Impact of age and insulin-like growth factor-1 on DNA damage responses in UV-irradiated human skin

Michael G. Kemp, Dan Spandau, Jeffrey Travers

Research output: Contribution to journalReview article

9 Citations (Scopus)

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.

Original languageEnglish (US)
Article number356
JournalMolecules
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

insulin
Somatomedins
DNA Damage
Skin
deoxyribonucleic acid
damage
DNA
Skin Neoplasms
cancer
geriatrics
Keratinocytes
pathogenesis
Ultraviolet radiation
Radiation
Somatomedin Receptors
nucleotides
fibroblasts
sunlight
mutations
ultraviolet radiation

Keywords

  • Dermal wounding
  • DNA damage
  • DNA damage response
  • DNA repair
  • DNA replication
  • Genomic instability
  • Insulin-like growth factor-1
  • Keratinocyte
  • Skin cancer
  • UV light

ASJC Scopus subject areas

  • Medicine(all)
  • Organic Chemistry

Cite this

Impact of age and insulin-like growth factor-1 on DNA damage responses in UV-irradiated human skin. / Kemp, Michael G.; Spandau, Dan; Travers, Jeffrey.

In: Molecules, Vol. 22, No. 3, 356, 01.03.2017.

Research output: Contribution to journalReview article

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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.",
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