Is telomere length a biomarker for aging: cross-sectional evidence from the west of Scotland?

Background <p> The search for biomarkers of aging (BoAs) has been largely unsuccessful to-date and there is widespread skepticism about the prospects of finding any that satisfy the criteria developed by the American Federation of Aging Research. This may be because the criteria are too strict or because a composite measure might be more appropriate. Telomere length has attracted a great deal of attention as a candidate BoA. We investigate whether it meets the criteria to be considered as a single biomarker of aging, and whether it makes a useful contribution to a composite measure. </p> Methodology/Principal Findings <p> Using data from a large population based study, we show that telomere length is associated with age, with several measures of physical and cognitive functioning that are related to normal aging, and with three measures of overall health. In the majority of cases, telomere length adds predictive power to that of age, although it was not nearly as good a predictor overall. We used principal components analysis to form two composites from the measures of functioning, one including telomere length and the other not including it. These composite BoAs were better predictors of the health outcomes than chronological age. There was little difference between the two composites. </p> Conclusions <p> Telomere length does not satisfy the strict criteria for a BoA, but does add predictive power to that of chronological age. Equivocal results from previous studies might be due to lack of power or the choice of measures examined together with a focus on single biomarkers. Composite biomarkers of aging have the potential to outperform age and should be considered for future research in this area.</p&gt

Insomnia symptoms as a cause of type 2 diabetes Incidence: a 20 year cohort study

Background Insomnia symptoms are associated with type 2 diabetes incidence but are also associated with a range of potential time-varying covariates which may confound and/or mediate associations. We aimed to assess whether cumulative exposure to insomnia symptoms has a causal effect on type 2 diabetes incidence. Methods A prospective cohort study in the West of Scotland, following respondents for 20 years from age 36. 996 respondents were free of diabetes at baseline and had valid data from up to four follow-up visits. Type 2 diabetes was assessed at the final visit by self-report, taking diabetic medication, or blood-test (HbA1c ≥ 6.5% or 48 mmol/mol). Effects of cumulative insomnia exposure on type 2 diabetes incidence were estimated with traditional regression and marginal structural models, adjusting for time-dependent confounding (smoking, diet, physical inactivity, obesity, heavy drinking, psychiatric distress) as well as for gender and baseline occupational class. Results Traditional regression yielded an odds ratio (OR) of 1.34 (95% CI: 1.06-1.70) for type 2 diabetes incidence for each additional survey wave in which insomnia was reported. Marginal structural models adjusted for prior covariates (assuming concurrently measured covariates were potential mediators), reduced this OR to 1.20 (95% CI: 0.98-1.46), and when concurrent covariates were also included (viewing them as potential confounders) this dropped further to 1.08 (95% CI: 0.85-1.37). Conclusions The association between cumulative experience of insomnia and type 2 diabetes incidence appeared confounded. Evidence for a residual causal effect depended on assumptions as to whether concurrently measured covariates were confounders or mediator

On the evolution of the intrinsic scatter in black hole versus galaxy mass relations

We present results on the evolution of the intrinsic scatter of black hole masses considering different implementations of a model in which black holes only grow via mergers. We demonstrate how merger driven growth affects the correlations between black hole mass and host bulge mass. The simple case of an initially log-normal distributed scatter in black hole and bulge masses combined with random merging within the galaxy population results in a decreasing scatter with merging generation/number as predicted by the Central-limit theorem. In general we find that the decrease in scatter {\sigma} is well approximated by {\sigma}merg(m) = {\sigma}ini \times (m + 1)^(-a/2) with a = 0.42 for a range of mean number of mergers m < 50. For a large mean number of mergers (m > 100) we find a convergence to a = 0.61. This is valid for a wide range of different initial distributions, refill-scenarios or merger mass-ratios. Growth scenarios based on halo merger trees of a (100 Mpc)^3 dark matter LambdaCDM-simulation show a similar behaviour with a scatter decrease of a = 0.30 with typical number of mergers m < 50 consistent with random merging (best matching model: a = 0.34). Assuming a present day scatter of 0.3 dex in black hole mass and a mean number of mergers not exceeding m = 50 our results imply a scatter of 0.6 dex at z = 3 and thus a possible scenario in which overmassive (and undermassive) black holes at high redshift are a consequence of a larger intrinsic scatter in black hole mass. A simple toy model connecting the growth of black holes to the growth of LambdaCDM dark matter halos via mergers, neglecting any contribution from accretion, yields a consistent M\cdot -MBulge relation at z = 0 - if we assume the correct initial relation.Comment: 19 pages, 21 figures, accepted for publication in MNRA

The role of material, psychosocial and behavioral factors in mediating the association between socioeconomic position and allostatic load (measured by cardiovascular, metabolic and inflammatory markers)

Lower socioeconomic position (SEP), both accumulated across the life course and at different life-stages, has been found to be associated with higher cumulative physiological burden, as measured by allostatic load. This study aimed to identify what factors mediate the association between SEP and allostatic load, as measured through combining cardiovascular, metabolic and inflammatory markers. We explored the role of material, psychological and behavioral factors, accumulated across two periods in time, in mediating the association between SEP and allostatic load. Data are from the West of Scotland Twenty-07 Study, with respondents followed over five waves of data collection from ages 35 to 55 (n=999). Allostatic load was measured by summing nine binary biomarker scores ('1'= in the highest-risk quartile) measured when respondents were 55. years old (wave 5). SEP was measured by a person's accumulated social class over two periods All mediators and SEP were measured at baseline in 1987 and 20. years later and combined to form accumulated measures of risk. Material mediators included car and home ownership, and having low income. The General Health Questionnaire (GHQ-12) was used as the psychosocial mediator. Behavioral mediators included smoking, alcohol consumption, physical activity and diet. Path analysis using linear regressions adjusting for sex were performed for each of the potential mediators to assess evidence of attenuation in the association between lower SEP and higher allostatic load. Analyses by mediator type revealed that renting one's home (approximately 78% attenuation) and having low income (approx. 62% attenuation) largely attenuated the SEP-allostatic load association. GHQ did not attenuate the association. Smoking had the strongest attenuating effect of all health behaviors (by 33%) with no other health behaviors attenuating the association substantially. Material factors, namely home tenure and income status, and smoking have important roles in explaining socioeconomic disparities in allostatic load, particularly when accumulated over time

Case report: Adult-onset limb girdle muscular dystrophy in sibling pair due to novel homozygous LAMA2 missense variant

Recessive pathogenic variants in the laminin subunit alpha 2 (LAMA2) gene cause a spectrum of disease ranging from severe congenital muscular dystrophy to later-onset limb girdle muscular dystrophy (LGMDR23). The phenotype of LGMDR23 is characterized by slowly progressive proximal limb weakness, contractures, raised creatine kinase, and sometimes distinctive cerebral white matter changes and/or epilepsy. We present two siblings, born to consanguineous parents, who developed adult-onset LGMDR23 associated with typical cerebral white matter changes and who both later developed dementia. The male proband also had epilepsy and upper motor neuron signs when he presented at age 72. Merosin immunohistochemistry and Western blot on muscle biopsies taken from both subjects was normal. Whole exome sequencing revealed a previously unreported homozygous missense variant in LAMA2 [Chr6(GRCh38):g.129297734G&gt;A; NM_000426.3:c.2906G&gt;A; p.(Cys969Tyr)] in the proband. The same homozygous LAMA2 variant was confirmed by Sanger sequencing in the proband's affected sister. These findings expand the genotypic and phenotypic spectrum of LGMDR23

Predictors of COVID-19 vaccine hesitancy in the UK household longitudinal study

Vaccine hesitancy could undermine efforts to control COVID-19. We investigated the prevalence of COVID-19 vaccine hesitancy in the UK and identified vaccine hesitant subgroups. The ‘Understanding Society’ COVID-19 survey asked participants (n = 12,035) their likelihood of vaccine uptake and reason for hesitancy. Cross-sectional analysis assessed vaccine hesitancy prevalence and logistic regression calculated odds ratios. Overall vaccine hesitancy was low (18% unlikely/very unlikely). Vaccine hesitancy was higher in women (21.0% vs 14.7%), younger age groups (26.5% in 16–24 year olds vs 4.5% in 75 + ) and those with lower education levels (18.6% no qualifications vs 13.2% degree qualified). Vaccine hesitancy was high in Black (71.8%) and Pakistani/Bangladeshi (42.3%) ethnic groups. Odds ratios for vaccine hesitancy were 13.42 (95% CI:6.86, 26.24) in Black and 2.54 (95% CI:1.19, 5.44) in Pakistani/Bangladeshi groups (compared to White British/Irish) and 3.54 (95% CI:2.06, 6.09) for people with no qualifications versus degree. Urgent action to address hesitancy is needed for some but not all ethnic minority groups

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: Methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD)

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria > 30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated GFR (eGFR). RESULTS: 2996 participants were enrolled. Median (interquartile range) age was 66 (54 to 74) years, 58.5% were male, eGFR 33.8 (24.0 to 46.6) ml/min/1.73m2 and UACR 209 (33 to 926) mg/g. 1883 participants (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and investigate underlying mechanisms to inform new treatment development

Socioeconomic position across the lifecourse & allostatic load: data from the West of Scotland Twenty-07 cohort study

Background: We examined how socioeconomic position (SEP) across the lifecourse (three critical periods, social mobility and accumulated over time) is associated with allostatic load (a measure of cumulative physiological burden). Methods. Data are from the West of Scotland Twenty-07 Study, with respondents aged 35 (n = 740), 55 (n = 817) and 75 (n = 483). SEP measures representing childhood, the transition to adulthood and adulthood SEP were used. Allostatic load was produced by summing nine binary biomarker scores (1 = in the highest-risk quartile). Linear regressions were used for each of the lifecourse models; with model fits compared using partial F-tests. Results: For those aged 35 and 55, higher SEP was associated with lower allostatic load (no association in the 75-year-olds). The accumulation model (more time spent with higher SEP) had the best model fit in those aged 35 (b = -0.50, 95%CI = -0.68, -0.32, P = 0.002) and 55 (b = -0.31, 95%CI = -0.49, -0.12, P < 0.001). However, the relative contributions of each life-stage differed, with adulthood SEP less strongly associated with allostatic load. Conclusions: Long-term, accumulated higher SEP has been shown to be associated with lower allostatic load (less physiological burden). However, the transition to adulthood may represent a particularly sensitive period for SEP to impact on allostatic load. © 2014 Robertson et al.; licensee BioMed Central Ltd