Abstract
Aging of the skin is a gradual process, which is associated with changes in the appearance, characteristics, and function of the skin. Skin aging occurs through genetic, lifestyle, dietary, and environmental factors. Within the skin the production of collagen and elastin slows down, dead skin cells do not shed quickly, and the turnover of new skin cells decreases between the age group of 20 and 50. In addition to natural aging premature aging can also result which is due to sunlight exposure, chemical exposure, or other environmental pollutions. Ultraviolet radiation in sunlight damages the elastin and collagen fibers in the skin, which ultimately results in wrinkling of the skin at early stages of life. UV light induces approximately 99% of non-melanoma and 95% of melanoma-type skin cancers in humans. Excessive UV exposure produces genetic mutation that can lead to skin cancer. Skin carcinogenesis by DNA damage is considered a predominant paradigm for UV toxicity. Exposure to UV radiation can activate many oncogenes, which leads to skin cancer. Initiation and progression of skin carcinogenesis mediated by UV radiation involve complex pathways including those of apoptosis, proliferation, autophagy, DNA repair, metabolism, and inflammation. PTEN (phosphatase tensin homolog) is well established as a tumor suppressor gene that induces apoptosis and reduces cell proliferation by inhibition of the P13K/AKT pathway. p53 gene present in humans is being positioned on chromosome number 17 and mutations analyzed in the tumor suppressor gene p53 are one of prior genetic events which lead to the development of cancer in the skin due to exposure to UV rays.
In this chapter we have discussed the mechanism of aging and skin cancer as an integrative phenomenon. We have also discussed briefly regarding the molecular biology methods and computational approaches to study the skin cancer and aging in a greater depth.
Keywords
- Skin cancer
- Aging
- Molecular biology
- Bioinformatics and melanoma
This is a preview of subscription content, access via your institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Bates, D., Maechler, M., & Dai, B. The Ime4 package.
Bernstein, E. F., Brown, D. B., Schwartz, M. D., Kaidbey, K., & Ksenzenko, S. M. (2004, February). The polyhydroxy acid gluconolactone protects against ultraviolet radiation in an in vitro model of cutaneous photoaging. Dermatologic Surgery, 30(2), 189–196.
Brash, D. E., Rudolph, J. A., Simon, J. A., Lin, A., McKenna, G. J., Baden, H. P., Halperin, A. J., & Ponten, J. (1991, November 15). A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proceedings of the National Academy of Sciences, 88(22), 10124–10128.
Calles, C., Schneider, M., Macaluso, F., Benesova, T., Krutmann, J., & Schroeder, P. (2010, June 1). Infrared a radiation influences the skin fibroblast transcriptome: Mechanisms and consequences. Journal of Investigative Dermatology, 130(6), 1524–1536.
Chen, Y., & Struhl, G. (1996, November 1). Dual roles for patched in sequestering and transducing hedgehog. Cell, 87(3), 553–563.
Cho, S., Shin, M. H., Kim, Y. K., Seo, J. E., Lee, Y. M., Park, C. H., & Chung, J. H. (2009, August 1). Effects of infrared radiation and heat on human skin aging in vivo. Journal of Investigative Dermatology Symposium Proceedings, 14(1), 15–19.
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., & Beach, D. (2005, August). Tumour biology: senescence in premalignant tumours. Nature, 436(7051), 642.
Daya-Grosjean, L., Robert, C., Drougard, C., Suarez, H., & Sarasin, A. (1993, April 1). High mutation frequency in ras genes of skin tumors isolated from DNA repair deficient xeroderma pigmentosum patients. Cancer Research, 53(7), 1625–1629.
DeBusk, F. L. (1972, April 1). The Hutchinson-Gilford progeria syndrome: Report of 4 cases and review of the literature. The Journal of Pediatrics, 80(4), 697–724.
Dumaz, N., Drougard, C., Sarasin, A., & Daya-Grosjean, L. (1993, November 15). Specific UV-induced mutation spectrum in the p53 gene of skin tumors from DNA-repair-deficient xeroderma pigmentosum patients. Proceedings of the National Academy of Sciences, 90(22), 10529–10533.
Dunn, J. A., McCance, D. R., Thorpe, S. R., Lyons, T. J., & Baynes, J. W. (1991, February 1). Age-dependent accumulation of N. epsilon.-(carboxymethyl) lysine and N. epsilon.-(carboxymethyl) hydroxylysine in human skin collagen. Biochemistry, 30(5), 1205–1210.
Dutta, A., Ruppert, J. M., Aster, J. C., & Winchester, E. (1993, September). Inhibition of DNA replication factor RPA by p53. Nature, 365(6441), 79.
Fisher, G. J., Kang, S., Varani, J., Bata-Csorgo, Z., Wan, Y., Datta, S., & Voorhees, J. J. (2002, November 1). Mechanisms of photoaging and chronological skin aging. Archives of Dermatology, 138(11), 1462–1470.
Fleming, T. H., Humpert, P. M., Nawroth, P. P., & Bierhaus, A. (2011). Reactive metabolites and AGE/RAGE-mediated cellular dysfunction affect the aging process–a mini-review. Gerontology, 57(5), 435–443.
Glass, D., Viñuela, A., Davies, M. N., Ramasamy, A., Parts, L., Knowles, D., Brown, A. A., Hedman, Å. K., Small, K. S., Buil, A., & Grundberg, E. (2013, July). Gene expression changes with age in skin, adipose tissue, blood and brain. Genome Biology, 14(7), R75.
Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. Journal of Gerontology, 11, 298–300.
Hutchinson, F. (1994, August 1). Induction of tandem-base change mutations. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 309(1), 11–15.
Kolesnikov, N., Hastings, E., Keays, M., Melnichuk, O., Tang, Y. A., Williams, E., Dylag, M., Kurbatova, N., Brandizi, M., Burdett, T., & Megy, K. (2014, October 31). ArrayExpress update – Simplifying data submissions. Nucleic Acids Research, 43(D1), D1113–D1116.
Kollias, N., & Baqer, A. (1984, May). An experimental study of the changes in pigmentation in human skin in vivo with visible and near infrared light. Photochemistry and Photobiology, 39(5), 651–659.
Li, C., Chi, S., & Xie, J. (2011, August 1). Hedgehog signaling in skin cancers. Cellular Signalling, 23(8), 1235–1243.
Liebel, F., Kaur, S., Ruvolo, E., Kollias, N., & Southall, M. D. (2012, July 1). Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes. Journal of Investigative Dermatology, 132(7), 1901–1907.
Maier, J. A., Statuto, M., & Ragnotti, G. (1993, September 1). Senescence stimulates U937-endothelial cell interactions. Experimental Cell Research, 208(1), 270–274.
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007, July). A new multipoint method for genome-wide association studies by imputation of genotypes. Nature Genetics, 39(7), 906.
Maser, R. S., & DePinho, R. A. (2002, July 26). Connecting chromosomes, crisis, and cancer. Science, 297(5581), 565–569.
Ouhtit, A., Gorny, A., Muller, H. K., Hill, L. L., Owen-Schaub, L., & Ananthaswamy, H. N. (2000, December 1). Loss of Fas-ligand expression in mouse keratinocytes during UV carcinogenesis. The American Journal of Pathology, 157(6), 1975–1981.
Pinnell, S. R. (2003, January 1). Cutaneous photodamage, oxidative stress, and topical antioxidant protection. Journal of the American Academy of Dermatology, 48(1), 1–22.
Rosengardten, Y., McKenna, T., Grochová, D., & Eriksson, M. (2011 December). Stem cell depletion in Hutchinson–Gilford progeria syndrome. Aging Cell, 10(6), 1011–1020.
Schieke, S. M., Schroeder, P., & Krutmann, J. (2003, October). Cutaneous effects of infrared radiation: From clinical observations to molecular response mechanisms. Photodermatology, Photoimmunology & Photomedicine, 19(5), 228–234.
Sibley, K., Rollinson, S., Allan, J. M., Smith, A. G., Law, G. R., Roddam, P. L., Skibola, C. F., Smith, M. T., & Morgan, G. J. (2003, August 1). Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Research, 63(15), 4327–4330.
Sklar, L. R., Almutawa, F., Lim, H. W., & Hamzavi, I. (2013). Effects of ultraviolet radiation, visible light, and infrared radiation on erythema and pigmentation: A review. Photochemical & Photobiological Sciences, 12(1), 54–64.
Stanulis-Praeger, B. (1987, March 1). Cellular senescence revisited: A review. Mechanisms of Ageing and Development, 38(1), 1–48.
Swisshelm, K., Ryan, K., Lee, X., Tsou, H. C., Peacocke, M., & Sager, R. (1994). Down-regulation of retinoic acid receptor beta in mammary carcinoma cell lines and its up-regulation in senescing normal mammary epithelial cells. Cell Growth & Differentiation, 5(2), 133–141.
Trautinger, F. (2001, October). Mechanisms of photodamage of the skin and its functional consequences for skin ageing. Clinical and Experimental Dermatology, 26(7), 573–577.
Valacchi, G., Fortino, V., & Bocci, V. (2005). The dual action of ozone on the skin. The British Journal of Dermatology, 153, 1096–1100.
Viña, J., Borrás, C., & Miquel, J. (2007). Theories of ageing. IUBMB Life, 59(4–5), 249–254.
Wakabayashi, Y., Mao, J. H., Brown, K., Girardi, M., & Balmain, A. (2007, February). Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the patched gene in FVB mice. Nature, 445(7129), 761.
West, M. D., Pereira-Smith, O. M., & Smith, J. R. (1989, September 1). Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity. Experimental Cell Research, 184(1), 138–147.
Xie, J., Murone, M., Luoh, S. M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J. M., Lam, C. W., Hynes, M., Goddard, A., & Rosenthal, A. (1998, January). Activating smoothened mutations in sporadic basal-cell carcinoma. Nature, 391(6662), 90.
Zhu, P., Ren, M., Yang, C., Hu, Y. X., Ran, J. M., & Yan, L. (2012, February). Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes. Experimental Dermatology, 21(2), 123–129.
Ziegler, A., Jonason, A. S., Leffellt, D. J., Simon, J. A., Sharma, H. W., Kimmelman, J., Remington, L., Jacks, T., & Brash, D. E. (1994, December). Sunburn and p53 in the onset of skin cancer. Nature, 372(6508), 773.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Singh, B., Malhotra, H., Kumar, D., Mujtaba, S.F., Upadhyay, A.K. (2019). Understanding Cellular and Molecular Events of Skin Aging and Cancer: An Integrative Perspective. In: Dwivedi, A., Agarwal, N., Ray, L., Tripathi, A. (eds) Skin Aging & Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-13-2541-0_2
Download citation
DOI: https://doi.org/10.1007/978-981-13-2541-0_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-2540-3
Online ISBN: 978-981-13-2541-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)