Centrophenoxine Slows Down, but Does Not Reverse, Lipofuscin Accumulation in Cultured Cells

Abstract

Centrophenoxine, a drug used in the treatment of senile dementia, has been suggested to retard, or even reverse, lipofuscin accumulation within postmitotic cells. However, a true capacity of centrophenoxine to eliminate already formed lipofuscin inclusions has not been convincingly demonstrated. Moreover, no evidence has been obtained regarding the possible mechanisms through which intracellular content of lipofuscin would be diminished by centrophenoxine. Here we show that (a) centrophenoxine at concentrations of 0.25 or 0.5 mM diminishes lipofuscin accumulation within cultured neonatal rat cardiac myocytes (by 44% or 51%, respectively, during a period of 2 weeks) when it was constantly present in the culture medium; (b) the same treatment of rat cardiac myocytes and AG-1518 human f ibroblasts, however, does not eliminate already formed lipofuscin inclusions; (c) the formation of autophagic vacuoles, and ensuing degradation of their contents, are not influenced by centrophenoxine. Thus, our results do no...