Autophagy as a new strategy to reduce pigmentation

Autophagy is a cellular mechanism which preserves cell health by recycling long-lived proteins and damaged organelles. This catabolic pathway starts with the sequestration of the targeted organelles subject to degradation along with a portion of cytosol into a double- or multi-membrane structure known as phagophore. This structure elongates after closure to form a vesicular structure, termed autophagosome. Subsequently, the mature autophagosome fuses with the lysosome, thereby forming a single membrane structure (autolysosome) where protein degradation is promoted by lysosomal enzymes 1,2 Autophagy constitutively occurs at basal cellular level to ensure the homeostatic turnover of cell components but can also be activated when the cells need to clear potentially toxic cytoplasmic materials or when the cells are under various stress conditions like oxidative stress3 or radiation.4,5 Under these circumstances, altered components are degraded to be subsequently replaced by newly produced ones, allowing the cells and organisms to preserve their physiological functions.

Related to cosmetic objectives, one of the main and oldest fields in which autophagy has been studied is skin ageing, which is probably the main target. It is generally accepted that autophagy activity declines and/or is impaired in aged keratinocytes and fibroblasts.6–11 Activating or maintaining a high autophagic flux over ageing could slow down or reverse skin ageing.12,13 Autophagy has also been implicated in the defence against UV radiation and pollution and several authors demonstrated that autophagy inducers may reduce the detrimental effects of UV, polluting agents – including (benzo[a]pyrene (BaP) and cadmium chloride (CdCl2) – and inflammation.14–18 Recently, autophagy has been involved in sebaceous gland function and sebum composition in mice,19 suggesting that autophagy might play a role in oily skin and acne. Lastly, autophagy has been reported to be also involved in the regulation of melanogenesis and of skin colour. In melanocytes, it controls both the formation and the catabolism of melanosomes in case of defects or disruptions.20 Some reports suggested that autophagy promotes melanosomes degradation in keratinocytes,21,22 – ultimately resulting in a reduction of pigmentation in skin equivalent models and skin explants.21 

Considering the skin colour as an important characteristic in the perception of beauty, its regulation is of great interest. Indeed, depending on the geographical area, a pale and bright skin can be a sign of elegance and beauty. Moreover, regardless of the geographical location, dark spots that appear with age owing to a high and regular UV exposure are widely recognised as a visible sign of ageing.23–25 Therefore, a bright tone and a homogeneous skin colour are perceived as young and beautiful skin parameters, and activating autophagy appears as a promising strategy to get a brightening effect and reduce dark spots.