Sowing the seeds of cancer: telomeres and age-associated tumorigenesis.

PURPOSE OF REVIEW

Advances in the health system and medical sciences are continuously pushing the barrier of life-expectancy. As a consequence, humans are being increasingly afflicted by age-associated diseases, such as cancer. The challenge now lies in understanding the mechanisms underlying ageing in order to reduce the lifetime risk for cancer.

RECENT FINDINGS

In long-lived mammals, telomere length and restriction of telomerase activity are important barriers preventing the uncontrolled cell division. Absence of telomerase dictates the continuous telomere erosion with each cell division, thus restraining the proliferation of incipient tumour cells. However, recent findings have revealed the unintended consequences of telomere control of cell division. Cells with short telomeres accumulate in older individuals increasing the risk of telomere depletion. Loss of telomere protection results in tetraploidization and genomic instability characteristic of epithelial cancers. Additionally, telomere shortening blocks cell proliferation and induces cell senescence. Senescent cells secrete proinflammatory factors and reactive oxygen species that increase the likelihood of cellular transformation and create the perfect soil for cancer development.

SUMMARY

Telomere shortening thus provides an example of antagonist pleiotropy, in which a beneficial characteristic that acts during the reproductive years of an organism may, later in life, contain the seed to its demise.