Abstract
Progressive telomere shortening with aging was studied using normal esophageal mucosal specimens from 177 human subjects aged between 0 and 102 years (yrs). We observed age-related shortening of the telomere, at a rate of 60 base pairs (bp) per year (yr). The mean telomere length of 12 neonates was 15.2 kilobase pairs (kbp) and that of 2 centenarians was 9.3 kbp. Mean (±SD) telomere lengths were 14.9±1.3, 14.0±1.8, 10.1±3.7, 10.4±3.3 and 9.5±3.1 kbp for the age groups less than 2 yrs, 2–20 yrs, 21–60 yrs, 61–80 yrs and 81–102 yrs, respectively. The variation in telomere length among individuals in the same age group was greater for the 3 older groups than for the 2 younger groups, as shown by the SDs. Furthermore, older individuals had greater telomere length variation than younger individuals, based on the lengths of DNA digested smears. Although the telomere length decreased significantly with aging at the rate of 60 bp per yr, differences in the mean telomere lengths between the 3 older age groups were not significant. Rapid shortening occurred in the young generations and there was no further substantial decrease in the esophageal mucosa after 60 yrs of age. Compared to the very rapid renewal rate of the esophageal epithelial cells, the annual reduction rate in telomere length was very low. These findings support the hypothesis that germ cells in the esophageal epithelium have a mechanism to lengthen telomeres.
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References
Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res., 37:614–636, 1965.
Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, and Allshire RC: Telomere reduction in human colorectal carcinoma and with ageing. Nature, 346: 866–868, 1990.
Blackburn EH: Structure and function of telomeres. Nature, 350: 569–573, 1991.
Levy MZ, Allsopp RC, Futcher AB, Greider CW, and Harley CB: Telomere end-replication problem and cell aging. J. Mol. Biol., 225: 951–960, 1992.
Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, and Wu J-R: A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA, 85: 6622–6626, 1988.
Harley CB, Futcher AB, and Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature, 345: 458–460, 1990.
Vaziri H, Schächter F, Uchida I, Wei L, Zhu X, Effros R, Cohen D, and Herley CB: Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet., 52: 661–667, 1993.
Lindsey J, McGill NI, Lindsey LA, Green DK, and Cooke HJ: In vivo loss of telomeric repeats with age in humans. Mutat. Res., 256: 45–48, 1991.
Hiyama E, Hiyama K, Tatsumoto N, Kodama T, Shay JW, and Yokoyama T: Telomerase activity in human intestine. Int. J. Oncol., 9: 453–458, 1996.
Nakamura K, Furugori E, Takubo K, Izumiyama N, Arai T, Esaki Y, Fujiwara M, Okayasu I, and Oshimura M: Telomere length in normal mucosa and cancer of the digestive tract. Tumor Markers (Shuyo Marker Kenkyukaishi), 14: 33–35, 1999. (in press) (in Japanese)
Chang E and Harley CB: Telomere length and replicative aging in human vascular tissues. Proc. Natl. Acad. Sci. USA, 92:11190–11194, 1995.
Takubo K, Nakamura K, Izumiyama N, Mafune K, Tanaka Y, Miyashita M, Sasajima K, Kato M, and Oshimura M: Telomerase activity in esophageal carcinoma. J. Surg. Oncol., 66: 88–92, 1997.
Greider CW: Telomere length regulation. Annu. Rev. Biochem., 65: 337–365,1996.
Eastwood GL: Gastrointestinal epithelial renewal. Gastroenterology, 72: 962–975, 1977.
Marques-Pereira JP and Leblond CP: Mitosis and differentiation in the stratified squamous epithelium of the rat esophagus. Am. J. Anat., 117: 73–90, 1965.
Greider CW and Blackburn EH: Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell, 43: 405–413, 1985.
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PLC, Coviello GM, Wright WE, Weinrich SL, and Shay JW: Specific association of human telomerase activity with immortal cells and cancer. Science, 266: 2011–2015, 1994.
Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, Yamamoto H, Ide T, and Utakoji T: Telomerase activity in normal human epithelial cells. Oncogene, 13: 433–439, 1996.
Hsiao R, Sharma HW, Ramakrishnan S, Keith E, and Narayanan R: Telomerase activity in normal human endothelial cells. Anticancer Res., 17: 827–832, 1997.
Counter CM, Gupta J, Harley CB, Leber B, and Bacchetti S: Telomerase activity in normal leukocytes and in hematologic malignancies. Blood, 85:2315–2320, 1995.
Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, Murakami Y, Kodama T, Piatyszek MA, Shay JW, and Matsuura Y: Telomerase activity in gastric cancer. Cancer Res., 55: 3258–3262, 1995.
Ikeguchi M and Kaibara S: Telomerase activity in esophageal squamous cell carcinoma and in normal esophageal epithelium adjacent to carcinoma. Jpn. J. Clin. Med. (Nipponrinsho), 56:1176–1180, 1998. (in Japanese with English abstract)
Morales CP, Lee EL, and Shay JW: In situ hybridization for the detection of telomerase RNA in the progression from Barrett’s esophagus to esophageal adenocarcinoma. Cancer, 83: 652–659, 1998.
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Takubo, K., Nakamura, KI., Izumiyama, N. et al. Telomere shortening with aging in human esophageal mucosa. AGE 22, 95–99 (1999). https://doi.org/10.1007/s11357-999-0011-6
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DOI: https://doi.org/10.1007/s11357-999-0011-6