**2. UVA-photosensitization reaction and photoaging**

Sunlight is now considered to be one of the most harmful extrinsic factors that can induce ROS production [16]. Other well-known factors include tobacco smoke [17, 18], PM2.5, and air pollutants [19, 20]. The spectrum of sunlight includes infrared energy (greater than 760 nm), visible light (400–760 nm), and ultraviolet (UV) light (less than 400 nm). UVs are further classified into UVA (400–315 nm), UVB (315–280 nm), and UVC (280–100 nm) [21]. Photobiological reactions are primarily produced by exposure to UVB and UVA radiation. UV is a major cause of DNA damage in the epidermal skin cells [22, 23]. Furthermore, UV rays contribute to change in the stem cell niche, which can lead to photoaging [1, 24]. UVA accounts for about 95% of the UV rays that reach the surface of the ground and is likely to contribute to the risk of the initiation of human skin cancer [25].

#### **Figure 1.**

*Photoaging of the skin: Photoaging of the dermis is mainly induced by long-term UV exposure. UVA, a longwavelength ultraviolet light, causes serious damage to the dermal skin due to ROS produced by the reaction with photosensitizers in the body. Sens\*: Activated photosensitizers.*

UVA indirectly damages DNA [26], in contrast to UVB, which is absorbed by DNA and causes direct cytotoxicity [27]. UVA-induced damage is mainly caused through interactions with the photosensitizers, which produce ROS [28]. UVA causes various changes in the dermis, which appear to be primarily involved in the initiation and progression of photoaging. These photosensitizers absorb photons/energy, resulting in a photosensitizer excited state called the singlet excited state [29, 30]. Two reactions can occur following this first reaction. One is a reaction that emits either heat or fluorescence and returns to the ground state, and the other is a triplet excited state due to intersystem crossing. This triplet excited state reacts with both DNA and molecular oxygen, resulting in DNA modification or the production of ROS, such as superoxide, hydroxyl radical, singlet oxygen, and hydrogen peroxide [31]. The term "photoaging" was coined to emphasize the importance of UV and the resulting ROS formation in the skin-aging process (**Figure 2**) [32].

#### **Figure 2.**

*Scheme of photosensitization and Photoaging: UVA that penetrates the epidermis and reaches the dermis is absorbed by the photosensitizers in the skin tissue and produces ROS under existing O2 molecules.*
