Time for a change

Abstract

expression in skin fibroblasts. Chronic UVA exposure is responsible for most of the skin damage associated with photoageing, including specific histone acetylation changes. 6 Recent research has further confirmed that inhibition of histone deacetylases is an effective approach for modulating expression of this water channel protein. 7 More importantly, Xie et al. demonstrate that a short-term effect of chronic UVA (which is comparable with mild sun exposure) is increased autophagy activation and consequently reduced senescence in skin fibroblasts. Further research in keratinocyte lineages is needed to confirm this crucial concept, which would strengthen the beneficial role of autophagy in protection from skin photoageing. According to their model, increased AQP3 expression, transcriptionally regulated by Jun, facilitates the interaction of this channel protein with the scaffold protein DEDD (death effector domain-containing protein), which itself promotes autophagy activation via interaction with PI3KC3. 8 Although the dynamic described here is the opposite (AQP3 interaction leads to DEDD degradation, while still promoting autophagy), Xie et al. provide further evidence that AQP3 can bind and stimulate Beclin1, another key autophagy regulator.This study clearly shows that increased AQP3 expression attenuates long-term UVA-induced senescence in skin fibroblasts by promoting autophagy. This concept is reinforced by the evidence that treatment with rapamycin (an autophagy inducer) can ameliorate the aged phenotype in a UVA-induced skin photoageing mouse model. Overall, the mechanism presented here supports a recently described mouse model of Cockayne syndrome, a genetic disorder characterized by premature ageing where mice display accumulation of autophagy-related proteins and lysosomal dysfunction in their skin when exposed to UV light. 9 Histone deacetylase inhibition successfully prevented subcutaneous fat loss and rescued autophagic/lysosomal dysfunction. It would be interesting to explore whether changes in AQP3 expression could be involved in this mechanistic model too. In the meantime, we have learned from this study by Xie et al. that mild sun exposure can stimulate autophagy, maintaining healthy skin.