Although it is presently accepted that lipofuscin (age-pigment) is the end product of the physiological decay of the cells' own constituents, the intimate mechanisms involved in its formation are largely unknown. The advances in the field of lipofuscinogenesis have been relatively slow, mainly due to the persistent confusion between the naturally occurring normal lipofuscin and the pathologically formed ceroid pigments. Therefore, attempts have been made in this presentation to review first the differential features between these pigments and second, to provide a general overview on the physicochemical properties of lipofuscin. The two prevailing theories on lipofuscinogenesis, the peroxidative theory and the proteolytic decline theory, are critically discussed, and future lines of research are suggested for the resolution of present uncertainties on lipofuscinogenesis. Since lipofuscin is properly considered the hallmark of cellular aging, it is expected that the unraveling of the mechanisms involved in lipofuscin formation will provide important clues to the still unknown underlying causes of cellular aging.
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