UVA Exposure Combined with Glycation of the Dermis Are Two Catalysts for Skin Aging and Promotes a Favorable Environment to the Appearance of Elastosis

Abstract

Skin aging is the result of superimposed intrinsic (individual) and extrinsic (e.g., UV exposure or nutrition) aging. Previous works have reported a relationship between UV irradiation and glycation in the aging process, leading, for example, to modified radical species production and the appearance of AGEs (advanced glycosylation end products) in increasing quantities, particularly glycoxidation products like pentosidine. In addition, the colocalization of AGEs and elastosis has also been observed. We first investigated the combination of the glycation reaction and UVA effects on a reconstructed skin model to explain their cumulative biological effect. We found that UVA exposure combined with glycation had the ability to intensify the response for specific markers: for example, MMP1 or MMP3 mRNA, proteases involved in extracellular matrix degradation, or proinflammatory cytokine, IL1α, protein expression. Moreover, the association of glycation and UVA irradiation is believed to promote an environment that favors the onset of an elastotic-like phenomenon: mRNA coding for elastin, elastase, and tropoelastin expression is increased. Secondly, because the damaging effects of UV radiation in vivo might be more detrimental in aged skin than in young skin due to increased accumulation of pentosidine and the exacerbation of alterations related to chronological aging, we studied the biological effect of soluble pentosidine in fibroblasts grown in monolayers. We found that pentosidine induced upregulation of CXCL2, IL8, and MMP12 mRNA expression (inflammatory and elastotic markers, respectively). Tropoelastin protein expression (elastin precursor) was also increased. In conclusion, fibroblasts in monolayers cultured with soluble pentosidine and tridimensional in vitro skin constructs exposed to the combination of AGEs and UVA promote an inflammatory state and an alteration of the dermal compartment in relation to an elastosis-like environment.

Research Advances on the Damage Mechanism of Skin Glycation and Related Inhibitors

“…UVA irradiation combined with AGEs enhances MMP1 and MMP3 mRNA expression, which induces protein expression of fibrin 1 and tropoelastin and reduces the expression of glyoxalase, which detoxifies harmful precursors of AGEs. Because glycated collagen and elastin are highly resistant to MMP degradation, a large accumulation of glycated proteins [ 93 ] leads to skin aging and elastic tissue proliferation [ 94 ]. In addition, keratinocytes secrete AGEs in response to UV irradiation, which stimulates melanin production through ERK and CREB signaling of RAGE, leading to skin pigmentation [ 95 ].…”

Perieccrine Coil Elastosis: An Unusual and Previously Unrecognized Aging-Related Phenomenon

“…The association of glycation and UV irradiation in the aging process leads to increased amounts of advanced glycation end products (AGEs) and the latter favors elastosis. 4 We report a case of perieccrine coil elastosis, an unusual phenomenon that to the best of our knowledge has not been reported, associated with an infiltrative basal cell carcinoma (BCC).…”

“…The association of glycation and UV irradiation in the aging process leads to increased amounts of advanced glycation end products (AGEs) and the latter favors elastosis. 4…”

Evaluation of human skin response to solar‐simulated radiation in an ex vivo model: Effects and photoprotection of L‐Carnosine

“…14 Several studies demonstrate that oxidative stress generated in UV-exposed skin may accelerate the glycation products formation and amplify the local degenerative phenomena associated with the aging process. [15][16][17] Another important point consists in the molecular consequences of solar exposure, which may affect the transcriptional profile of the skin. Many groups investigated cutaneous gene expression changes induced by UV, visible light, sunlight or solar-simulated light exposure, reporting that the mainly modulated genes were related to epidermal differentiation and proliferation processes, which are in turn connected to skin surface alterations, such as hydration and thickening, 18,19 immunity and inflammation, showing the induction of cytokines and interleukins and the reduction of innate immunity genes, 1,4,[20][21][22][23][24][25][26] stress and oxidative stress response with induced expression of genes encoding heat shock proteins, 27,28 and target genes of the cytoprotective to oxidative and electrophilic stress NF-E2-related factor 2 (Nrf2)-pathway.…”