## 4 Discussion
They consist of elastin and many elastin-associated microfibrillar proteins that assemble into a complex fiber network [58]. Aging is easily visible as changes in the skin. In normal human skin, the loss of elastic fibers with age results from the loss of skin thickness [59]. Moreover, the loss of skin elasticity with age is caused by the loss of fibroblast cells owing to a reduction in biosynthetic activity and modification of ECM macromolecules [59]. Many genes involved in the response to growth factors, such as _LTBP4_ have also been associated with elastic fibers. The genes highly upregulated by the GP extract encode components of elastic fibers and the ECM. Treatment of human skin cells with GP extract may promote the expression of genes associated with growth factors. Moreover, an increase in growth factor proteins may prevent the aging of human skin. Among the known metabolic pathways, two upregulated genes, _TH_ and _TPH1_ were associated with folate biosynthesis (hsa00790). _TH_ encodes tyrosine hydroxylase, whereas _TPH1_ encodes tryptophan hydroxylase 1. Moreover, _CYP24A1_ encoding cytochrome P450 family 24 subfamily A member 1, is involved in vitamin D metabolism. Several studies have suggested that vitamin D and folate metabolism may be correlated with vascular health and human skin pigmentation [60]. The high expression of these three genes on treatment with the GP extract could cause the accumulation of vitamin D in the skin, and the active metabolites of vitamin D have a wide range of anti-aging and photoprotective effects on the skin [61]. In contrast, the most significant function of the downregulated genes was cell adhesion (GO:0007155). Cell adhesion molecules allow cells to adhere to each other and to the ECM [62]. Therefore, they play important roles in the formation and structural integrity of the epithelium of human skin [63]. Of the identified genes associated with cell adhesion, _DDR2_ encoding discoidin domain receptor 2, a collagen receptor, regulates cell proliferation, and the absence of _DDR2_ results in dwarfism in mouse mutants [64]. Thus, the downregulation of _DDR2_ by the GP extract may have negative effects on cell adhesion. Another identified gene downregulated by GP extract was _ADAMTS18_, which is a member of the disintegration metalloproteinase with thrombospondin domains (ADAMTS) family composed of 19 genes. ADAMTS genes participate in the assembly and degradation of ECM during development, morphogenesis, tissue repair, and remodeling [65]. Loss of _ADAMTS18_ function promotes the growth, migration, and metastasis of melanomas [66]. Thus, the downregulation of _ADAMTS18_ gene expression by GP extract may have a positive effect on cell adhesion. Enriched cellular components in both up- and downregulated genes were associated with the synapse (GO:0045202), neuron projection (GO:0043005), neuron part (GO:0097458), and an intrinsic component of the plasma membrane (GO:0031226). As expected, the GP extract affected the expression of genes associated with the plasma membrane. Notably, many DEGs were associated with neurons. Consistent with our results, previous studies have shown that GP has positive effects on injured spinal motor neurons [67] and neuroprotective effects in a rat model of cardiopulmonary resuscitation [68]. Many upregulated genes were associated with several cell components, such as supramolecular fibers (GO:0099512), Golgi apparatus (GO:0005794), endoplasmic reticulum (GO:0005783), and cytoplasmic region (GO:0099568), and four downregulated genes, _DDR2_, _FAP_, _DAB1_, and _REN_, were specifically associated with the apical part of the cell (GO:0045177). GP extract also induced the expression of genes involved in several metabolic pathways, such as amino acid metabolism, tryptophan metabolism, and heme biosynthesis, which are essential processes in human organs. For example, tryptophan metabolism is highly associated with inflammation, energy homeostasis, and brain function [69].