telomere

telomere, segment of DNA occurring at the ends of chromosomes in eukaryotic cells (cells containing a clearly defined nucleus). Telomeres are made up of repeated segments of DNA that consist of the sequence 5′-TTAGGG-3′ (in which T, A, and G are the bases thymine, adenine, and guanine, respectively). Some human cells contain as many as 1,500 to 2,000 repeats of this sequence at each end of each chromosome. The number of repeats determines the maximum life span of a cell: each time a cell undergoes replication, multiple TTAGGG segments are lost. Once telomeres have been reduced to a certain size, the cell reaches a crisis point and is prevented from dividing further. As a consequence, the cell dies. Thus, the processes of cell aging and cell death are regulated in part by telomeres.

Telomeres are of special concern in the cellular mechanisms that underlie the development of some types of cancer. Telomeric control of cell life span appears to be inactivated by the expression of oncogenes (cancer-causing genes) or by the deactivation of tumour suppressor genes. In cells undergoing malignant transformation (progression to cancer), telomeres do shorten, but, as the crisis point nears, a formerly quiescent enzyme called telomerase becomes activated. This enzyme prevents the telomeres from shortening further and thereby prolongs the life of the cell.

Most malignant tumours—including breast cancer, colorectal cancer, prostate cancer, and ovarian cancer—exhibit telomerase activity. The more advanced the cancer, the greater the frequency of detectable telomerase in independent samples. Because cell immortality contributes to the growth of many cancers, telomerase is an attractive target for the development of new anticancer drugs.

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Telomeres also appear to be vulnerable to genetic factors that alter an organism’s rate of aging. For example, in humans, variations in a gene known as TERC (telomerase RNA [ribonucleic acid] component), which encodes an RNA segment of the telomerase enzyme, have been associated with reduced telomere length and an increased rate of biological aging. Persons who carry these variations are suspected to be several years older biologically compared with noncarriers who are the same chronological age. TERC mutations in combination with exposure to environmental factors, such as smoking and obesity, not only quicken the pace of biological aging but also increase a carrier’s susceptibility to age-related diseases, thereby resulting in the onset of those conditions relatively early in adult life.