Telomere length and brain imaging phenotypes in UK Biobank

PLoS ONE, Год журнала: 2023, Номер 18(3), С. e0282363 - e0282363

Опубликована: Март 22, 2023

Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker biological aging. Short telomeres are associated with an increased risk neurological psychiatric disorders including dementia. The mechanism underlying this unclear, may involve brain structure function. However, relationship between telomere length neuroimaging markers poorly characterized. Here we show that leucocyte (LTL) multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL with: i) larger global subcortical grey matter volumes hippocampus, ii) lower T1-weighted grey-white tissue contrast sensory cortices, iii) white-matter microstructure measures corpus callosum association fibres, iv) volume white hyperintensities, v) basal ganglia iron. was against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91–0.96), but not stroke or Parkinson’s disease. multiple endophenotypes neurodegenerative disease, suggesting pathway by which longer confer

Язык: Английский

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Telomere Length and Symptoms of Attention Deficit and Hyperactivity Disorder in Children at 6–12 Years

Journal of Attention Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Objective: To explore the association between telomere length (TL) and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years. Method: Data from 1,759 belonging to HELIX project cohorts Asturias, Gipuzkoa Valencia of INMA were included. TL was determined by blood sample using a PCR protocol. ADHD described parents Conners’ Parent Rating Scale-Revised: Short Form. Multiple negative binomial regression models adjusted for potential confounders used estimate associations. Results: Overall estimates showed no associations symptoms. However, we observed that longer significantly associated with lower risk presenting (IRR = 0.93, 95% CI [0.87, 0.99]; p .022). Conclusion: While our study did not find consistent across all cohorts, significant found within cohort suggests may be linked Further research is needed this more detail.

Язык: Английский

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Mid‐life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants

Aging Cell, Год журнала: 2023, Номер 22(7)

Опубликована: Май 30, 2023

Abstract Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging‐related diseases, including Alzheimer's disease related dementias (AD/ADRD). The objective this study was assess associations leukocyte telomere length (TL) with AD/ADRD early markers AD/ADRD, cognitive performance brain magnetic resonance imaging (MRI) phenotypes. Data from European‐ancestry participants in the UK Biobank ( n = 435,046) were used evaluate whether mid‐life TL associated incident over a mean follow‐up 12.2 years. In subsample without data 43,390), we MRI phenotypes AD or vascular dementia pathology. Longer lower risk (adjusted Hazard Ratio [aHR] per SD 0.93, 95% CI 0.90–0.96, p 3.37 × 10 −7 ). also better specific domains, larger hippocampus volume, total volume white matter hyperintensities, higher fractional anisotropy diffusivity fornix. conclusion, longer inversely impairment, structural lesions toward development AD/ADRD. However, relationships between genetically determined outcomes above not statistically significant based on results Mendelian randomization analysis results. Our findings add literature prioritizing for causality needs ascertained mechanistic studies.

Язык: Английский

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Mendelian randomization and colocalization analyses reveal an association between short sleep duration or morning chronotype and altered leukocyte telomere length

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Окт. 6, 2023

Observational studies suggest certain sleep traits are associated with telomere length, but the causal nature of these associations is unclear. The study aimed to determine between 11 sleep-related and leukocyte length (LTL) through two-sample Mendelian randomization colocalization analyses using summary statistics from large-scale genome-wide association studies. Univariable indicates that genetically determined short decreased LTL, while morning chronotype increased LTL. Multivariable further supports findings analysis identifies shared common genetic variants for two associations. No evidence observed other Sensitivity MR methods, reverse re-running after removing potential pleiotropic enhance robustness results. These indicate prioritizing avoiding beneficial attenuating attrition. Consequently, addressing duration could serve as practical intervention strategies.

Язык: Английский

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Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation

Brain, Год журнала: 2024, Номер 147(10), С. 3395 - 3408

Опубликована: Март 8, 2024

Abstract Hearing difficulty (HD) is a major health burden in older adults. While ageing-related changes the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved HD predisposition. We analysed large-scale genome-wide association study (GWAS; ntotal = 501 825, 56% females) GWAS data related to 3935 imaging-derived phenotypes (IDPs) assessed up 33 224 individuals (52% using multiple MRI modalities. To investigate pleiotropy function, we conducted correlation, latent causal variable, Mendelian randomization multivariable generalized linear regression analyses. Additionally, performed local correlation multi-trait co-localization analyses identify genomic regions loci implicated pleiotropic mechanisms shared between IDPs. observed widespread of 120 IDPs females, 89 males 171 sex-combined analysis. The variable analysis showed that some these correlations due cause-effect relationships. For seven them, effects were confirmed by approach: vessel volume→HD analysis; hippocampus volume→HD, cerebellum grey matter primary visual cortex HD→fluctuation amplitudes node 46 resting-state functional dimensionality 100 females; global mean thickness→HD HD→mean orientation dispersion index superior corona radiata males. identified 13 signal for rs13026575 variant HD, volume SPTBN1 transcriptomic regulation females. Brain may have role sex differences predisposition via possible relationships regulatory mechanisms.

Язык: Английский

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Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июнь 20, 2024

Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice those pre-treated with antibiotics. Results: As a result, FMT specific modifications natural aging improved weight gain, extended telomere length, anti-oxidative stress tissue, regulated serum levels cytokine, balanced proportion Treg cells. Besides, increased abundance beneficial bacteria Lachnospiraceae , Dubosiella Bacteroides etc. decreased pathogenic Helicobacter Lachnoclostridium samples mice. This revealed remarkably reshaped microbiome. Additionally, FMT-treated showed metabolites Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic etc., which significantly positively correlated critical above. these identified mainly enriched pathways Amino acid metabolism, Lipid Nucleotide Furthermore, downregulated p53/p21/Rb signaling upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT following aging. Discussion: Overall, study demonstrates reprogramming by impedes process, possibly through regulation axis.

Язык: Английский

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Understanding the health effects of caregiving stress: New directions in molecular aging

Ageing Research Reviews, Год журнала: 2023, Номер 92, С. 102096 - 102096

Опубликована: Окт. 28, 2023

Язык: Английский

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Reverse causal relationship between periodontitis and shortened telomere length: Bidirectional two-sample Mendelian random analysis

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 19, 2022

Observational studies have demonstrated a link between shortened telomere lengths(TL) and chronic periodontitis. However, whether the TL is cause or result of periodontitis unknown.Therefore, our objective was to investigate bidirectional causal relationship using two-sample Mendel randomized (MR) study.A MR analysis publicly available genome-wide association study (GWAS) data used. As primary analysis, inverse variance weighting (IVW) employed. To identify pleiotropy, we used leave-one-out MR-Egger, Weighted median, Simple mode, pleiotropy residual sum outlier (MR-PRESSO).In reverse results, genetic prediction short causally associated with higher risk (IVW: odds ratio [OR]: 1.0601, 95% confidence interval [CI]: 1.0213 1.1002; P =0.0021) other complementary methods. In forward shown no significant effect on p = 0.7242), consistent results for remaining MR. No detected in sensitivity (all P>0.05).Our showed relationship, shorten being linked periodontitis, rather than that TL. Future research needed cell senescence disease.

Язык: Английский

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Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Journal of Integrative Neuroscience, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 23, 2025

Background: Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and indicators are significantly changed ASD patients compared with controls remains controversial. The aim this study was determine the associations TL performing meta-analysis all published evidence. Methods: PubMed Embase databases were searched for articles up April, 2024. effect size expressed as standardized mean difference (SMD) 95% confidence interval (CI) via Stata 15.0 software. Results: Thirty-nine studies included. Pooled results showed that controls, children adolescents associated shorter (SMD = –0.48; CI –0.66– –0.29; p < 0.001; particularly males), lower total antioxidant capacity (TAC: SMD –1.15; –2.01– –0.30; 0.008), higher DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG: 0.63; 0.03–1.23; 0.039), lipid (hexanolyl-lysine, HEL: 0.37; 0.13–0.62; 0.003), protein (3-nitrotyrosine, 3-NT: 0.86; 0.21–1.51; 0.01; dityrosine, DT: 0.66; 0.521–0.80; 0.01) damage. There no significant differences between 8-isoprostane index after publication bias correction, N-formylkynurenine during overall meta-analysis. Conclusions: TL, 8-OHdG, TAC, HEL, 3-NT, DT represent potential biomarkers prediction adolescents.

Язык: Английский

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The Executive Functioning of the Chief Executive

Опубликована: Янв. 1, 2025

Язык: Английский

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