Recent advances in cellular senescence, cancer and aging

How much do we know about the biology of aging from cell culture studies? Most normal somatic cells have a finite potential to divide due to a process termed cellular or replicative senescence. A growing body of evidence suggests that senescence evolved to protect higher eukaryotes, particularly mammals, from developing cancer. We now know that telomere shortening, due to the biochemistry of DNA replication, induces replicative senescence in human cells. However, in rodent cells, replicative senescence occurs despite very long telomeres. Recent findings suggest that replicative senescence is just the tip of the iceberg of a more general process termed cellular senescence. It appears that cellular senescence is a response to potentially oncogenic insults, including oxidative damage. In young organisms, growth arrest by cell senescence suppresses tumor development, but later in life, due to the accumulation of senescent cells which secret factors that can disrupt tissues during aging, cellular senescence promotes tumorigenesis. Therefore, antagonistic pleiotropy may explain in part, if not in whole, the apparently paradoxical effects of cellular senescence, though this still remains an open question.