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

The amount of the ageing pigment, lipofuscin, found in replicating cells de pends both on its rate of formation as well as its rate of dissolution by c ell division. We present a model which allows the calculation of the lipofu scin accumulation rate from measurements of its amount and of the cell cycl e duration. In two human fibroblast strains, the accumulation rate correlat es well with differences in oxidative stress/antioxidative defence as measu red by intracellular peroxide generation, protein carbonyl content, telomer e shortening rate and replicative life span. The lipofuscin content increas es with replicative age in both cultures. The rather steep increase in pres enescent fibroblasts is not solely due to a slowing down of the cell turnov er, but is partially caused by an increased rate of lipofuscin formation/ac cumulation. This might indicate an increased level of oxidative stress in p resenescent fibroblasts, or a decreased efficiency of proteolytic systems, or both. The results are in accordance with data demonstrating an adverse e ffect of lipofuscin accumulation on cellular protein turnover and suggest a n active role for lipofuscin accumulation in cellular senescence. (C) 2001 Elsevier Science Inc. All rights reserved.