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Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

ABSTRACT: Leukocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11-year follow-up. Older mono- (MZ) and dizygotic (DZ) twin sisters (n = 386) participated in the study. Relative LTL was measured by qPCR at baseline. Physical functioning was measured by 6-min walking distance and level of physical activity (PA). Walking distance was measured at baseline and at 3-year follow-up. PA was assessed by questionnaire at baseline and at 3- and 11-year follow-ups. The baseline analysis was performed with path models, adjusted with age and within-pair dependence of twin pairs. The longitudinal analysis was performed with a repeated measures linear model adjusted for age and longitudinal within-pair dependence. A nonrandom missing data analysis was utilized. At baseline, in all individuals, LTL was associated with PA (est. 0.14, SE 0.06, p = 0.011), but not with walking distance. Over the follow-up, a borderline significant association was observed between LTL and walking distance (est. 0.14, SE 0.07, p = 0.060) and a significant association between LTL and PA (est. 0.19, SE 0.06, p = 0.001). The results suggest that LTL is associated with PA and may, therefore, serve as a biomarker predicting the development of disability. Longitudinal associations between LTL and PA were observed only when nonrandom data missingness was taken into account in the analysis.

SUBMITTER: Sillanpaa E

PROVIDER: S-EPMC5005900 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

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Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

Sillanpää Elina E Törmäkangas Timo T Rantanen Taina T Kaprio Jaakko J Sipilä Sarianna S

Age (Dordrecht, Netherlands) 20160304 2

Leukocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11-year follow-up. Older mono- (MZ) and dizygotic (DZ) twin sisters (n = 386) participated in the study. Relative LTL was measured by qPCR at baseline. Physi ...[more]

PMID: 26940017

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Project description:There is growing interest in elucidating the determinants of newborn telomere length, given its potential as a biomarker of lifetime disease risk affected by prenatal exposures. There is limited evidence that increased maternal stress during pregnancy predicts shorter newborn telomere length. However, the few studies published to date have been conducted primarily with small samples utilizing inconsistent definitions of maternal stress. Moreover, the potential influence of fetal sex as a moderator of maternal stress effects on newborn telomere length has been largely ignored despite compelling evidence of likely impact. In a prospective cohort study of pregnant women seeking routine prenatal care, we tested whether a range of maternal measures of stressor exposures, subjective feelings of stress, and mental health (depression, anxiety) were associated with newborn telomere length assessed from cord blood among 146 pregnant women and their newborn infants. We further examined whether the pattern of associations differed by infant sex. Sociodemographic and maternal and newborn health indicators were considered as potential covariates. When examined within the whole sample, none of the maternal psychosocial measures were associated with newborn telomere length. Among potential covariates, maternal history of smoking and preeclampsia in a previous pregnancy were negatively associated with newborn telomere length. In adjusted linear regression analyses that considered potential sex-specific effects, maternal depression, general anxiety, and pregnancy-specific anxiety symptoms were positively associated with newborn telomere length among males. Overall, the findings provide some evidence for an association between maternal psychosocial wellbeing in pregnancy and newborn telomere length in males, although in the opposite direction than previously reported. Maternal smoking and obstetric history prior to conception may be associated with shorter offspring telomere length.

Project description:BackgroundEpigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63-76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AAHorvath, AAGrimAge, respectively). Cox proportional hazard models were conducted for individuals and twin pairs.ResultsThe results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13-1.53) per one standard deviation (SD) increase in AAGrimAge. The results indicated no significant associations of AAHorvath with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02-2.20) per 1 SD increase in AAGrimAge. However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84-1.99). Similarly, in multivariable adjusted models the HR (1.42-1.49) was non-significant. In AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAge there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAge was associated with a higher all-cause mortality risk.ConclusionsIn conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.

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Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

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Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

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