The Association Between Telomere Length and Propofol Dose in Anesthesia-induction

Summary

Telomeres are protein-bound DNA repeat structures at the end of eukaryotic chromosomes that are made up of a simple repetitive sequence (in humans, TTAGGG) and regulate cellular replicative capacity and cellular proliferation, protect chromosomes from fusing together during mitosis and maintain genomic stability, and prevent the loss of genetic data. Telomeres are specialized repetitive DNA sequences, typically ranging from 5,000 to 15,000 bp in humans, which are the critical chromosome capping DNA sequences. The loss of telomere repeats diminishes telomeric functional capacity.Telomere length(TL) is important in determining telomere function.This is known as the end replication problem and results in a gradual decline in TL over time. Consequently,leukocyte TL shortens in a predictable way with age by roughly 20-40 base pairs per year. Cellular senescence and subsequent cell death often occur when the mean telomere length reaches a critical value.Shortened telomeres and lower telomerase are linked to age-related risk factors and disease.Peripheral blood leukocyte express telomerase at low levels, which can be measured over a short duration (hours) to demonstrate immediate, short-term changes. Shorter mean leukocyte telomere length has been shown to be associated with risk of several age-related diseases.The dosage of propofol gradually reduced with the aging process. However,it is not known whether the telomere length and variation of telomerase in PBL relate to the dosage of propofol and time of consciousness disappearance in anesthesia induction. In this exploratory study, the investigators examined that the changes of peripheral blood leukocyte telomere length was associated with the dosage of propofol and time of consciousness disappearance in anesthesia induction. Given the importance of telomeres in nuclear and cellular function, the central role of telomere length in determining telomere function,the investigator study that the changes of telomere length in peripheral blood leukocyte of patients are associated with the dosage of propofol in anesthesia induction.

Timeline

Start

2017-12-01

Primary completion

2018-02-01

Completion

2018-02-28

Publications

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• Background Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008 Apr;88(2):557-79. doi: 10.1152/physrev.00026.2007.
• Background Biegler KA, Anderson AK, Wenzel LB, Osann K, Nelson EL. Longitudinal change in telomere length and the chronic stress response in a randomized pilot biobehavioral clinical study: implications for cancer prevention. Cancer Prev Res (Phila). 2012 Oct;5(10):1173-82. doi: 10.1158/1940-6207.CAPR-12-0008. Epub 2012 Jul 24.
• Background Starkweather AR, Alhaeeri AA, Montpetit A, Brumelle J, Filler K, Montpetit M, Mohanraj L, Lyon DE, Jackson-Cook CK. An integrative review of factors associated with telomere length and implications for biobehavioral research. Nurs Res. 2014 Jan-Feb;63(1):36-50. doi: 10.1097/NNR.0000000000000009.
• Background Munoz P, Blanco R, Blasco MA. Role of the TRF2 telomeric protein in cancer and ageing. Cell Cycle. 2006 Apr;5(7):718-21. doi: 10.4161/cc.5.7.2636. Epub 2006 Apr 1.
• Background Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, Beveridge AJ, Rafelt S, Moore J, Nelson C, Soranzo N, Zhai G, Valdes AM, Blackburn H, Mateo Leach I, de Boer RA, Kimura M, Aviv A; Wellcome Trust Case Control Consortium; Goodall AH, Ouwehand W, van Veldhuisen DJ, van Gilst WH, Navis G, Burton PR, Tobin MD, Hall AS, Thompson JR, Spector T, Samani NJ. Common variants near TERC are associated with mean telomere length. Nat Genet. 2010 Mar;42(3):197-9. doi: 10.1038/ng.532. Epub 2010 Feb 7.
• Background Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet. 2010 May;11(5):319-30. doi: 10.1038/nrg2763. Epub 2010 Mar 30.
• Background Capezzone M, Cantara S, Marchisotta S, Filetti S, De Santi MM, Rossi B, Ronga G, Durante C, Pacini F. Short telomeres, telomerase reverse transcriptase gene amplification, and increased telomerase activity in the blood of familial papillary thyroid cancer patients. J Clin Endocrinol Metab. 2008 Oct;93(10):3950-7. doi: 10.1210/jc.2008-0372. Epub 2008 Jul 29.
• Background Epel ES, Lin J, Dhabhar FS, Wolkowitz OM, Puterman E, Karan L, Blackburn EH. Dynamics of telomerase activity in response to acute psychological stress. Brain Behav Immun. 2010 May;24(4):531-9. doi: 10.1016/j.bbi.2009.11.018. Epub 2009 Dec 16.
• Background Humphreys J, Epel ES, Cooper BA, Lin J, Blackburn EH, Lee KA. Telomere shortening in formerly abused and never abused women. Biol Res Nurs. 2012 Apr;14(2):115-23. doi: 10.1177/1099800411398479. Epub 2011 Mar 8.

Drugs

Indications

No indication recorded.