Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study
Yan Xu, Chuang Bo Xie, Jing Yang, Yong Ji Xing, Wei Ping Xia, Yang Liu, Wen Bin Xi, Zhao Ju Li, Wei Feng Tu, Jun Long Zhang
Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly.
The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex；difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5′end or 3′end of TERC was detected. We recruited 100 patients of elective surgery.
We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5′ end or 3′ end of TERC was not found.
These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.
1 A. Mézière, E. Paillaud, B. Plaud Anesthesia in the elderly La Presse Médicale., 42 (2013), pp. 197-201
2 M.R.K. Spanjer, N.A. Bakker, A.R. Absalom Pharmacology in the elderly and newer anaesthesia drugs Best Pract Res Clin Anaesthesiol., 25 (2011), pp. 355-365
3 N. Srinivas, S. Rachakonda, R. Kumar Telomeres and Telomere Length: A General Overview Cancers, 12 (2020), pp. 1-30
4 AG Young The role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing Philos Trans R Soc Lond B Biol Sci., 373 (2018), pp. 1-12
5 Y. Doksani The Response to DNA Damage at Telomeric Repeats and Its Consequences for Telomere Function Genes., 10 (2019), pp. 1-17
6 RM Cawthon Telomere measurement by quantitative PCR Nucleic Acids Res., 30 (2002), pp. 1-6
7 A. Vasilishina, A. Kropotov, I. Spivak, et al. Relative Human Telomere Length Quantification by Real-Time PCR Methods Mol Biol., 1896 (2019), pp. 39-44
8 HY Du, E Pumbo, J. Ivanovich, et al. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements Blood, 113 (2009), pp. 309-316
9 M. Herrmann, I. Pusceddu, W. März, et al. Telomere biology and age-related diseases Clin Chem Lab Med., 56 (2018), pp. 1210-1222
10 XJ Bai Biomarkes of aging Adv Exp Med Biol., 1086 (2018), pp. 217-234
11 L. Rode, B.G. Nordestgaard, S.E. Bojesen Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population J Natl Cancer Inst., 107 (2015), pp. 1-8
12 M.S. Rocca, C. Foresta, A. Ferlin Telomere length: lights and shadows on their role in human reproduction Biol Reprod., 100 (2019), pp. 305-317
13 JW Shay Telomeres and aging Curr Opin Cell Biol., 52 (2018), pp. 1-7
14 H. Adwan Shekhidem, L. Sharvit, E. Leman, et al. Telomeres and Longevity: A Cause or an Effect? Int J Mol Sci., 20 (2019), pp. 1-12
15 G. Saretzki Telomeres, Telomerase and Ageing Subcell Biochem., 90 (2018), pp. 221-308
16 X. Yuan, M. Kronström, M.L. Hellenius, et al. Longitudinal changes in leukocyte telomere length and mortality in elderly Swedish men Aging, 10 (2018), pp. 3005-3016
17 M. Olmos, JA Ballester, M.A. Vidarte, et al. The Combined Effect of Age and Premedication on the Propofol Requirements for Induction by Target-Controlled Infusion Anesth Analg, 90 (2000), pp. 1157-1161
18 X. Gao, Y. Zhang, U. Mons, et al. Leukocyte telomere length and epigenetic-based mortality risk score: associations with all-cause mortality among older adults Epigenetics, 13 (2018), pp. 846-857
19 S.G. Dean, C. Zhang, J. Gao, et al. The association between telomere length and mortality in Bangladesh Aging, 9 (2017), pp. 1537-1548
20 L. Smith, C. Luchini, J. Demurtas, et al. Telomere length and health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies Ageing Res Rev, 51 (2019), pp. 1-10
21 J. Helby, B.G. Nordestgaard, T. Benfield, et al. Shorter leukocyte telomere length is associated with higher risk of infections: a prospective study of 75,309 individuals from the general population Haematologica, 102 (2017), pp. 1457-1465
22 S. Eugene, T. Bourgeron, Z. Xu Effects of initial telomere length distribution on senescence onset and heterogeneity J Theor Biol, 413 (2017), pp. 58-65