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2002, Number S1

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Gac Med Mex 2002; 138 (S1)

Telomeres, Aging, and Tumorigenesis

Shay JW

Language: English
References: 27
Page: 2-3
PDF size: 29.34 Kb.


Text Extraction

Telomeres are the repetitive DNA sequences at the end of all linear chromosomes. In humans, there are 46 chromosomes and thus 92 telomere ends that consist of thousands of repeats of the six nucleotide sequence, TTAGGG. The telomere-telomerase hypothesis of aging and cancer is based on findings that most human tumors have telomerase activity while normal human somatic cells do not. Telomere length is maintained by a balance between processes that lengthen telomeres (telomerase) and processes that shorten telomeres (the end-replication problem). Telomerase (TEE-LOM-ER-ACE) is a ribonucleoprotein enzyme complex (a cellular reverse transcriptase) that has been referred to as a cellular immortalizing enzyme, which stabilizes telomere length by adding hexameric (TTAGGG) repeats onto the telomeric ends of the chromosomes, thus compensating for continued erosion of telomeres that occurs in its absence. The enzyme is expressed in adult reproductive cells, but is undetectable in normal somatic cells except for proliferative cells of renewal tissues (e.g., bone marrow cells, basal cells of the epidermis, proliferative endometrium, and intestinal crypt cells). In all dividing telomerase silent somatic cells and in nearly all dividing telomerase competent stem cells, progressive telomere shortening is observed, eventually leading to greatly shortened telomeres and to a limited ability to continue to divide. It has been proposed that telomere shortening may be a molecular clock mechanism that counts the number of times a cell has divided and when telomeres are short, cellular senescence (growth arrest) occurs. It is believed that shortened telomeres in mitotic (dividing) cells may be responsible for some of the changes we associate with normal aging.


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