray, H. A. Rotbart, G. O. Zerbe, C. J. White, and A. R. Hayward. Immune response of elderly individuals to a live attenuated varicella vaccine. J. Infect. Dis. 166: 253–259, 1992.
 107. Lewis, V. M., J. J. Twomey, and P. Bealmear. Age thymic involution and circulatory thymic hormone activity. J. Clin. Metab. 47: 145, 1978.
 108. Liu, J. J., M. Segre, and D. Segre. Changes in suppressor, helper and B cell function in aging mice. Cell Immunol. 66: 372–382, 1982.
 109. Lowe, N. J., A. K. Verma, and R. K. Boutwell. Ultraviolet light induces ornithine decarboxylase activity. J. Invest. Dermatol. 71: 417–418, 1978.
 110. Luger, T. A., and T. Schwarz. Therapeutic use of cytokines in dermatology. J. Am. Acad. Dermatol. 24: 915–926, 1991.
 111. MacLaughlin, J. A., and M. F. Holick. Aging decreases the capacity of human skin to produce vitamin D3. J. Clin. Invest. 76: 1536–1538, 1985.
 112. Maize, J. C., and G. Foster. Age related changes in melanocytic nevi. Clin. Exp. Dermatol. 4: 49–55, 1979.
 113. Makinodan, T., and M. M. B. Kay. Age influence on the immune system. Adv. Immunol. 29: 287–330, 1980.
 114. Marks, R. Measurement of biological aging in the human epidermis. Br. J. Dermatol. 104: 627–633, 1981.
 115. Martin, G. M., C. A. Sprague, and C. J. Epstein. Replicative lifespan of cultivated human cells: effect of donor's age, tissue, and genotype. Lab. Invest. 23: 86–92, 1970.
 116. Mendoza, C. B., R. W. Postlethwit, and W. D. Johnson. Incidence of wound disruption following operation. Arch. Surg. 101: 396–398, 1970.
 117. Model, D. Smoker's faces: who are the smokers? Br. J. Med. 291: 1755, 1985.
 118. Montagna, W. W., Morphology of the aging skin: cutaneous appendages. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6., p. 1–16.
 119. Montagna, W., and K. Carlisle. Structural changes in aging human skin. J. Invest. Dermatol. 73: 47–53, 1979.
 120. Murai, A., T. Miyahawa, and S. Shiozawa. Age related variation in glycosylation of hydroxylysine in human and rat skin collagen. Biochim. Biophys. Acta 498: 132–142, 1977.
 121. Nagel, J. E., F. J. Chrest, and W. W. H. Adler. Enumeration of T lymphocyte subsets by monoclonal antibodies in young and aged humans. J. Immunol. 127: 2086–2088, 1981.
 122. Newell, G. R., M. R. Spitz, and J. G. Sider. Cancer and age. Semin. Oncol. 16: 3–9, 1989.
 123. Oberste‐Lehn, H., Effects of aging on the papillary body of the hair follicles and on eccrine sweat glands. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol 6, p. 17–34.
 124. O'Brien, D. H. The induction of ornithine decarboxylase as an early possibly obligatory event in mouse skin carcinogenesis. Cancer Res. 36: 2644–2653, 1976.
 125. O'Dell, B. L., T. Jessen, L. E. Becker, R. T. Jackson, and E. B. Smith. Diminished immune response in sun damaged skin. Arch. Dermatol. 116: 559–561, 1980.
 126. Orentreich, N., and V. J. Selmanowitz. Levels of biological functions with aging. Trans. N. Y. Acad. Sci. 231: 993–1012, 1969.
 127. Ortonne, J. P. Pigmentary changes in aging skin. Br. J. Dermatol. 122 (suppl. 35): 21–28, 1990.
 128. Owen, D. W., and J. M. Knox. Influence of heat, wind, and humidity on ultraviolet radiation injury. Nat. Cancer Inst. Monogr. 50: 161–167, 1978.
 129. Owen, D. W., J. M. Knox, and H. T. Hudson. Influence of wind on ultraviolet injury. Arch. Dermatol. 109: 200–201, 1974.
 130. Owen, D. W., J. M. Knox, and H. T. Hudson. Influence of humidity on ultraviolet injury. J. Invest. Dermatol. 64: 250–252, 1975.
 131. Pachwa, S. G., R. N. Pahwa, and R. A. Good. Decreased in vitro humoral response in aged humans. J. Clin. Invest. 67: 1094, 1102, 1981.
 132. Parrish, J. A., R. R. Anderson, F. Urbach, and D. Pitts. UVA: Biological Effects of Ultraviolet Radiation with Emphasis on Human Responses to Long Wave Ultraviolet. New York: Plenum Publishing, 1978, p. 7–14, 65–73.
 133. Parrish, J. A., K. F. Jaenicke, and A. A. Anderson. Erythema and melanogenesis, action spectra of normal human skin. Photochem. Photobiol. 36: 187–191, 1982.
 134. Pazmino, N. H., and J. M. Yuhas. Senescent loss of resistance to murine sarcoma virus (moloney) in the mouse. Cancer Res. 33: 2668–2672, 1973.
 135. Peacocke, M., M. Yaar, and B. A. Gilchrest. Interferon and the epidermis: implications for cellular senescence. Exp. Gerontol. 24: 415–421, 1989.
 136. Phillips, P. D., and V. J. Cristofalo. A review of recent research on cellular aging in culture. In: Review of Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, p. 385–415, 1987.
 137. Plewig, G. Regional differences in cell sizes in the human stratum corneum. Part II Effects of age and sex on skin. J. Invest. Dermatol. 54: 19–23, 1970.
 138. Plewig, G., and A. M. Kligman. Proliferative activity of the sebaceous glands of the aged. J. Invest. Dermatol. 70: 314–317, 1978.
 139. Plisko, A., and B. A. Gilchrest. Growth factor responsiveness of cultured human fibroblast declines with age. J. Gerontol. 38: 513–518, 1983.
 140. Pochi, P. E., and J. S. Strauss. The effect of aging on the activity of the sebaceous gland in man. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press Inc., 1965, vol. 6, p. 121–127.
 141. Pochi, P. E., J. S. Strauss, and D. T. Downing. Age related changes in sebaceous gland activity. J. Invest. Dermatol. 73: 108–111, 1979.
 142. Potts, R. O., and M. L. Francoeur. The influence of stratum corneum morphology on water permeability. J. Invest. Dermatol. 96: 495–499, 1991.
 143. Praeger, B. In vitro studies of aging. Dermatol. Clin. 4: 359–369, 1986.
 144. Price, G. B., and T. Makinddan. Immunologic deficiencies in senescence. II Characterization of extrinsic deficiencies. J. Immunol. 108: 413–117, 1972.
 145. Quevedo, W. C., G. Szabo, and J. Virks. Influence of age and UV on the populations of DOPA‐positive melanocytes in human skin. J. Invest. Dermatol. 52: 287–290, 1969.
 146. Radl, J., J. M. Sepus, and I. Skvaril. Immunologlobulin patterns in humans over 95 years of age. Clin. Exp. Immunol. 22: 84–90, 1975.
 147. Rasmussen, D. M., K. G. Wakim, and R. K. Winkelmann. Effect of aging on human dermis: studies in thermal shrinkage and tension. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 151–162.
 148. Reed, B. R., and R. A. F. Clark. Cutaneous tissue repair: practical implications of current knowledge. II. J. Am. Acad. Dermatol. 13: 919–936, 1985.
 149. Reenstra, W. R., M. Yaar, and B. A. Gilchrest. The effect of donor age on epidermal growth factor processing in man. Exp. Cell Res. (in press), 1994.
 150. Rees, T. D., D. M. Liverett, and C. L. Guy. The effect of cigarette smoking on skin‐flap survival in the face lift patient. Plast. Reconstr. Surg. 73: 911–915, 1984.
 151. Reus, W. F., M. C. Robson, L. Zachery, and J. P. Heggers. Acute effects of tobacco smoking on blood flow in the cutaneous micro‐circulation. Br. J. Plast. Surg. 37: 213–215, 1984.
 152. Roberts‐Thompson, I. C., S. Whittingham, O. Youngchaiyud, and I. R. Mackay. Aging, immune response and mortality. Lancet 2: 368–370, 1974.
 153. Roskos, K. V., H. I. Maibach, and R. H. Guy. The effect of aging on percutaneous absorption in man. J. Pharmacol. Bio‐Pharmacol. 17: 617–630, 1989.
 154. Sams, W. M., Jr., and J. G. Smith, Jr., Alterations in human dermal fibrous connective tissue with age and chronic sun damage. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 199–210.
 155. Sams, W. M., Jr., J. G. Smith, Jr., and P. G. Burk. The experimental production of elastosis with ultraviolet light. J. Invest. Dermatol. 43: 467–471, 1964.
 156. Sauder, D. N., C. S. Carter, and S. I. Katz. Epidermal cell production of thymocyte activating factor (ETAF). J. Invest. Dermatol. 79: 34–39, 1982.
 157. Sauder, D. N., C. A. Dinarello, and V. B. Morhenn. Langerhan cell production of Interleukin 1. J. Invest. Dermatol. 82: 605–607, 1984.
 158. Sauder, D. N., B. M. Stanulis‐Prager, and B. A. Gilchrest. Autocrine growth stimulation of human keratinocytes by epidermal cell‐derived thymocyte activating factor: implications for skin aging. Arch. Dermatol. Res. 280: 71–76, 1988.
 159. Schuldermann, E., and J. P. Zubeck. Effect of age on pain sensitivity. Percept. Mot. Skills 14: 295, 1964.
 160. Selmanowitz, V. J., K. L. Rizer, and N. Orentreich. Aging of the skin and its appendages. In: Handbook of the Biology of Aging, edited by C. E. Finch and L. Hayflick. New York: Van Nostrand Reinhold, 1977, p. 496.
 161. Setlow, R. B. DNA repair, aging and cancer. Nat. Cancer Monogr. 60: 249–55, 1982.
 162. Sherman, E. D., and E. Robillard. Sensitivity of pain in relationship to age. J. Am. Geriatr. Soc. 12: 1037–1040, 1964.
 163. Shuster, S., M. M. Black, and E. McVitie. The influence of age and sex on skin thickness, skin collagen, and density. Br. J. Dermatol. 93: 639–643, 1975.
 164. Sibert, J. E., Mucopolysaccharides of ground substances. In: Dermatology in General Medicine (2nd ed.), edited by T. B. Fitzpatrick, A. Eisen, K. Wolff, I. Freedberg, K. Austin. New York: McGraw‐Hill, 1979, p. 189.
 165. Silver, A. F., W. Montagna, and I. Karacan. The effect of age on human eccrine sweating. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 129–150.
 166. Singh, J., and A. K. Singh. Age related changes in the human thymus. Clin. Exp. Immunol. 37: 507–511, 1979.
 167. Smith, J. G., E. A. Davidson, W. M. Sams, and R. D. Clark. Alterations in human dermal connective tissue with age and chronic sun damage. J. Invest. Dermatol. 39: 347–350, 1962.
 168. Snider, S. L., and R. R. Kohn. Effects of age and diabetes mellitus on the solubility and nonenzymatic glycosylation of human skin collagen. J. Clin. Invest. 67: 1630–1635, 1981.
 169. Solomon, L. M., and C. Virtue. The biology of cutaneous aging. Int. J. Dermatol. 14: 172–181, 1975.
 170. Stanuus‐Praeger, B. M., M. Yaar, and G. Redziniak. An extract of bovine thymus stimulates human keratinocyte growth in vitro. J. Invest. Dermatol. 90: 749–754, 1988.
 171. Stern, R. S., M. L. Johnson, and J. Delozier. Utilization of physician services for dermatological complaints. Arch. Dermatol. 113: 1062–1066, 1977.
 172. Stoy, P. J., B. Roitman‐Johnson, and G. Walsh. Aging and serum immunoglobulin E levels, immediate skin tests, and RAST J. Allergy Clin. Immunol. 68: 421–426, 1981.
 173. Streilein, J. W. Skin‐associated lymphoid tissues (SALT): origins and functions. J. Invest. Dermatol. 71: 167–171, 1978.
 174. Sullivan, T. J., H. J. Wedner, G. S. Shatz, L. D. Yecies, and C. W. Parker. Skin testing to detect penicillin allergy. J. Allergy Clin. Immunol. 68: 171–174, 1981.
 175. Tagami, H. Functional characteristics of aged skin. Acta Dermatol. (Kyoto) 66: 19–21, 1972.
 176. Tan, C. Y., B. Statham, R. Marks, and P. A. Payne. Skin thickness measurement by pulsed ultrasound: its reproducibility, validation, and variability. Br. J. Dermatol. 106: 657–662, 1982.
 177. Taylor, C. R., R. S. Stern, J. J. Leyden, and B. A. Gilchrest. Photoaging/photodamage and photoprotection. J. Am. Acad. Dermatol. 22: 1–15, 1990.
 178. Uitto, J. A method for studying collagen biosynthesis in human skin biopsies in vitro. Biochim. Biophys. Acta 210: 438–445, 1970.
 179. Uitto, J., M. J. Fazio, and D. R. Olsen. Molecular mechanisms of cutaneous aging. J. Am. Acad. Dermatol. 21: 614–622, 1989.
 180. Uitto, J., J. Halmee, M. Hannuksela, P. Peltokallio, and K. I. Kivinkko. Protocollagen proline hydroxylase activity in the skin of normal human subjects and of patients with scleroderma. Scand. J. Clin. Lab. Invest. 23: 241–247, 1969.
 181. Viljanto, J., and J. Raekallio. Wound healing in children as assessed by the CELLSTIC method. J. Pediatr. Surg. 11: 43–49, 1976.
 182. Vogelstein, B., E. R. Fearon, S. R. Hamilton, S. E. Kern, B. A. Preisinger, M. Leppert, Y. Nakamuram, R. White, A. M. M. Smits, and J. L. Bos. Genetic alterations during colorectal tumor development. N. Engl. J. Med. 319: 525–532, 1988.
 183. Waldorf, D. S., R. F. Wilkens, and J. L. Decker. Impaired delayed hypersensitivity in an aging population. JAMA 203: 831–834, 1968.
 184. Wei, Q., G. M. Matanoski, E. R. Farmer, M. A. Hedayati, and L. Grossman. DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. Proc. Natl. Acad. Sci. U.S.A. 90: 1614–1618, 1993.
 185. Weinstock, M. A. The epidemic of squamous cell carcinoma. JAMA 262: 2138–2140, 1989.
 186. Weksler, M. E., J. B. Innis, and G. Goldstein. Immunological studies of aging mice and reversal with thymopoitin. J. Exp. Med. 148: 996–1006, 1978.
 187. Whitton, J. T., and J. D. Everall. The thickness of the epidermis. Br. J. Dermatol. 89: 467–476, 1973.
 188. Willett, W. C., and B. MacMahon. Diet and cancer: an overview. N. Engl. J. Med. 310: 633–638, 1984.
 189. Winkelmann, R. K., Nerve changes in aging skin. In: Advances in the Biology of the Skin, edited by W. Montagna. Oxford: Pergamon Press, 1965, vol. 6, p. 51.
 190. Yamaura, H., and T. Matsuzawa. Decrease in capillary growth during aging. Exp. Gerontol. 15: 145–150, 1979.
 191. Yaar, M., A. V. Palleroni, and B. A. Gilchrest. Normal human epidermis contains interferon like proteins. J. Cell Biol. 103: 1349–1354, 1986.
 192. Zacharski, L. R., L. R. Elveback, and J. W. Kinman. Lymphocyte counts in healthy adults. Am. J. Clin. Pathol. 56: 148–150, 1971.
 193. Zelickson, A. S., J. H. Mottaz, B. D. Zelickson, and S. A. Muller. Elastic tissue changes in skin following PUVA therapy. J. Am. Acad. Dermatol. 3: 186–192, 1980.

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Article Title: Skin
 

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Anjali Chuttani, Barbara A. Gilchrest. Skin. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 309-324. First published in print 1995. doi: 10.1002/cphy.cp110111