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Molecules 2017, 22(3), 356; doi:10.3390/molecules22030356

Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin

1
Department of Pharmacology and Toxicology, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, USA
2
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Biochemistry and Molecular Biology Indiana University School of Medicine, Indianapolis, IN 46202, USA
4
Dayton Veterans Affairs Medical Center, Dayton, OH 45428, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Santosh Katiyar
Received: 3 February 2017 / Revised: 22 February 2017 / Accepted: 24 February 2017 / Published: 26 February 2017
(This article belongs to the Special Issue Cancer Chemoprevention)
View Full-Text   |   Download PDF [1815 KB, uploaded 26 February 2017]   |  

Abstract

The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1) by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC. View Full-Text
Keywords: Skin cancer; keratinocyte; insulin-like growth factor-1; UV light; DNA damage; DNA repair; DNA damage response; genomic instability; DNA replication; dermal wounding Skin cancer; keratinocyte; insulin-like growth factor-1; UV light; DNA damage; DNA repair; DNA damage response; genomic instability; DNA replication; dermal wounding
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kemp, M.G.; Spandau, D.F.; Travers, J.B. Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin. Molecules 2017, 22, 356.

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