The aging process leads to a loss of firmness and elasticity in the skin, causing tissues to collapse and the subsequent production of wrinkles. This wrinkle formation involves dramatic structural alterations in the epidermis, dermis and hypodermis. For example, alterations of the hydration state and water-holding capacity of the epidermis have been found to contribute significantly to the formation of wrinkles1 and can easily be associated with a deficiency of water mostly due to the drying activity of environmental factors such as UV, light, heat and pollution.2
The epidermis is mainly composed of keratinocytes, which proliferate in the stratum basale (SB), differentiate and migrate toward the skin surface. The outermost layer of the epidermis, the stratum corneum (SC), is mostly composed of flattened and cornified keratinocytes, which produce high amounts of keratin during the differentiation process. Dead keratinocytes are held together by junctions and microfibrils composed of different insoluble proteins that are essential for the skin’s mechanical integrity and waterproof properties.
Involucrin (INV) and filaggrin (FLG) are two important proteins in the epidermis, and both contribute to the structural integrity of the SC.3 Moreover, FLG is a source of natural moisturizing factors (NMF), as it generates precursors of the NMF upon hydrolysis.4 Another important factor that plays a key role in skin hydration and integrity of the epidermis is aquaporin (AQP); specifically, aquaporin 3 (AQP3), located at the plasma membrane in the SB and stratum spinosum, where it plays an essential role in water transport.5
In the dermis, the fibroblasts are mainly responsible for the production of all the components of the extra-cellular matrix (ECM), such as collagen, elastin, hyaluronan and proteoglycans. The formation of wrinkles is associated with changes in the elastic and supporting proprieties of the ECM, mainly due to the denaturation of the collagen fibers, and/or to an unbalanced ratio of collagen synthesis and degradation.6 Visible signs of aging also appear as the adipocytes present in the hypodermis cannot fill in the skin and compensate for damages in the outer layers. Adipocytes provide volume and help add thickness and suppleness to the skin.7 In time, there is a decline in the capacity of pre-adipocytes to differentiate and of fat cells to create new lipids. This contributes to a decrease in fat mass and to alterations in fat tissue function.8