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
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