Energy metabolism in cultured human fibroblasts during aging in vitro

To explore the relationship between energy metabolism and the limited replicative life span of cultured human fibroblasts, we studied several bioenergetic parameters in normal fibroblasts at early passage (young cells) and at late passage (old cells) and early passage cells from a subject with the Hutchinson-Gilford (progeria) syndrome. Old cells consumed more glucose and produced more lactate during growth, but O2 consumption, both basal and following maximum uncoupling of oxidative phosphorylation by SF-6847, was the same as in young cells. Progeria cells produced the most lactate but did not consume more glucose, while their basal and uncoupled O2 consumption was similar to that of young and old cells during both log and confluent states. Consumption of glutamine, a source of both oxidative energy and lactate, was approximately the same in all three cell types as was 14CO2 production from 2- 14C-pyruvate and 5- 14C-glutamate. ATP and ADP concentrations were similar in all cell types with a rise in the ATP/ADP ratio during growth from log to confluent state. Thus, old and progeria cells, in contrast to young cells, produce more lactate during growth consistent with a rise in energy demand and/or inefficiency of oxidative phosphorylation. Although limitations in total energy output do not appear to be causal to the loss of replicative capacity in normal cells after serial passage, they could play a role in the curtailed replicative capacity of progeria cells.