In vivo aging of human fibroblasts does not alter nuclear plasticity in heterokaryons

In vivo aging of human fibroblasts altered proliferative properties but not the potential for novel gene expression in response to muscle trans-acting factors. Heterokaryons produced by fusing fibroblasts with muscle cells permitted a dissociation of the effects of aging on cell division and other cell functions. Skin fibroblasts derived from fetal and adult stages of development were distinct cell types based on their doubling time, protein content, cell size, and specific binding of insulin and insulin-like growth factor I. Despite these differences in growth parameters, the two cell types were indistinguishable in heterokaryons. Muscle gene activation occurred in the absence of changes in chromatin structure requiring DNA replication. In addition, the time course, maximal efficiency, and effect of gene dosage on the expression of muscle gene products were similar for heterokaryons containing fetal and adult fibroblasts but distinct for heterokaryons containing keratinocytes. The difference between fibroblasts and keratinocytes in the time course of muscle gene expression is likely to reflect mechanisms of gene activation at the transcriptional level, since the kinetics of muscle protein accumulation paralleled that of muscle transcripts. These results indicate that nuclear plasticity is not altered in fibroblasts by in vivo aging.