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 TTAGGG repeat sequences at the ends of eukaryotic chromosomes. Previous studies suggested that telomere length and telomerase activity cooperate in aging and immortalization of cells. Here, we examined telomere length and telomerase activity in keratinocytes from seven human subjects, including a patient 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 significantly in F2 and F3 keratinocytes from 0 and 42 year old individuals. Withdrawal of either EGF or amphiregulin from medium resulted in down-regulation of telomerase activity. These results suggest that telomere length and telomerase activity in primary cultured keratinocytes may be one of the parameters for cell senescence. However, there remain obscure factors such as ultraviolet-B radiation and growth factors.