Differential Modulation of Autophagy Contributes to the Protective Effects of Resveratrol and Co-Enzyme Q10 in Photoaged Mice.

Abstract

In photoaging, the accumulation of ultraviolet (UV)-induced oxidative damage leads to the characteristic hallmarks of aging. Here arises the importance of autophagy as a cellular degradation process that cleans the cells of defective or aged organelles and macromolecules, thus maintaining cellular homeostasis. In spite of this, the exact impact of autophagy in photoaging is still elusive. To evaluate the protective effects of resveratrol and/or co-enzyme-Q10 against the UVA-induced alterations and to explore the role of autophagy in their proposed benefits. Sixty female mice were randomly divided into normal control, untreated UVA-exposed, resveratrol (50mg/kg), co-enzyme-Q10 (100mg/kg), and resveratrol/co-enzyme-Q10-treated UVA-- exposed groups. Clinical signs of photoaging were evaluated using a modified grading score and the pinch test. Skin malondialdehyde and reduced glutathione were assessed as markers of oxidative stress. Tissues were examined for histopathological signs of photodamage, and autophagic changes were determined by immunohistochemical detection of LC3 and P62 in the different cells of the skin. UVA-exposure increased the oxidative stress with subsequent epidermal and dermal injury. This was associated with the stimulation of autophagy in the keratinocytes and inhibition of autophagic flux in the fibroblasts and infiltrating macrophages. Both drugs corrected the impaired pinch test, macro-and microscopic changes, and exhibited distinct staining patterns with anti-LC3 and P62 in the different cell types denoting autophagic modulation. Changes in autophagic flux are strongly implicated in photoaging associated skin damage and the differential modulation of autophagy by resveratrol and, to a lesser extent by Co-enzyme- Q10, is partially involved in their therapeutic benefits.