Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

Sillanpää, Elina; Sipilä, Sarianna; Törmäkangas, Timo; Kaprio, Jaakko; Rantanen, Taina

doi:10.1093/gerona/glw178

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…The observed within-pair correlation in LTL among monozygotic twins pairs agree with earlier findings [ 9 , 22 ] suggesting strong effect of familial factors. In general, earlier studies have reported at most weak associations between LTL and physical function [ 23 , 24 ].…”

Section: Discussionsupporting

confidence: 92%

Biological clocks and physical functioning in monozygotic female twins

et al. 2018

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BackgroundBiomarkers of biological aging – DNA methylation age (DNAm age) and leukocyte telomere length (LTL)– correlate strongly with chronological age across the life course. It is, however, unclear how these measures of cellular wear and tear are associated with muscle strength and functional capacity, which are known to decline with older age and are associated with mortality. We investigated if DNAm age and LTL were associated with body composition and physical functioning by examining 48 monozygotic twin sisters.MethodsWhite blood cell DNAm age (predicted years) was calculated from Illumina 450 k BeadChip methylation data using an online calculator. DNAm age acceleration was defined from the residuals derived from a linear regression model of DNAm age on chronological age. LTL was measured by qPCR. Total body percentage of fat and lean mass were estimated using bioimpedance. Physical functioning was measured by grip strength, knee extension strength and by 10 m maximal walking speed test.ResultsIn all participants, DNAm age (58.4 ± 6.6) was lower than chronological age (61.3 ± 5.9 years). Pairwise correlations of monozygotic co-twins were high for DNAm age (0.88, 95% CI 0.79, 0.97), age acceleration (0.68, 95% CI 0.30, 0.85) and LTL (0.77, 95% CI 0.60, 0.94). Increased age acceleration i.e. faster epigenetic aging compared to chronological age was associated with lower grip strength (β = − 5.3 SE 1.9 p = 0.011), but not with other measures of physical functioning or body composition. LTL was not associated with body composition or physical functioning.ConclusionsTo conclude, accelerated DNAm age is associated with lower grip strength, a biomarker known to be associated with physiological aging, and which predicts decline in physical functioning and mortality. Further studies may clarify whether epigenetic aging explains the decline in muscle strength with aging or whether DNAm age just illustrates the progress of aging.Electronic supplementary materialThe online version of this article (10.1186/s12877-018-0775-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Biological clocks and physical functioning in monozygotic female twins

et al. 2018

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“…Research among adults suggests high heritability, with a large meta-analysis estimating telomere length heritability as 0.70 (Broer et al, 2013). However, many biological variables show increased heritability with advancing age (Sillanpaa et al, 2017), such that heritability of telomere length is likely lower among newborns than adults. Moreover, data suggest that telomere dynamics during early development are largely determinative of relative telomere length for life and that experiential/environmental factors have major impact on telomere length at birth (Hjelmborg et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Maternal cortisol output in pregnancy and newborn telomere length: Evidence for sex-specific effects

Enlow

Sideridis

Bollati

et al. 2019

Psychoneuroendocrinology

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Newborn telomere length is a potential biomarker of the effects of maternal-fetal processes on offspring long-term health. A number of maternal psychosocial and environmental factors in pregnancy (e.g., stress, health, socioeconomic status) have been associated with shortened telomere length at birth. The physiological mechanisms responsible for potential effects of maternal factors on newborn telomere length have yet to be identified. Indirect evidence suggests that disruptions in maternal hypothalamic-pituitary-adrenal (HPA) axis functioning in pregnancy may be involved. Studies are needed that test whether maternal HPA axis functioning in pregnancy

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“…Additionally, Zhang’s DNAmRiskScore, which was calculated based on 10 CpG sites [ 21 ], was shown to be strongly associated with all-cause mortality [ 21 ]. The relationship between TL and lung function has been reported to be positive or null [ 23 , 24 ]. Meanwhile, mtDNA-CN reduction is associated with chronic obstructive pulmonary disease [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of aging and lung function in the normative aging study

Wang

Just

Heiss

et al. 2020

Aging

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Elderly individuals who are never smokers but have the same height and chronological age can have substantial differences in lung function. The underlying biological mechanisms are unclear. To evaluate the associations of different biomarkers of aging (BoA) and lung function, we performed a repeated-measures analysis in the Normative Aging Study using linear mixed-effect models. We generated GrimAgeAccel, PhenoAgeAccel, extrinsic and intrinsic epigenetic age acceleration using a publically available online calculator. We calculated Zhang’s DNAmRiskScore based on 10 CpGs. We measured telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) using quantitative real-time polymerase chain reaction. A pulmonary function test was performed measuring forced expiratory volume in 1 second / forced vital capacity (FEV 1 /FVC), FEV 1 , and maximum mid-expiratory flow (MMEF). Epigenetic-based BoA were associated with lower lung function. For example, a one-year increase in GrimAgeAccel was associated with a 13.64 mL [95% confidence interval (CI), 5.11 to 22.16] decline in FEV 1 ; a 0.2 increase in Zhang’s DNAmRiskScore was associated with a 0.009 L/s (0.005 to 0.013) reduction in MMEF. No association was found between TL/mtDNA-CN and lung function. Overall, this paper shows that epigenetics might be a potential mechanism underlying pulmonary dysfunction in the elderly.

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Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

Cited by 8 publications

References 38 publications

Biological clocks and physical functioning in monozygotic female twins

Biological clocks and physical functioning in monozygotic female twins

Maternal cortisol output in pregnancy and newborn telomere length: Evidence for sex-specific effects

Biomarkers of aging and lung function in the normative aging study

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