Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.
Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.
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DOI：
10.3390/molecules22030356
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发表时间：
2017-02-26
期刊：
影响因子：
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通讯作者：
Travers JB
中科院分区：
文献类型：
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作者：
Kemp MG;Spandau DF;Travers JB
非黑色素瘤皮肤癌（NMSC）的发病率不断增加，需要彻底了解其主要风险因素，包括暴露于紫外线（UV）波长的阳光和年龄。虽然紫外线辐射（UVR）长期以来一直被认为会在基因组DNA中产生光产物，促进基因突变，从而驱动皮肤癌的发生，但年龄对疾病发病机制的作用机制了解较少，也没有得到充分的研究。在这篇综述中，我们强调的研究，已考虑年龄作为一个变量，在检查紫外线照射的皮肤DNA损伤反应，然后讨论新出现的证据表明，减少生产的胰岛素样生长因子-1（IGF-1）的衰老成纤维细胞在真皮中的老年皮肤创建一个环境，产生负面影响表皮角质形成细胞如何响应紫外线诱导的DNA损伤。特别是，最近的数据表明，细胞对DNA损伤的反应的两个主要组成部分，包括核苷酸切除修复和DNA损伤检查点信号传导，在具有非活性IGF-1受体的角质形成细胞中均部分缺陷。因此，克服老年皮肤中的这些肿瘤促进条件可能提供一种降低衰老相关皮肤癌风险的方法，因此我们将考虑皮肤创伤和相关临床干预如何使皮肤恢复活力，重新激活IGF-1信号传导，并防止NMSC的启动。
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.