Lipofuscin: Mechanisms of age-related accumulation and influence on cell function
2002 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, Vol. 33, no 5, 611-619 p.Article in journal (Refereed) Published
The accumulation of lipofuscin within postmitotic cells is a recognized hallmark of aging occuring with a rate inversely related to longevity. Lipofuscin is an intralysosomal, polymeric substance, primarily composed of cross-linked protein residues, formed due to iron-catalyzed oxidative processes. Because it is undegradable and cannot be removed via exocytosis, lipofuscin accumulation in postmitotic cells is inevitable, whereas proliferative cells efficiently dilute it during division. The rate of lipofuscin formation can be experimentally manipulated. In cell culture models, oxidative stress (e.g., exposure to 40% ambient oxygen or low molecular weight iron) promotes lipofuscin accumulation, whereas growth at 8% oxygen and treatment with antioxidants or iron-chelators diminish it. Lipofuscin is a fluorochrome and may sensitize lysosomes to visible light, a process potentially important for the pathogenesis of age-related macular degeneration. Lipofuscin-associated iron sensitizes lysosomes to oxidative stress, jeopardizing lysosomal stability and causing apoptosis due to release of lysosomal contents. Lipofuscin accumulation may also diminish autophagocytotic capacity by acting as a sink for newly produced lysosomal enzymes and, therefore, interfere with recycling of cellular components. Lipofuscin, thus, may be much more directly related to cellular degeneration at old age than was hitherto believed.
Place, publisher, year, edition, pages
2002. Vol. 33, no 5, 611-619 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27703DOI: 10.1016/S0891-5849(02)00959-0Local ID: 12441OAI: oai:DiVA.org:liu-27703DiVA: diva2:248255