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. 2009 Mar;129(3):787-91.
doi: 10.1038/jid.2008.293. Epub 2008 Sep 25.

A new paradigm for the role of aging in the development of skin cancer

Davina A Lewis, Jeffrey B Travers, Dan F Spandau

A new paradigm for the role of aging in the development of skin cancer

Davina A Lewis et al. J Invest Dermatol. 2009 Mar.
No abstract available

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Figures

Figure 1
Figure 1. Keratinocyte UVB response in vitro
At low and high doses of UVB, the activation status of the IGF-1R does not influence the response of keratinocyte to UVB irradiation. However, at intermediate doses of UVB, the response of the keratinocytes following UVB exposure is dependent on the status of the IGF-1R. If the IGF-1R is functionally active, keratinocytes undergo stress-induced premature senescence and the unrepaired DNA damage cannot be passed to progeny. If the IGF-1R is functionally inactive during UVB irradiation, keratinocytes are more likely to undergo apoptosis; however, surviving keratinocytes continue to proliferate in the presence of UVB-damaged DNA.
Figure 2
Figure 2. UVB response of the skin in vivo
The integration of data from our lab on the role of the IGF-1R and normal UVB response of keratinocytes (Figure 1) with our data describing the declining production of IGF-1 by senescent fibroblasts has led to the following hypothesis correlating aging skin with the development of skin cancer. Because the production of IGF-1 is silenced in aged skin, aged skin keratinocytes are provided with a reduced supply of IGF-1. Keratinocytes in aged epidermis exposed to UVB wavelengths in sunlight respond inappropriately to the UVB exposure. Instead of undergoing premature stress-induced senescence, the aged keratinocytes may continue to proliferate in the presence of UVB-damaged DNA. We believe this decrease in IGF-1 expression with advancing age is a contributor to the increase in nonmelanoma skin cancer seen in geriatric patients.
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