Fibroblast cultures from healthy centenarians have an active proteasome

Healthy centenarians represent the best example of successful ageing. Vario us studies have shown that centenarians have escaped the major age-associat ed diseases, they have several well-conserved immune parameters and at leas t one gene allele has been identified and linked with their increased longe vity. During ageing there is an accumulation of oxidised proteins, a phenom enon that has been related to an impaired function of the 20S proteasome in aged cells. We have, therefore, analysed the expression and the proteolyti c activity of the proteasome in centenarian cells. Four fibroblast cultures derived from healthy centenarians were studied and compared with cultures derived from adult donors of different ages. Analysis of several proteasome subunits RNA expression levels, determination of one peptidase activity an d identification of oxidised proteins in these samples revealed that centen arian cultures have a functional proteasome. In addition, it was found that the centenarian cultures exhibit characteristics similar to the younger ra ther than the older control donors derived cultures in all three assays. Th ese data indicate that centenarian cells may be different from elderly dono rs cells, thus opening up new dimensions for the identification and charact erisation of factors that are linked with longevity. (C) 2000 Elsevier Scie nce Inc. All rights reserved.