## 6 Grape and Winery By-Products: Active Ingredients in Cosmeceuticals  
### Anti-Aging and Anti-Wrinkle Properties  
The anti-aging effect of grape and winery by-products has been demonstrated by several studies, due to their ability to inhibit the action of enzymes associated with aging [75; 76]. It seems that grape and winery by-products have a positive impact on the action of tyrosinase, collagenase (MMP-1), and elastase, which are involved in the skin aging process [75; 76; 77]. Specifically, it has been demonstrated that different grape-related products such as grape by-products, extracts of wine lees from alcoholic fermentation, wine lees from vinification, and red grape pomace are evaluated for their antioxidant capacity and their ability to combat hyperpigmentation [75]. Wine lees extracts, rich in phenolic compounds and anthocyanins, were evaluated for their anti-aging and cosmetic properties as depicted in Table 3. The extracts showed strong inhibition of elastase and MMP-1 enzymes, with activity strongly linked to their phenolic content and specific compounds like catfaric acid, malvidin, peonidin-3-O-glucoside, myricetin, and quercetin. Additionally, the extracts inhibited tyrosinase, the key enzyme for melanin synthesis, highlighting their potential use in cosmetic products against hyperpigmentation [75]. Another study conducted on six different grape by-product extracts revealed the anti-aging activity of these extracts. Their anti-aging activity was calculated by tyrosinase inhibition assays and elastase inhibition. The results, although having significant differences between the six extracts, showed that they have greater effect on elastase inhibition than on tyrosinase inhibition. This study also demonstrates the value of grape by-product extracts for cosmetics aimed at reducing wrinkles [76]. A study in vitro [78] examined the effect of grape extract (_Vitis vinifera_ L.) on human dermal fibroblasts exposed to ultraviolet radiation (UVA) stress. The results showed that the extract promotes the expression of SIRT1 and HSP47 genes, which are associated with anti-aging of the skin, under both normal and UVA conditions [79; 80]. At the same time, it modifies DNA methylation in the promoters of these genes, enhancing their gene expression. In addition, the extract improved cell viability by increasing intracellular ATP levels and provided protection against the damaging effects of oxidative stress caused by UVA radiation. Overall, grape extract shows strong protective and anti-aging propositions, making it a promising raw material for the creation of cosmetics [78]. In addition, one more study evaluated the anti-aging properties of _Vitis vinifera_ L. leaf extract (a grape by-product) on human keratinocytes (HaCaT). The findings demonstrated that the extract offers protection against UVA-induced damage by reducing oxidative stress through antioxidant mechanisms, such as lowering ROS levels and protecting DNA, as assessed by the Comet assay and \(\gamma\)-H2 AX markers. Additionally, it enhanced apoptosis, acting as an anti-mutagenic factor. Although protection against UVB was limited at low doses, the results highlight the extract's potential in developing products with anti-aging and protective properties [20].