Lipofuscin accumulation in proliferating fibroblasts in vitro: an indicator of oxidative stress

The amount of the ageing pigment, lipofuscin, found in replicating cells depends both on its rate of formation as well as its rate of dissolution by cell division. We present a model which allows the calculation of the lipofuscin accumulation rate from measurements of its amount and of the cell cycle duration. In two human fibroblast strains, the accumulation rate correlates well with differences in oxidative stress/antioxidative defence as measured by intracellular peroxide generation, protein carbonyl content, telomere shortening rate and replicative life span. The lipofuscin content increases with replicative age in both cultures. The rather steep increase in presenescent fibroblasts is not solely due to a slowing down of the cell turnover, but is partially caused by an increased rate of lipofuscin formation/accumulation. This might indicate an increased level of oxidative stress in presenescent fibroblasts, or a decreased efficiency of proteolytic systems, or both. The results are in accordance with data demonstrating an adverse effect of lipofuscin accumulation on cellular protein turnover and suggest an active role for lipofuscin accumulation in cellular senescence. (C) 2001 Elsevier Science Inc. All rights reserved.