Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin

Abstract

Skin aging is a complex process influenced by intrinsic and extrinsic factors. Together, these factors affect the structure and function of the epidermis and dermis. Histologically, aging skin typically shows epidermal atrophy due to decreased cell numbers. The dermis of aged skin shows decreased numbers of mast cells and fibroblasts. Fibroblast senescence contributes to skin aging by secreting a senescence-associated secretory phenotype, which decreases proliferation by impairing the release of essential growth factors and enhancing degradation of the extracellular matrix through activation of matrix metalloproteinases (MMPs). Several molecular mechanisms affect skin aging including telomere shortening, oxidative stress and MMP, cytokines, autophagic control, microRNAs, and the microbiome. Accumulating evidence on the molecular mechanisms of skin aging has provided clinicians with a wide range of therapeutic targets for treating aging skin.

Keywords: intrinsic aging; molecular mechanisms; photoaging; skin aging.

Figure 1

Histology of photoaged skin. The predominant histological finding of photodamaged skin is solar elastosis, i.e., basophilic degeneration of elastotic fibers in the dermis. Solar elastosis is separated from the epidermis by a narrow band of normal-appearing collagen (grenz zone), with collagen fibers arranged horizontally (hematoxylin and eosin staining; original magnification 100×). Source: HJ Lee and M Kim.

Figure 2

Schematic illustration of the major signaling pathways involved in the aging process; these pathways decrease the density, thickness, and organization of collagen. Both chronological aging and photoaging induce ROS, which leads to the upregulation of MMPs. ROS, reactive oxygen species; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa B ; AP-1, activated protein 1; MMP, matrix metalloprotease; TNF-α, tumor necrosis factor-α; TGF-β, transforming growth factor-β.

Figure 3

Graphical illustration of possible mechanisms of skin aging. Gradual shortening of telomeres can induce the cellular senescence caused by intrinsic aging. UV exposure induces telomere shortening by producing reactive oxygen species (ROS) in the skin. ROS accumulation results in DNA damage and activation of two major regulatory signaling pathways, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, which induce matrix metalloproteinases activation. In addition, cytokines, such as tumor necrosis factor-α, interleukin (IL)-1, IL-6, IL-18, and Cysteine-rich protein 61 are another important element in the skin aging process. Autophagy and apoptosis might be associated with skin aging. In the field of epigenetics, specific micro RNAs have been reported in aged skin. Finally, studies on the role of the microbiome changed with aging process are being actively conducted.