RETINAL AGE PIGMENTS GENERATED BY SELF-ASSEMBLING LYSOSOMOTROPIC DETERGENTS

A UNIVERSAL biomarker of cellular ageing in eukaryotic post-mitotic cells is the appearance over time of autofluorescent lysosomal residual bodies called age pigments or lipofuscin granules1. Their role in the process of cellular ageing has been debated without resolution2. Neither the identity nor mechanism of formation of the fluorophores has been definitively determined. A post-mitotic cell type that accumulates large quantities of age pigments is the ocular retinal pigment epithelium2. We have now identified the major orange-emitting fluorophore of these pigments using fast-atom bombardment tandem mass spectrometry with collisional activation analysis4. It is an amphoteric quaternary amine that arises as a Schiff base reaction product of retinaldehyde and ethanolamine. This compound should display lysosomotropic detergent behaviour which would help explain many of the age-related changes shown in this cell. These results suggest a new role for Schiff base reaction products as lysosomotropic amines in the genesis of cellular age pigments.