**3. Photosensitizing reactions and photosensitizing components that occur in the presence of oxygen molecules**

Under certain circumstances, endogenous photosensitizers, such as porphyrins, melanin, urocanic acid, bilirubin, flavins, pterins, and amino acid, such as tryptophan, act as photosensitizers [31–33]. Photosensitization, such as melanin and bilirubin, out of the major pigments of the skin, are known as the major absorbers of visible regions of the spectrum over 300 to 600 nm. On the other hand, other photosensitizers, such as urocanic acid (250 to 300 nm), riboflavin (355 nm), and pterin (345 to 375 nm), show maximum absorption in the UV range and are hardly absorbed in the visible region of the spectrum [34, 35]. Photosensitized reactions involving oxygen molecules are reported as either type I or type II. Previously, the definition of type II reaction involved the formation of singlet oxygen (major reaction) and superoxide (minor reaction) [36, 37]. Currently, it was revised, and the definition of type I reaction now involves the formation of superoxide because we define type I on the basis of the formation of radicals. Type II is now established as the sensitized formation of singlet oxygen. This review followed the definition of guidelines in Baptista et al. [38].

Dermal fibroblasts are often used as a research target for skin aging [39]. The senescence of dermal fibroblasts is thought to have a significant effect on dermal matrix metabolism and degenerate dermal structure [40]. It is well-known that matrix degradation by activation of matrix metalloproteinases (MMPs) contributes to the formation of wrinkles and sagging skin [41]. In addition, it has been reported that aging fibroblasts, which showed an increase of SA-β-galactosidase [42], intercellular ROS, p16 expression [43], DNA damage, and other typical cellular senescence phenotypes, are present in the dermis at the photoaging site. *In vitro*, UVA and UVAphotocatalysts are often used to induce cellular senescence (**Figure 3**). Thus, the ROS generated by photosensitization reactions are considered to be important targets for the development of anti-photoaging agents.

#### **Figure 3.**

*Senescence phenotype of fibroblast induced by UVA irradiation in vitro: Repeated UVA irradiation of human dermal fibroblasts at a dose of 36 J/cm<sup>2</sup> /10 days in the condition of riboflavin coexisted to amino acids and vitamins induced typical phenotype of cellular senescence. Left: Flattened and larger cells have a greater diameter ratio compared to nonirradiated control cells (calcein-AM staining). Center: Increased of blue coloration cells (senescence-associated β-galactosidase staining) compared to nonirradiated control cells. Right: Increased higher level of green fluorescence intensity (dihydrorhodamine 123 staining) compared to nonirradiated control cells. Scale bar; 200 μm.*
