LIPOFUSCIN - MECHANISMS OF FORMATION AND INCREASE WITH AGE

Lipofuscin (age pigment) is a brown-yellow, electron-dense, autofluore scent material that accumulates progressively over time in lysosomes o f postmitotic cells, such as neurons and cardiac myocytes. The exact m echanisms behind this accumulation are still unclear. This review outl ines the present knowledge of age pigment formation, and considers pos sible mechanisms responsible for the increase of lipofuscin with age. Numerous studies indicate that the formation of lipofuscin is due to t he oxidative alteration of macromolecules by oxygen-derived free radic als generated in reactions catalyzed by redox-active iron of low molec ular weight. Two principal explanations for the increase of lipofuscin with age have been suggested. The first one is based on the notion th at lipofuscin is not totally eliminated (either by degradation or exoc ytosis) even at young age, and, thus, accumulates in postmitotic cells as a function of time. Since oxidative reactions are obligatory for l ife, they would act as age-independent enhancers of lipofuscin accumul ation, as well as of many other manifestations of senescence. The seco nd explanation is that the increase of lipofuscin is an effect of agin g, caused by an age-related enhancement of autophagocytosis, a decline in intralysosomal degradation, and/or a decrease in exocytosis.