Telomeres and Aging

Geraldine Aubert and Peter M. Lansdorp, Telomeres and Aging, physical Rev 88: 557-579, 2008; doi:10.1152/physrev.00026.2007

Telomeres play a central role in cell fate and aging by adjusting the cellular response to stress and growth stimulation on the basis of previous cell divisions and DNA damage.

The average telomere length is set and maintained in cells of the hemline which typically express high levels of telomerase. In somatic cells, telomere length is very heterogeneous but typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age.

Aging can be defined as the progressive functional decline of tissue function that eventually results in mortality.

In laboratory mice, Baker’s yeast, mustard plants, and roundworms, complete loss of telomerase is tolerated for at least several generations. In contrast, a modest twofold reduction in telomerase levels in humans is now known to cause severe clinical symptoms including aplastic anemia, immune deficiencies, and pulmonary fibrosis after one to three generations.

While telomere loss may act as a tumor suppressor mechanism, it also promotes tumor growth by driving selection of cells with defective DNA damage response.

Telomeric DNA typically ends win a single-strand G-rich overhang of between 50 and 300 nucleotides at the 3′ end, which has been proposed to fold back onto duplex telomeric DNA forming a “T-loop” structure.

Human chromosome ends are typically capped with between 0.5 and 15 kilobase pairs of detectable telomere repeats depending on the type of tissue, the age of the donor, and the replicative history of the cells.

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