What is lipofuscin? Defining characteristics and differentiation from other autofluorescent lysosomal storage bodies

Abstract

Lipofuscins, also known as age-pigments, have three defining characteristics: (1) they consist of intracellular secondary lysosomes; (2) they have a yellow autofluorescent emission when excited by near ultraviolet or blue light; and (3) they accumulate during normal senescence. Lysosomal storage bodies with similar fluorescence properties accumulate in various cell types as a result of specific pathological conditions or experimental manipulations. As a class, the latter are often referred to as ceroid pigments. In general, the mechanisms involved in the formation of ceroid pigments cannot be assumed to be closely similar to those involved in lipofuscin formation. In fact, the mechanisms of formation almost certainly differ, not only between lipofuscins and ceroids, but also among different lipofuscins and different ceroids. Presently, the most detailed knowledge about the mechanisms involved in lipofuscin formation come from studies on the retinal pigment epithelium (RPE) of the eye. These studies indicate that at least the autofluorescent constituents of RPE lipofuscin are generated from derivatives of vitamin A that occur in the retina. Oxidative stress to the retina appears to promote the formation of these RPE fluorophores. Whether similar mechanisms are involved in the formation of the lipofuscins that occur in other tissues remains to be determined. The mechanisms involved in RPE lipofuscin fluorophore formation are closely related to metabolic pathways that are specific to the retina. Thus, it appears likely that the mechanisms by which lipofuscins form in other tissues differ fundamentally from those that underlie RPE lipofuscin formation.