Elastin in the extracellular matrix is important in determining the elasticity of tissue. That elasticity is lost with age, as elastin structure changes in detrimental ways. Because the structure of elastin in tissue is complex, and largely only laid down during development, it seems likely that the best path towards repairing it in old tissues is some form of coercing or reprogramming cells to maintain the elastin structure as they did during the developmental portion of life. As yet, few approaches have made any meaningful inroads in this direction. A few small molecules like minoxidil appear to provoke elastin deposition to some degree, while the biotech company Elastrin is working on a way to remove damaged elastin molecules. This is an important topic, as loss of elasticity in blood vessels is a contributing factor in cardiovascular disease, but as yet is not receiving sufficient attention.
Aging-related degeneration of elastic fibres causes skin wrinkles and loss of elasticity. A correlation has been reported between dermal elastic fibre degradation and wrinkles. However, the mechanism of wrinkle formation is complex and unclear. To establish methods for treating wrinkles, it is necessary to understand the aging-related morphological alterations underlying elastin fibre degradation or disappearance. Recently, three-dimensional (3D) imaging combined with decolourization and fluorescent immunostaining has been used to facilitate the visualization of several tissues, organs, and whole mice. In this study, we aimed to apply the decolourization technique to excised human skin tissue and to observe the 3D structure of elastin fibres. Moreover, to evaluate the elastin fibre structure objectively and quantitatively, we established a computational 3D structural analysis method for 3D imaging.
The 3D observations of the inner skin structures revealed that the structures in the abdominal and eyelid tissues were fundamentally different. In the abdominal skin, oxytalan fibres, which are rich in fibrillin-1, exhibiting a candelabra-like structure, were observed just below the basement membrane, as previously reported. However, in the eyelid skin, a complex entangled network of elastin fibres was observed below the basement membrane, which did not show the candelabra-like structure. The image observation and analysis indicated that the proportion of fibrillin-1 in the eyelid skin was higher than that in the abdomen skin. Although it was unclear whether these differences were due to congenital differences during tissue development or acquired differences due to ultraviolet rays and mechanical movements, it was interesting to understand the mechanism of elastin fibre formation.
In the aged skin from the eyelid and abdomen, the elastin fibres had a short, shrunk and spherical shape compared to the young skin. Because these alterations were common in the eyelid and abdominal skin, they might be because of the intrinsic and chronic physiological process of aging, ischemia, and inflammation and might not depend on characteristic differences, such as on the effects of ultraviolet (UV) irradiation or mechanical irritation, between body parts. In contrast, although these altered parameters were common in the eyelid and abdominal skin, the degree of alteration with age was more significant in the eyelid skin. In addition, the number of fibre branches decreased with aging in the eyelid skin but not in the abdominal skin. It has been reported that the fibrous structure of the skin is associated with wrinkle formation and skin elasticity.
Truncation of fibrillin-rich microfibrils in photo-exposed skin, visualized in 2D, has been reported. The 3D observation and computational analysis performed in this study further support the previous data. Elastin-degrading enzymes, UV-induced reactive oxygen species and frequent mechanical movements might cause these changes in elastin fibres in the eyelid skin. Alternatively, it might also be due to the differences in basic fibre properties, such as the elastin fibre network in the eyelid and the high content of fibrillin-1, as mentioned above.