LIPOFUSCIN ACCUMULATION AND AGING OF FIBROBLASTS

Lipofuscin accumulates in postmitotic cells. In human fibroblasts, acc umulation of lipofuscin as measured by cellular autofluorescence is ex ponential at first, but stops at a certain level. At the same time, ce ll death starts to decrease cell numbers significantly. Artificial lip ofuscin-like material can be prepared by UV-crosslinking of mitochondr ial preparations. This material is easily phagocytosed by human fibrob lasts and results in an increased cellular lipofuscin accumulation. Su ch a forced lipofuscin accumulation is sufficient to block cellullar p roliferation within a short time and to induce cell death as soon as t he cellular lipofuscin autofluorescence reaches the same upper limit a s that observed in senescent cells. It is concluded that accumulation of lipofuscin in postmitotic cells is not just an innocent consequence of ageing, but rather one amongst the important causes of senescence.