Molecular Mechanisms of Dermal Aging and Antiaging Approaches - PubMed (original) (raw)

Review

Molecular Mechanisms of Dermal Aging and Antiaging Approaches

Jung-Won Shin et al. Int J Mol Sci. 2019.

Abstract

The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-β signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. The changes in the levels of GAGs and PGs are highly diverse, and previous studies have reported conflicting results. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. This review summarizes the current understanding of skin aging at the molecular level, and associated treatments, to put some of the new antiaging technology that has emerged in this rapidly expanding field into molecular context.

Keywords: collagen; dermal aging; elastic fiber; fibroblast; glycosaminglycans; hyaluronic acid; proteoglycans.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Schematic illustration showing the changes in fibroblasts, collagen, and elastic fibers in the dermal aging process. Reactive oxygen species (ROS) generated in the aging process activate mitogen-activated protein kinases (MAPKs) and induce transcription factors, including activator protein 1 (AP-1) and nuclear factor-κB (NF-κB). This activation increases matrix metalloproteinase (MMP) expression and inhibits transforming growth factor-β (TGF-β) signaling, which leads to collagen fragmentation and decreased collagen biosynthesis. This hinders the mechanical interaction between fibroblasts and the extracellular matrix (ECM), and consequently reduces the size of dermal fibroblasts. Aged fibroblasts produce a greater amount of ROS that further increases the expression of MMPs and inhibits TGF-β signaling, creating a positive feedback loop that accelerates dermal aging. MMP-12 secreted from fibroblasts and macrophages plays a crucial role in the development of solar elastosis and in the reduction of functional elastic fibers.

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References

    1. Farage M.A., Miller K.W., Elsner P., Maibach H.I. Intrinsic and extrinsic factors in skin ageing: A review. Int. J. Cosmet. Sci. 2008;30:87–95. doi: 10.1111/j.1468-2494.2007.00415.x. - DOI - PubMed
    1. Zeng J.P., Bi B., Chen L., Yang P., Guo Y., Zhou Y.Q., Liu T.Y. Repeated exposure of mouse dermal fibroblasts at a sub-cytotoxic dose of uvb leads to premature senescence: A robust model of cellular photoaging. J. Dermatol. Sci. 2014;73:49–56. doi: 10.1016/j.jdermsci.2013.08.013. - DOI - PubMed
    1. Varani J., Dame M.K., Rittie L., Fligiel S.E., Kang S., Fisher G.J., Voorhees J.J. Decreased collagen production in chronologically aged skin: Roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am. J. Pathol. 2006;168:1861–1868. doi: 10.2353/ajpath.2006.051302. - DOI - PMC - PubMed
    1. Purohit T., He T., Qin Z., Li T., Fisher G.J., Yan Y., Voorhees J.J., Quan T. Smad3-dependent regulation of type i collagen in human dermal fibroblasts: Impact on human skin connective tissue aging. J. Dermatol. Sci. 2016;83:80–83. doi: 10.1016/j.jdermsci.2016.04.004. - DOI - PubMed
    1. Xia W., Quan T., Hammerberg C., Voorhees J.J., Fisher G.J. A mouse model of skin aging: Fragmentation of dermal collagen fibrils and reduced fibroblast spreading due to expression of human matrix metalloproteinase-1. J. Dermatol. Sci. 2015;78:79–82. doi: 10.1016/j.jdermsci.2015.01.009. - DOI - PubMed

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