Two types of processes intrinsic and

Two types of processes, intrinsic and extrinsic, contribute synergistically to the age-related change on structural integrity and physiological function of the skin (Farage, Miller, Elsner, & Maibach, 2008). Intrinsic aging arise from genetically programmed cell aging, normal metabolic activities, and hormonal change, which lead to the production of free radicals and accumulation of random mutations (Farage et al., 2008, Makrantonaki and Zouboulis, 2007). The intrinsic skin aging is associated with alteration in gene expression, which seems to be gender dependent (Makrantonaki et al., 2012). However, the gene and protein Chelerythrine Chloride of mediators in Wnt signaling pathway are significantly reduced in aged skin in both male and female, indicating Wnt signaling might play a critical role (Makrantonaki et al., 2012, Zouboulis and Makrantonaki, 2019). Extrinsic aging is caused by environmental factors such as ionizing radiation (i.e. sun exposure, microwaves, and X rays), infectious agents, air pollution, smoking, alcohol intake, overeating, and poor nutrition (Farage et al., 2008). Sunlight, particularly ultraviolet radiation (UVR), is the major extrinsic factor to induce skin aging (Bosch et al., 2015). UVR leads to free radical generation by homolytic cleavage, which initiate lipid peroxidation, DNA strand break, and inflammatory response (Suh et al., 2009). UVR is also known to induce skin aging by activating matrix metalloproteinases (MMP), which digest components of extracellular matrix including collagens, elastin, and fibronectin. Another key cellular abnormity in aged skin is low-grade chronic inflammation (Pillai, Oresajo, & Hayward, 2005), which is involved extensively in both intrinsic and extrinsic skin aging (Fig. 1) (Pasparakis et al., 2014). In terms of lipid synthesis, the shifting of cytokine profile produced by keratinocytes and fibroblasts is believed to play a role in the reduced fat synthesis in subcutaneous fat tissue in both acutely and chronically sun-damaged skin, possibly through transcriptional regulation of transcription factors transcription activator sterol regulatory element binding protein-1, CCAAT/enhancer-binding protein α, and peroxisome proliferator-activated receptor (PPAR)-γ, and subsequent transcription of key lipogenic enzymes such as acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase (Kim et al., 2011). The reduced lipid synthesis in skin is also correlated with the decline of hormone level. In human sebocytes SZ95, lipid production was shown to be significantly reduced when cells are maintained in hormone level comparable to elderly women in comparison to cells treated with hormone level similar to young women, which was accompanied with altered expression of genes in mitochondrial function, oxidative stress, ubiquitin-mediated proteolysis, cell cycle, immune response, steroid biosynthesis, and phospholipid degradation (Makrantonaki et al., 2006). These cellular malfunctions give rise to the physiological changes in aged skin that may include: (1) atrophy of epidermis and dermis; (2) increased cutaneous pH; (3) compromised immune function with increase susceptibility to infection; (4) decreased neurosensory capacity; (5) diminished circulation with vasculature disorganization; (6) reduced vitamin D synthesis; (7) dropped lipid content; (8) impaired injury repair; (9) altered permeability (Farage et al., 2013, Sjerobabski-Masnec and Situm, 2010, Waller and Maibach, 2005, Waller and Maibach, 2006).
The importance of lipids in skin Lipids are vital components in skin. Some species of lipid contribute to the barrier function of the epidermal and the formation and maintenance of membrane structure, while others play a key role in cell function as bioactive lipid-derived mediators, which are produced in response to various internal and external stimuli (Jungersted et al., 2008, Kiezel-Tsugunova et al., 2018).