Довжина теломер у мешканців Львівської області

  • Н. Л. Гулеюк
  • М. Тирка

Анотація

Aim. Telomeres are short, tandem repeats of DNA that cap linear chromosome ends by binding members of the shelterin protein complex to form protective telomere loops. An insufficient number of telomere repeats leads to chromosome uncapping, cell senescence, and death. Aim of this thesis is the analysis of relative telomere length (RTL) in whole blood among residents of Lviv region. Methods. The RTL in the whole blood cells was measured in 86 residents of various age (47 men and 39 women aged 18–72) using quantitative real-time PCR (Cawthon’s method). It is based on the simultaneous amplification of telomeric repeats (T) and a single copy gene (S). Results. There is a tendency to decrease RTL with age. The low correlation between RTL and age can be linked to various factors, including the heterogeneity of telomere length at birth, chronic socioeconomic stress, genetic determinism, sensitivity to exogenous pressures. Women and men did not differ significantly in the rate of RTL shortening. Conclusions. The results indicate the absence of reliable differences relative telomere length in individuals of different sexes. The low correlation between RTL and age can be linked to various factors, including insufficient sample size of people aged over 50 years. So in the future we plan to continue these studies in older people.

Keywords: relative telomere length, RT-PCR, age, gender.

Посилання

Griffith J.D., Comeau L., Rosenfield S., Stansel R.M., Bianchi A., Moss H., de Lange T. Mammalian telomeres end in a large duplex loop. Cell. 1999. V. 97. P. 503-514. doi: 10.1016/S0092-8674(00)80760-6

De Lange T. Protection of mammalian telomeres. Oncogene. 2002. V. 21. P. 532-540. doi: 10.1038/sj.onc.1205080

De Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes. Dev. 2005. V. 19. P. 2100-2110. doi: 10.1101/gad.1346005

Cairney C.J., Keith W.N. Telomerase redefined: integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. Biochimie. 2008. V. 90. P. 13-23. doi: 10.1016/j.biochi.2007.07.025

Zhao Y., Sfeir A.J., Zou Y., Buseman C.M., Chow T.T., Shay J.W., Wright W.E. Telomere extension occurs at most chromosome ends and is uncoupled from fill-in in human cancer cells. Cell. 2009. V. 138. P. 463-475. doi: 10.1016/j.cell.2009.05.026

Watson J.D. Origin of concatemeric T7 DNA. Nat. Newiol. 1972. V. 239 (94). P. 197-201. doi: 10.1038/newbio239197a0

Sfeir A.J., Chai W., Shay J.W., Wright W.E. Telomere-end processing the terminal nucleotides of human chromosomes. Mol. Cell. 2005. V. 18 (1). Р. 131-138. doi: 10.1016/j.molcel.2005.02.035

Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell. Res. 1965. V. 37. P. 614-636. doi: 10.1016/0014-4827(65)90211-9

Bischoff C., Graakjaer J., Petersen H.C., Jeune B., Bohr V.A, Koelvraa S., Christensen K. Telomere length among the elderly and oldest-old. Twin Res. Hum. Genet. 2005 - V. 8 (5). Р. 425-432. doi: 10.1375/twin.8.5.425

Blasco M.A. Telomeres and human disease: ageing, cancer and beyond. Nat. Rev. Genet. 2005. V. 6 (8). Р. 611-622. doi: 10.1038/nrg1656

Wong J.M., Collins K. Telomere maintenance and disease. Lancet. 2003. V. 362 (9388). P. 98-108. doi: 10.1016/S0140-6736(03)14369-3

Wright W.E., Shay J.W. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nat. Med. 2000. V. 6 (8). P. 849-851. doi: 10.1038/78592

Nordfjall K., Eliasson M., Stegmayr B., Lundin S., Roos G., Nilsson P.M. Increased abdominal obesity, adverse psychosocial factors and shorter telomere length in subjects reporting early ageing; the MONICA Northern Sweden Study. Scand. J. Public. Health. 2008. V. 36. P. 744-752. doi: 10.1177/1403494808090634

Bekaert S., Rietzschel E.R., De Buyzere M.L., De Bacquer D., Langlois M., Segers P., Cooman L., Van Damme P., Cassiman P., Van Criekinge W., Verdonck P., De Backer G.G., Gillebert T.C., Van Oostveldt P. Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease. Aging. Cell. 2007. V. 6. P. 639-647. doi: 10.1111/j.1474-9726.2007.00321.x

Gardner M., Bann D., Wiley L., Cooper R., Hardy R., Nitsch D., Martin-Ruiz C., Shiels P., Sayer A.A., Barbieri M., Bekaert S., Bischoff C., Brooks-Wilson A., Chen W., Cooper C., Christensen K., De Meyer T., Deary I., Der G., Diez Roux A., Fitzpatrick A., Hajat A., Halaschek-Wiener J., Harris S., Hunt S.C., Jagger C., Jeon H.S., Kaplan R., Kimura M., Lansdorp P., Li C., Maeda T., Mangino M., Nawrot T.S., Nilsson P., Nordfjall K., Paolisso G., Ren F., Riabowol K., Robertson T., Roos G., Staessen J.A., Spector T., Tang N., Unryn B., van der Harst P., Woo J., Xing C., Yadegarfar M.E., Park J.Y., Young N., Kuh D., von Zglinicki T., Ben-Shlomo Y. Gender and telomere length: Systematic review and meta-analysis. Exp. Gerontol. 2014. V. 51. P. 15-27. doi: 10.1016/j.exger.2013.12.004

Cherkas L.F., Hunkin J.L., Kato B.S., Richards J.B., Gardner J.P., Surdulescu G.L., Kimura M., Lu X., Spector T.D., Aviv A. The association between physical activity in leisure time and leukocyte telomere length. Arch. Intern. Med. 2008. V. 168. P. 154-158. doi: 10.1001/archinternmed.2007.39

Epel E.S., Blackburn E.H., Lin F., Dhabhar F.S., Adler N.E., Morrow J.D., Cawthon R.M. Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. USA. 2004. V. 101. P. 17312-17315. doi: 10.1073/pnas.0407162101

Valdes A.M., Andrew T., Gardner J.P., Kimura M., Oelsner E., Cherkas L.F., Aviv A., Spector T.D. Obesity, cigarette smoking, and telomere length in women. Lancet. 2005. V. 366. P. 662-664. doi: 10.1016/S0140-6736(05)66630-5

Cawthon R.M., Smith K.R., O'Brien E., Sivatchenko A., Kerber R.A. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet. 2003. V. 361. P. 393-395. doi: 10.1016/S0140-6736(03)12384-7

Hunt S.C., Chen W., Gardner J.P., Kimura M., Srinivasan S.R., Eckfeldt J.H., Berenson G.S., Aviv A. Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study. Aging. Cell. 2008. V. 7. P. 451-458. doi: 10.1111/j.1474-9726.2008.00397.x

von Zglinicki T. Will your telomeres tell your future?. BMJ. 2012. V. 344. P. 1727. doi: 10.1136/bmj.e1727

Dan T.A., Klelia D.S., Kuzawa C.W., Hayes M.G., Humphries S.E. Substantial variation in qPCR measured mean blood telomere lengths in young men from eleven European countries. Am. J. Hum. Biol. 2011. V. 23. P. 228-231. doi: 10.1002/ajhb.21126

Canela A., Vera E., Klatt P., Blasco M.A. High-throughput telomere length quantification by FISH and its application to human population studies. Proc. Natl Acad. Sci. USA. 2007. V. 104, № 13. Р. 5300-5305. doi: 10.1073/pnas.0609367104

Krasnenkov D.S., Koliada A.K., Akhaladze N.G., Kukharskiy V.M., Potalitsin P.Iu., Kholod O.V., Kokhichko E.V., Vayserman A.M. Dlina telomer v kletkakh krovi u zhiteley Kievskoy oblasti raznogo vozrasta. Probl. stareniia i dolgoletiia. 2014. V. 23 (3). P. 254-261. [in Russian]

Koliada A.K., Vayserman A.M., Krasnenkov D.S., Karaban' I.N. Issledovanie dliny telomer u patsientov s bolezn'iu Parkinsona. Zhurnal Nevrologii i psikhiatrii. 2014. V. 8. P. 59-62. [in Russian]

Makukh H.V., Zastavna D.V., Tyrkus M.Ya., Tretiak B.I., Chorna L.B. Sposib vydilennia DNK z leykotsytiv peryferiynoi krovi. Pat. 32044 UA, MPK G01N33/49 (2006.01) zaiavnyk DU «Instytut spadkovoi patolohii AMNU». No u200801896; zaiav. 14.02.2008; opubl. 25.04.2008, Biul. No. 8. [in Ukrainian]

Maniatis T., Friz E., Sembruk Zh. Molekuliarnoe klonirovanie.Moskva: Mir, 1985. 420 p. [in Russian]

Cawthon R.М. Telomere measurement by quantitative PCR. Nucl Acids Res. 2002. V. 30. e 47. doi: 10.1093/nar/30.10.e47

Bekaert S., Derradji H., Baatout S. Telomere biology in mammalian germ cells and during development. Dev Biol. 2004. V. 274(1). P. 15-30. doi: 10.1016/j.ydbio.2004.06.023

Diez Roux A.V., Ranjit N., Jenny N.S., Shea S., Cushman M., Fitzpatrick A., Seeman T. Race/ethnicity and telomere length in the Multi-Ethnic Study of Atherosclerosis. Aging Cell. 2009. V. 8(3). P. 251-257. doi: 10.1111/j.1474-9726.2009.00470.x