Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults

Abstract

Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in 2 independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 -2002 (discovery set: n D 978, validation set: n D 531). We obtained DNA methylation profiles in whole blood samples by Illumina HumanMethylation450 BeadChip and calculated the FI according to the method of Mitnitski and Rockwood. Mixed linear regression models were implemented to assess the associations between smoking indicators and the FI. After controlling for potential covariates, current smoking, cumulative smoking exposure (pack-years), and time after smoking cessation (years) were significantly associated with the FI (P-value < 0.05). In the discovery panel, 17 out of 151 previously identified smoking-related CpG sites were associated with the FI after correction for multiple testing (FDR < 0.05). Nine of them survived in the validation phase and were designated as frailty-associated loci. A smoking index (SI) based on the 9 loci manifested a monotonic association with the FI. In conclusion, this study suggested that epigenetic alterations could play a role in smoking-associated development of frailty. The identified CpG sites have the potential to be prognostic biomarkers of frailty and frailty-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.

Quantitative Characterization of Biological Age and Frailty Based on Locomotor Activity Records

“…4A and 4B). Our findings regarding the impact of smoking are in concordance with the earlier results obtained by [39], where the Frailty Index -but not a linear predictor of chronological agesignificantly correlated with the regulation of smoking-associated methylation sites. We also showed that the BAA are significantly lower in individuals who had smoked early in life, but that the trend is reversed upon quitting smoking, presumably reducing the risks of future development of irreversible chronic health conditions.…”

Associations of self-reported smoking, cotinine levels and epigenetic smoking indicators with oxidative stress among older adults: a population-based study

“…In particular, detailed information on lifetime smoking history was acquired, including current smoking status and intensity, age at initiation and smoking intensities at various ages, as well as the age of quitting smoking for former smokers [28]. Additional information on body mass index (BMI) was extracted from a standardized form filled by the general practitioners during the health check-ups.…”

Biological age is a universal marker of aging, stress, and frailty

“…It is therefore expected that almost any method using organism state variables to predict chronological age, frailty, diseases or the remaining life expectancy should produce the more or less same predictors, albeit at a different signal to noise ratio. This is why biological age estimates are associated with both mortality (Christiansen et al 2016, Horvath et al 2015b, Marioni et al 2015 and morbidity risks (Horvath and Levine 2015, Horvath et al 2014a,b, 2015a, as well as with life-shortening lifestyles (Gao et al 2016) or diseases (Horvath and Levine 2015, Horvath et al 2014a, 2015a.…”