T. Kurz

An inverse correlation between lifespan and lipofuscin (LF) accumulation within postmitotic cells such as neurons and myocardial cells has been clearly shown. LF accumulation inside lysosomes affects the renewal of the cell components by autophagy. Therefore, it can be assumed that diminished LF accumulation would delay aging. LF forms intralysosomally secondary to iron-catalyzed peroxidation. Reduction of intralysosomal redox-active iron levels should therefore reduce LF formation. We have recently shown that apo-ferritin, metallothionein and heat shock protein 70 following autophagy temporarily bind intralysosomal iron and prevent intralysosomal oxidative stress. In the postmitotic retinal pigment epithelial (RPE) cells, heavy LF accumulation is associated with age-related macular degeneration (AMD). Initially, RPE cells disappear and secondarily the photoreceptors as well. Exposure to blue light that enhances oxidation is known to aggravate macular degeneration, while zinc intake has been seen to delay the disease. Interestingly, zinc exposure upregulates metallothionein that binds a variety of metals, including iron. As a result cells become more resistant to lysosomal permeabilization that is a severe effect of intralysosomal oxidative stress. Presumably, LF accumulation which is an effect of less drastic stress would also be diminished.

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Oxidative stress