UVA-induced photoaging inhibits autophagic degradation by impairing lysosomal function in dermal fibroblasts.

Autophagy has been associated with a variety of diseases especially aging. Human dermal fibroblasts (HDFs) can internalize and then degrade elastin, collagen and advanced glycation end products (AGEs) in lysosomes, which plays prominent roles in extracellular matrix homeostasis and AGEs removal in the dermis. Although autophagy has been reported to be decreased in photoaged fibroblasts, the underlying mechanism and its relevance to photoaging remain elusive. Here, we showed that GFP-LC3 puncta per cell, LC3Ⅰ/Ⅱ conversion and p62 expression were significantly increased, whereas beclin1 expression was not altered in UVA-induced photoaged fibroblasts compared with non-photoaged control. Moreover, autophagic flux was not significantly affected by chloroquine treatment, but was remarkably induced by rapamycin treatment in photoaged fibroblasts, suggesting that UVA-induced photoaging might inhibit autophagy at the degradation stage. Further lysosomal function studies demonstrated that degradation of formed autophagosomes, LC3Ⅱprotein and DQ-Green BSA was all dramatically decreased in photoaged fibroblasts. LysoSensor yellow/blue DND 160 staining and flow cytometry assays demonstrated that photoaging obviously attenuated lysosomal acidification. Also, decreased expression of cathepsin B, L and D was found in photoaged fibroblasts. These data suggest that lowered lysosomal acidity and decreased cathepsins expression might contribute to the inhibition of autophagic degradation, which might be crucial in the development of photoaging through impairing intracellular degradation.