Telomere Length in Fibroblasts and Blood Cells from Healthy Centenarians

Abstract

Several lines of evidence indicate that telomere shortening duringin vitroaging of human somatic cells plays a causal role in cellular senescence. A critical telomere length seems to be associated with the replicative block characterizing senescent cells. In this paper we analyzed the mean length of the terminal restriction fragments (TRF) in fibroblast strains from 4 healthy centenarians, that is, in cells agedin vivo,and from 11 individuals of different ages. No correlation between mean TRF length and donor age was found. As expected, telomere shortening was detected duringin vitropropagation of centenarian fibroblasts, suggesting that in fibroblasts agedin vivotelomeres can be far from reaching a critical length. Accordingly, chromosome analysis did not show the presence of telomeric associations in early passage centenarian fibroblasts. In blood cells from various individuals, the expected inverse correlation between mean TRF length and donor age was found. In particular, a substantial difference (about 2 kb) between telomere length in the two cell types was observed in the same centenarian. Expression analysis of three senescence-induced genes, i.e., fibronectin, apolipoprotein J, and p21, revealed for only the fibronectin expression levels a clear positive correlation with donor age. Our results suggest that (1) telomere shortening could play a different role in the aging of different cell types and (2) the characteristics of fibroblasts agedin vitromight not be representative of what occursin vivo.