Influence of the energetic pattern of mitochondria in cell ageing.

Injections of mitochondria isolated from liver of young or old rats have been performed in young or old WI-38 human fibroblasts and the survival of the injected cells was followed with time. Cells having received young mitochondria behave as the control non-injected cells while cells having received old mitochondria showed signs of degeneration after a few days. Such a behaviour could however be obtained with young mitochondria when partially uncoupled. The negative effect of the presence of uncoupled mitochondria could be overcome by addition of a ketone body: D(-) beta-hydroxybutyrate. When comparisons were performed between injected young and old fibroblasts, old cells were found less efficient in counteracting the presence of uncoupled mitochondria. These results clearly indicate that old cells contain partly altered mitochondria which are less able to fulfil their energy requirement so that a general lowering of homeostasis but also an increased susceptibility, toward unfavorable situations is obtained.