Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length.
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ABSTRACT:
SUBMITTER: Dempsey PC
PROVIDER: S-EPMC9021230 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length.
Dempsey Paddy C PC Musicha Crispin C Rowlands Alex V AV Davies Melanie M Khunti Kamlesh K Razieh Cameron C Timmins Iain I Zaccardi Francesco F Codd Veryan V Nelson Christopher P CP Yates Tom T Samani Nilesh J NJ
Communications biology 20220420 1
Walking pace is a simple and functional form of movement and a strong predictor of health status, but the nature of its association with leucocyte telomere length (LTL) is unclear. Here we investigate whether walking pace is associated with LTL, which is causally associated with several chronic diseases and has been proposed as a marker of biological age. Analyses were conducted in 405,981 UK Biobank participants. We show that steady/average and brisk walkers had significantly longer LTL compare ...[more]
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Project description:Objective Hyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers. Methods A Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis. Results An inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; β=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels. Conclusions Serum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.
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Project description:BackgroundThe independent and additive associations of walking pace and grip strength on dementia risk and the potential modifying effects of age, APOE phenotypes, and other dementia risk factors on the walking pace and dementia relationships demand further clarification. We aimed to investigate the independent and additive relationships of walking pace and handgrip strength on the risk of new-onset dementia and examine the potentially modifying effects of age, APOE phenotypes, lifestyle factors, and family history of dementia in the relationships.MethodsA total of 495,700 participants from the UK Biobank, who were free of dementia at baseline, were included in this study. Walking pace was self-defined as slow, average, or brisk. Handgrip strength was assessed by dynamometer and was divided into sex-specific quartiles. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. Other dementia risk factors, including education, physical activity, hypertension, depression, diabetes, and family history of dementia, were also collected. The primary outcome was new-onset all-cause dementia.ResultsOver a median follow-up duration of 12.0 years, 3986 (0.8%) participants developed new-onset all-cause dementia. Compared with those with slow walking pace, participants with average (HR, 0.61; 95%CI: 0.55-0.68) or brisk (HR, 0.59; 95%CI: 0.52-0.67) walking pace had a significantly lower risk of new-onset all-cause dementia. Moreover, compared with those with both slow walking pace and lower handgrip strength (the first quartile), the lowest risk of new-onset all-cause dementia was observed in participants with both average or brisk walking pace and higher handgrip strength (the 2-4 quartiles) (HR, 0.45; 95%CI: 0.40-0.52). Notably, the negative relationship between walking pace and the risk of new-onset all-cause dementia was significantly reduced as APOE ε4 dosage increased (APOE ε4 dosages = 0 or 1: brisk vs. slow: HR, 0.55; 95%CI: 0.48-0.63; vs. APOE ε4 dosages = 2: brisk vs. slow: HR, 1.14; 95%CI: 0.77-1.68; P for interaction = 0.001) or age increased (< 58 [median]: brisk vs. slow: HR, 0.27; 95%CI: 0.18-0.41; vs. ≥ 58 years: brisk vs. slow: HR, 0.55; 95%CI: 0.48-0.63; P for interaction = 0.007).ConclusionsWalking pace was inversely associated with new-onset dementia in the general population, especially in younger participants and those with lower APOE ε4 dosage. Participants with both faster walking pace and higher handgrip strength had the lowest risk of dementia, suggesting that maintaining both high handgrip strength and fast walking pace may be a more comprehensive strategy for preventing dementia risk.
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Project description:PurposeTwo mechanisms implicated in telomere shortening are oxidative stress and inflammation, both of which are linked to bone and muscle loss suggesting a pathological link between telomere attrition and osteosarcopenia. Using older adults aged 60 years and over in the UK Biobank, we examined the association between leukocyte telomere length and osteosarcopenia.MethodsBaseline leukocyte telomere length was measured using a multiplex qPCR technique and expressed as the amount of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Osteosarcopenia data was from the first imaging visit and defined by WHO criteria (femoral neck bone density T score ≤ -1) for osteopenia/osteoporosis plus either the EWGSOP2 (low appendicular lean mass/height2 and low grip strength) or SDOC (low grip strength and slow walking pace) criteria for sarcopenia. Binary or multinomial logistic regression models were used to associate telomere length and osteosarcopenia or its components, adjusting for the covariates: age, sex, race, education, Townsend deprivation index, alcohol, smoking, BMI/weight, physical activity levels.ResultsAmong 20,400 older adults (mean age: 67.79 ± 4.9 years, 53% men), the prevalence of osteosarcopenia by EWGSOP2 (n = 96, 0.47%) or SDOC (n = 205, 1%) criteria was low at the first imaging visit (mean 8.82 years after baseline). Baseline telomere length was not associated with osteosarcopenia by EWGSOP2 (Relative Risk (RR): 1.00, 95% CI: 0.82-1.23 comparing osteosarcopenia to normal (non-osteopenic, non-osteoporotic, and non-sarcopenic) per Standard Deviation (SD) increase in telomere length) or SDOC (RR: 0.95, 95% CI: 0.83-1.09) criteria. Longer telomere length was associated with a lower risk of slow walking pace (Odds Ratio: 0.92, 95% CI: 0.87-0.99 per SD increase in telomere length, p = 0.021). Telomere length, however, was not associated with low grip strength, low bone density or low appendicular lean mass/height2 (p > 0.05).ConclusionsIn this population-based study, telomere length was not associated with osteosarcopenia; however, slow walking pace was. Further studies are needed to reexamine this relationship, including a greater number of the oldest-old (≥75 years) where osteosarcopenia is more prevalent.
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Project description:BackgroundThe individual and combined relations of handgrip strength and walking pace with the risk of chronic kidney disease (CKD) remain uncertain. We aimed to investigate the relationship of handgrip strength and/or walking pace with incident CKD, using data from the large-scale, observational UK Biobank.MethodsA total of 417 504 participants free of prior kidney diseases were included from UK Biobank. Handgrip strength was assessed by dynamometer. The walking pace was self-reported as slow, average, or brisk. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CKD.ResultsThe average age of the study population was 56.3 (SD, 8.1) years. 192 012 (46.0%) of the participants were male. The mean handgrip strength was 23.5 (SD, 6.2) and 40.0 (SD, 8.8) kg for females and males, respectively. Over a median follow-up duration of 12.1 years, 11 064 (2.7%) participants developed incident CKD. Handgrip strength was significantly inversely associated with the risk of incident CKD in both males and females (both P for trend <0.001). When handgrip strength was assessed as sex-specific quartiles, compared with those in the first quartile, the adjusted HRs (95% CI) of incident CKD in participants in the second, third and fourth quartiles were 0.84 (0.79, 0.89), 0.76 (0.71, 0.81) and 0.72 (0.67, 0.77), respectively. Compared with those with slow walking pace, participants with average (HR, 0.64; 95% CI: 0.60-0.68) or brisk (HR, 0.53; 95% CI: 0.49-0.57) walking pace had significantly lower risks of incident CKD. Compared with those with both lower handgrip strength (the first quartile) and slow walking pace, the lowest risk of incident CKD was observed in participants with both higher handgrip strength (the 2-4 quartiles) and average or brisk walking pace (HR, 0.51; 95% CI: 0.46-0.55).ConclusionsHandgrip strength and walking pace were significantly inversely associated with incident CKD in the general population.
| S-EPMC10067488 | biostudies-literature
Project description:AimsTo quantify the association of self-reported walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality.Methods and resultsA total of 230 670 women and 190 057 men free from prevalent cancer and cardiovascular disease were included from UK Biobank. Usual walking pace was self-defined as slow, steady/average or brisk. Handgrip strength was assessed by dynamometer. Cox-proportional hazard models were adjusted for social deprivation, ethnicity, employment, medications, alcohol use, diet, physical activity, and television viewing time. Interaction terms investigated whether age, body mass index (BMI), and smoking status modified associations. Over 6.3 years, there were 8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations of walking pace with mortality were modified by BMI. In women, the hazard ratio (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95% confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and 1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7 across all categories of BMI in men and women, with modest heterogeneity in men. Handgrip strength was associated with cardiovascular mortality in men only (HR tertile 1 vs. tertile 3 = 1.38; 1.18-1.62), without differences across BMI categories, while associations with all-cause mortality were only seen in men with low BMI. Associations for walking pace and handgrip strength with cancer mortality were less consistent.ConclusionA simple self-reported measure of slow walking pace could aid risk stratification for all-cause and cardiovascular mortality within the general population.
| S-EPMC5837337 | biostudies-literature
Project description:BackgroundTelomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences.MethodsIn this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL.Findings422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10-4) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL.InterpretationAlthough several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit.FundingUK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.
| S-EPMC9068584 | biostudies-literature