Telomerase activity, telomere length and hTERT DNA methylation in peripheral blood mononuclear cells from monozygotic twins with discordant smoking habits

Abstract

Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA. Besides, the association between smoke and telomere length (TL) has been evaluated. Healthy monozygotic twins with discordant smoking habits were selected as study population to minimize inter-individual differences because of demographic characteristics and genetic heterogeneity. Statistically significant higher values of TA and TL were observed in smokers compared to nonsmoker co-twins. The multivariate analysis of data showed, besides smoking habits (P = 0.02), an influence of gender (P = 0.006) and BMI (P = 0.001) on TA and a borderline effect of gender (P = 0.05) on TL. DNA methylation analysis, focused on 100 CpG sites mapping in hTERT, highlighted nine CpG sites differentially methylated in smokers. When co-twins were contrasted, selecting as variables the intra-twin difference in TA and hTERT DNA methylation, a statistically significant inverse correlation (P = 0.003) was observed between TA and DNA methylation at the cg05521538 site. In conclusion, these results indicate an association of tobacco smoke with TA and TL and suggest a possible association between smoke-induced epigenetic effects and TA in healthy smokers. Environ. Mol. Mutagen. 58:551-559, 2017. © 2017 Wiley Periodicals, Inc.

Effect of alcohol use disorder on cellular aging

“…However, this is unlikely since BMI was not an independent predictor of TL in our regression analysis in HC or AUD participants. Similarly, while exposure to tobacco has been associated with TL (Marcon et al 2017) in our sample, Fagerstrom score was associated with AUD, but with TL only at a trend level (p < 0.1). Because we do not have data for past exposure to tobacco, we cannot rule out the possibility that the combination of heavy drinking and past smoke exposure might have contributed to shorter telomeres in AUD.…”

Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

“…A similar effect is observed in psychological stress in terms of OxS and TL, also showing lower telomerase activity [309]. Regarding smoking, there are contradictory results over the TL [310]; however, most studies suggest that there is a shortening of telomeres in smokers [311] associated with lipoperoxidation [312]. In addition, the consumption of sugary carbonated beverages is associated with shorter telomeres [313], even if the consumption starts from the early stages of life and before the development of obesity [314].…”

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

“…Of the 83 articles reviewed, 27 analyzed cigarette smoking and TL, all of which were observational studies (ethical reasons are crucial here explaining the lack of intervention studies). We grouped these observational studies in cross-sectional ( Table 4 ) [ 60 , 67 , 77 , 93 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ] and in case-control and longitudinal studies ( Table 5 ) [ 121 , 122 , 123 , 124 , 125 , 126 , 127 ]. There were 20 cross-sectional studies [ 60 , 67 , 77 , 93 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ], 2 case-control studies [ 124 , 127 ], and 5 longitudinal studies [ 121 , …”

“…On the other hand, contradictory findings were reported in a methylation and gene expression study carried out on twins. The authors observed greater telomerase activity and greater TL in smokers than in non-smokers [ 124 ].…”