The Incorporation of Melanosomes by Senescent Keratinocytes Causes the Accumulation of Melanin due to Decreased Energy Metabolism

Abstract

In solar lentigo, a typical age-related pigmentary disorder of the skin, abundant melanin is deposited in the basal layer of keratinocytes and not spontaneously eliminated. The reason for the prolonged melanin accumulation in keratinocytes is not fully understood. Therefore, we focused on the energy metabolism of keratinocytes that incorporate melanosomes, specialized organelles where melanin pigment is synthesized, and investigated the mechanism of melanin accumulation in keratinocytes. Energy metabolism in keratinocytes after the addition of melanosomes was assessed by measuring ATP levels, lactate production, and oxygen consumption rate. Energy limitations after melanosome addition were evaluated by microscopy. Cells with incorporated melanosomes were stained for senescence and proliferation markers. The results showed that keratinocytes upregulated their energy metabolism after melanosome incorporation and energy limitations increased the amount of melanin per cell. Keratinocytes positive for senescence-associated β-galactosidase, a cellular senescence marker, accumulated large amounts of melanin, while keratinocytes positive for 5-ethynyl-2′-deoxyuridine, a proliferation marker, contained little melanin. These findings indicate that senescent keratinocytes tend to accumulate melanin, which may be due to their impaired energy metabolism and thus inability to activate energy metabolism after melanosome incorporation. Our results suggest that melanosome incorporation by senescent keratinocytes causes the persistent melanin deposition in solar lentigo.