Lipofuscin accumulation and ageing of fibroblasts

Lipofuscin accumulates in postmitotic cells. In human fibroblasts, accumulation of lipofuscin as measured by cellular autofluorescence is exponential at first, but stops at a certain level. At the same time, cell death starts to decrease cell numbers significantly. Artificial lipofuscin-like material can be prepared by UV-crosslinking of mitochondrial preparations. This material is easily phagocytosed by human fibroblasts and results in an increased cellular lipofuscin accumulation. Such a forced lipofuscin accumulation is sufficient to block cellular proliferation within a short time and to induce cell death as soon as the cellular lipofuscin autofluorescence reaches the same upper limit as 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.