Influence of aging and cell senescence on telomerase activity in keratinocytes

Telomeres, which exist in eukaryotic chromosome ends in specialized G-rich TTAGGG structure, protect the ends from degradation or fusion. On the other hand, telomerase is a ribonucleoprotein complex enzyme that synthesizes TT AGGG repeat sequences at the ends of eukaryotic chromosomes. Previous studi es suggested that telomere length and telomerase activity cooperate in agin g and immortalization of cells. Here, we examined telomere: length and telo merase activity in keratinocytes from seven human subjects, including a pat ient with Werner's syndrome. Telomere length in keratinocytes from healthy individuals was shortened with aging. However, telomerase activity from an individual aged 42 years was reduced, compared with that from a 0 year old individual. Passages of keratinocytes reduced telomerase activity significa ntly in F2 and F3 keratinocytes from 0 and 42 year old individuals. Withdra wal of either EGF or amphiregulin from medium resulted in down-regulation o f telomerase activity. These results suggest that telomere length and telom erase activity ill primary cultured keratinocytes may be one of the paramet ers for cell senescence. However, there remain obscure factors such as ultr aviolet-B radiation and growth factors. (C) 2000 Elsevier Science Ireland L td. All rights reserved.