Aging-Like Skin Changes Induced by Ultraviolet Irradiation in an Animal Model of Metabolic Syndrome

Abstract

Both physiological skin aging and pathologic photo-aging caused by ultraviolet (UV) irradiation are mediated by latent inflammation and oxidative stress. Although numerous animal skin-aging models have used UV irradiation, most require massive doses or long-term irradiation. To establish a more refined skin-aging model, we focused on an animal model of metabolic syndrome (MS) because MS involves damage to various organs via oxidative stress or inflammation, similar to the changes associated with aging. We hypothesized that MS skin might exhibit more aging-like changes after milder, shorter-term UV irradiation than would normal animal skin under similar conditions, thus providing a useful model for skin aging. The authors therefore examined the skin from Tsumura Suzuki obese diabetic (TSOD) mice (MS model) and control Tsumura Suzuki non-obese (TSNO) mice before and after UV irradiation. Skin from TSOD mice had a thinner epidermis and dermis, a thicker fatty layer, reduced density and convolution of the fragmented collagen fibers, and upregulated expression of tumor necrosis factor (TNF)-α, a dual marker for inflammation and aging, compared to the skin from TSNO mice. UV irradiation affected TSOD skin more severely than TSNO skin, resulting in various changes resembling those in aged human skin, including damage to the dermis and subcutaneous fatty tissue, infiltration of inflammatory cells, and further upregulation of TNF-α expression. These results suggest that UV-irradiated TSOD mice may provide a new model of skin aging and imply that skin from humans with MS is more susceptible to UV- or aging-related damage than normal human skin.

Aging‐like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling

“…As reported previously (Akase et al, 2012), histological observation revealed that the skin of TSOD mice 24 h after UV irradiation showed greater susceptibility to UV (Fig. 1A-D) with remarkable infiltration of inflammatory cells (arrowheads in Fig.…”

“…In our aging-like skin model, we used 12-week-old male Tsumura-Suzuki obese diabetes (TSOD) mice (Hirayama et al, 1999;Suzuki et al, 1999;Akase et al, 2011Akase et al, , 2012. Twelve-week-old male Tsumura-Suzuki nonobesity (TSNO) mice were used as the non-MetS control.…”

“…We previously found that the skin of MetS model mice was more susceptible to UV than the normal mouse skin (Akase et al, 2012). Based on this finding, we established our own aging-like skin model using the single 90 min UV irradiation onto the MetS mouse skin and confirmed increased expression of tumor necrosis factor (TNF)-a, a dual marker for inflammation and aging, in this model (Akase et al, 2012).…”

“…1D). Taken together with TNF-a upregulation in the TSOD +UV group as reported previously (Akase et al, 2012), we designated this group as the aging-like skin model.…”

“…It is known that disruption of various lifespan determinant pathways such as silent information regulator (SIR)T1 and p99Shc leads to features of MetS in mice, and the same molecular mechanisms may be at least partially active in human with MetS (Fadini et al, 2011), suggesting close relationship between aging and MetS. We previously found that the skin of MetS model mice was more susceptible to UV than the normal mouse skin (Akase et al, 2012). Based on this finding, we established our own aging-like skin model using the single 90 min UV irradiation onto the MetS mouse skin and confirmed increased expression of tumor necrosis factor (TNF)-a, a dual marker for inflammation and aging, in this model (Akase et al, 2012).…”