Program in mammalian telomere biology

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The ends of mammalian chromosomes contain variable numbers of TTAGGG repeats. In many species this telomeric DNA is lost due to the end replication problem, as normal somatic cells replicate. When cells lose sufficient telomeric DNA, a DNA damage signal is generated, activating the ATM kinase and p53 transcription factor to block the cell cycle and induce cell replicative senescence. Senescence is thought to serve as a barrier to cell immortality and abnormal cell growth since it limits cell replicative capacity. However, short telomeres also result in genetic instability leading to a variety of diseases and large correlational studies have linked short telomeres to high rates of cell transformation. Short telomeres are also associated with early mortality, suggesting that telomere length might contribute to determining lifespan. Studies of monozygotic and dizygotic twins and elderly populations have yielded conflicting results, leaving the question of whether telomere length per se affects life span, controversial.