Antioxidants in Photoaging: From Molecular Insights to Clinical Applications Photoaging (PA) is a condition caused by prolonged exposure to ultraviolet radiation (UVR), leading to skin damage and clinical signs of aging. The skin undergoes physiological renewal, but UVR disrupts the extracellular matrix (ECM) and alters skin cell function, contributing to PA. Key mechanisms include DNA damage, oxidative stress, and activation of cell signaling pathways that impair skin integrity. The medical community has explored antioxidant therapies to counteract PA, as UVR damage exceeds the skin's natural antioxidant defenses. Nutraceuticals and phytochemicals have shown potential antioxidant and photoprotective effects. PA is influenced by factors such as UVR levels, skin type, lifestyle, and ethnicity. The skin's extracellular matrix deteriorates over time, leading to wrinkles, dryness, and loss of elasticity. Oxidative stress from UVR increases reactive oxygen species (ROS), which damage DNA, proteins, and lipids, promoting inflammation and skin damage. TGF-β signaling is crucial in maintaining ECM integrity, but its downregulation contributes to PA. ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, are involved in PA pathophysiology. UVR causes direct DNA damage, leading to mutations and skin cancer. UVB radiation causes DNA damage through covalent bonds in pyrimidine bases, while UVA causes indirect damage via ROS. These effects lead to cellular senescence, inflammation, and ECM degradation. Antioxidants, including vitamins C and E, polyphenols, and carotenoids, help counteract ROS and protect the skin. Clinical studies show that topical and oral antioxidant supplements improve skin appearance, reduce wrinkles, and enhance collagen production. Antioxidants also modulate MMP activity and collagen synthesis, which are key in PA pathophysiology. Marine-derived compounds and phytochemicals, such as cinnamaldehyde and carotenoids, have photoprotective properties. These compounds reduce ROS, inhibit MMPs, and protect against UVR-induced damage. Ozone therapy and physical activity also show potential in PA treatment. This review highlights the molecular mechanisms of PA and the role of antioxidants in its prevention and treatment. Antioxidants are considered essential in PA management due to their ability to protect DNA, reduce oxidative stress, and maintain ECM integrity. While sunscreen use remains critical, antioxidant therapies offer additional benefits in combating PA. Further research is needed to optimize antioxidant formulations and establish their efficacy in clinical practice.Antioxidants in Photoaging: From Molecular Insights to Clinical Applications Photoaging (PA) is a condition caused by prolonged exposure to ultraviolet radiation (UVR), leading to skin damage and clinical signs of aging. The skin undergoes physiological renewal, but UVR disrupts the extracellular matrix (ECM) and alters skin cell function, contributing to PA. Key mechanisms include DNA damage, oxidative stress, and activation of cell signaling pathways that impair skin integrity. The medical community has explored antioxidant therapies to counteract PA, as UVR damage exceeds the skin's natural antioxidant defenses. Nutraceuticals and phytochemicals have shown potential antioxidant and photoprotective effects. PA is influenced by factors such as UVR levels, skin type, lifestyle, and ethnicity. The skin's extracellular matrix deteriorates over time, leading to wrinkles, dryness, and loss of elasticity. Oxidative stress from UVR increases reactive oxygen species (ROS), which damage DNA, proteins, and lipids, promoting inflammation and skin damage. TGF-β signaling is crucial in maintaining ECM integrity, but its downregulation contributes to PA. ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, are involved in PA pathophysiology. UVR causes direct DNA damage, leading to mutations and skin cancer. UVB radiation causes DNA damage through covalent bonds in pyrimidine bases, while UVA causes indirect damage via ROS. These effects lead to cellular senescence, inflammation, and ECM degradation. Antioxidants, including vitamins C and E, polyphenols, and carotenoids, help counteract ROS and protect the skin. Clinical studies show that topical and oral antioxidant supplements improve skin appearance, reduce wrinkles, and enhance collagen production. Antioxidants also modulate MMP activity and collagen synthesis, which are key in PA pathophysiology. Marine-derived compounds and phytochemicals, such as cinnamaldehyde and carotenoids, have photoprotective properties. These compounds reduce ROS, inhibit MMPs, and protect against UVR-induced damage. Ozone therapy and physical activity also show potential in PA treatment. This review highlights the molecular mechanisms of PA and the role of antioxidants in its prevention and treatment. Antioxidants are considered essential in PA management due to their ability to protect DNA, reduce oxidative stress, and maintain ECM integrity. While sunscreen use remains critical, antioxidant therapies offer additional benefits in combating PA. Further research is needed to optimize antioxidant formulations and establish their efficacy in clinical practice.