Alternative pathways for the extension of cellular life span: inactivationof p53/pRb and expression of telomerase

Telomere shortening may be one of several factors that contribute to the on set of senescence in human cells, The p53 and pRb pathways are involved in the regulation of cell cycle progression from G1 into S phase and inactivat ion of these pathways leads to extension of life span, Short dysfunctional telomeres may be perceived as damaged DNA and may activate these pathways, leading to prolonged arrest in G1, typical of cells in senescence. Inactiva tion of the p53 and pRb pathways, however, does not lead to cell immortaliz ation, Cells that overcome senescence and have an extended life span contin ue to lose telomeric DNA and subsequently enter a second phase of growth ar rest termed 'crisis', Forced expression of telomerase in human cells leads to the elongation of telomeres and immortalization, The development of huma n cancer is frequently associated with the inactivation of the pRb and p53 pathways, attesting to the importance of senescence in restricting the tumo r-forming ability of human cells, Cancer cells must also maintain telomere length and, in the majority of cases, this is associated with expression of telomerase activity.