Epigenetic Association Analyses and Risk Prediction of RLS DOI Creative Commons

Philip Harrer,

Nazanin Mirza‐Schreiber, Vanessa Mandel

et al.

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(8), P. 1410 - 1418

Published: May 22, 2023

ABSTRACT Background As opposed to other neurobehavioral disorders, epigenetic analyses and biomarkers are largely missing in the case of idiopathic restless legs syndrome (RLS). Objectives Our aims were develop a biomarker for RLS based on DNA methylation blood examine brain tissues dissecting pathophysiology. Methods Methylation from three independent cohorts (n = 2283) post‐mortem two 61) was assessed by Infinium EPIC 850 K BeadChip. Epigenome‐wide association study (EWAS) results individual combined random‐effect meta‐analysis. A three‐stage selection procedure (discovery, n 884; testing, 520; validation, 879) established an risk score including 30 CpG sites. Epigenetic age Horvath's multi‐tissue clock Shireby's cortical clock. Results EWAS meta‐analysis revealed 149 sites linked 136 genes ( P < 0.05 after Bonferroni correction) 23 18 (false discovery rate [FDR] 5%). Gene‐set suggested enrichments tissue types subunits kainate‐selective glutamate receptor complex. Individual candidate could be assigned neurodevelopmental or metabolic traits. The achieved area under curve (AUC) 0.70 (0.67–0.73) validation set, comparable analogous scores disorders. significant difference biological patients not detectable. Conclusions supports notion altered neurodevelopment RLS. reliably associated with but require even higher accuracy useful as biomarkers. © 2023 Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Geroscience-Centric Perspective for Geriatric Psychiatry: Integrating Aging Biology With Geriatric Mental Health Research DOI Open Access
Breno S. Diniz, Johanna Seitz‐Holland, Raghav Sehgal

et al.

American Journal of Geriatric Psychiatry, Journal Year: 2023, Volume and Issue: 32(1), P. 1 - 16

Published: Sept. 23, 2023

Language: Английский

Citations

9
Accelerated epigenetic age is associated with whole-brain functional connectivity and impaired cognitive performance in older adults DOI Creative Commons
Andrew J. Graves, Joshua S. Danoff, Minah Kim

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 26, 2024

Abstract While chronological age is a strong predictor for health-related risk factors, it an incomplete metric that fails to fully characterize the unique aging process of individuals with different genetic makeup, neurodevelopment, and environmental experiences. Recent advances in epigenomic array technologies have made possible generate DNA methylation-based biomarkers biological aging, which may be useful predicting myriad cognitive abilities functional brain network organization across older individuals. It currently unclear domains are negatively correlated epigenetic above beyond age, unknown if important mechanism explaining these associations. In this study, accelerated (i.e. AgeAccelGrim) performed worse on tasks spanned wide variety faculties including both fluid crystallized intelligence ( N = 103, average 68.98 years, 73 females, 30 males). Additionally, fMRI connectome-based predictive models suggested mediating connectivity acceleration-cognition associations primarily medial temporal lobe limbic structures. This research highlights role processes development maintenance healthy capacities function brain.

Language: Английский

Citations

3
Can accelerated ageing models inform us on age‐related tauopathies? DOI Creative Commons
Zhuang Zhuang Han, Alex Fleet, Delphine Larrieu

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(5)

Published: April 3, 2023

Ageing is the greatest risk factor of late-onset neurodegenerative diseases. In realm sporadic tauopathies, modelling process biological ageing in experimental animals forms foundation searching for molecular origin pathogenic tau and developing potential therapeutic interventions. Although prior research into transgenic models offers valuable lessons studying how mutations overexpression can drive pathologies, underlying mechanisms by which leads to abnormal accumulation remains poorly understood. Mutations associated with human progeroid syndromes have been proposed be able mimic an aged environment animal models. Here, we summarise recent attempts relation tauopathies using that carry syndromes, or genetic elements unrelated exceptional natural lifespans, a remarkable resistance ageing-related disorders.

Language: Английский

Citations

8
Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood DOI Creative Commons
Klára Marečková, Anna Pačínková, Radek Mareček

et al.

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Aug. 1, 2023

The proportion of older adults within society is sharply increasing and a better understanding how we age starts to be critical. However, given the paucity longitudinal studies with both neuroimaging epigenetic data, it remains largely unknown whether speed clock changes over life course any such are proportional in brain aging cognitive skills. To fill these knowledge gaps, conducted study prenatal birth cohort, studied across adolescence young adulthood, evaluated its relationship outcomes.DNA methylation was assessed using Illumina EPIC Platform adolescence, early late 20 s, DNA estimated Horvath's clock, gap (EpiAGE) calculated as residualized for batch, chronological epithelial cells. Structural magnetic resonance imaging (MRI) acquired s same 3T Prisma MRI scanner Neuroanatomical Age Prediction R (NAPR) platform. Cognitive skills were Wechsler Adult Intelligence Scale (WAIS) s.The EpiAGE positively correlated (r = 0.34-0.47), suggesting that relatively stable characteristic an individual. Further, faster pace between measurements at end period 0.48-0.77) but negatively earlier time point -0.42 -0.55), compensatory mechanism where matures might catching up matures. Finally, higher positive showed small (Adj R2 0.03) significant relationships all participants lower full-scale IQ adult women s.We conclude individual shows only accelerated women-specific worse performance IQ.

Language: Английский

Citations

8
Mitigating cellular aging and enhancing cognitive functionality: visual arts-mediated Cognitive Activation Therapy in neurocognitive disorders DOI Creative Commons
Manuela Campisi, Luana Cannella, Dilek Celik

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: March 8, 2024

The growing phenomenon of population aging is redefining demographic dynamics, intensifying age-related conditions, especially dementia, projected to triple by 2050 with an enormous global economic burden. This study investigates visual arts-mediated Cognitive Activation Therapy (CAT) as a non-pharmacological CAT intervention targets both biological [leukocyte telomere length (LTL), DNA methylation age (DNAmAge)] and cognitive functionality. Aligning broader trend integrating approaches into dementia care. longitudinal involved 20 patients mild moderate neurocognitive disorders. functional assessments, markers -i.e., LTL DNAmAge- were analyzed before after intervention. Change in was positively correlated days treatment ( p =0.0518). significantly elongated =0.0269), men =0.0142), correlating younger =0.0357), higher education =0.0008). DNAmAge remained instead stable post-treatment. improvements observed for Copy complex geometric figure, Progressive Silhouettes, Position Discrimination, Communication Activities Daily Living—Second edition, Direct Functional Status &lt; 0.0001) Object decision =0.0594), but no correlations found between gains. Visual effectively mitigates cellular aging, men, elongating LTL. These findings underscore the potential interventions enhancing status general well-being Further research larger longer-term studies essential validation.

Language: Английский

Citations

2
The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study DOI Creative Commons

Jingqi Fan,

Qing Liu, Xin Liu

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging diseases. Our study employed bidirectional two-sample Mendelian randomization (MR) design to assess potential causal association epigenetic We utilized publicly available summary datasets from several genome-wide studies (GWAS). investigation focused on multiple measures of age exposures outcomes, while occurrence diseases served outcomes. Sensitivity analyses confirmed accuracy results. The results show significant decrease in Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, p 0.03638). Additionally, we identified that HannumAge was linked an increased Multiple Sclerosis 1.0707, 1.0056-1.1401, 0.03295). Furthermore, also found estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated Alzheimer's 1.0001, 1.0000-1.0002, 0.04425). Beyond that, did observe any associations risk. findings firstly provide evidence Exploring perspective contribute diagnosis, prognosis, treatment

Language: Английский

Citations

2
The mechanisms, hallmarks, and therapies for brain aging and age-related dementia DOI Creative Commons
Shiyun Jin, Wenping Lü,

Juan Zhang

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

2
Comprehensive analysis of molecular, physiological, and functional biomarkers of aging with neurological diseases using Mendelian randomization DOI Creative Commons

Y Imahori,

Chenxi Qin,

Bowen Tang

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

Citations

2
Associations of combined accelerated biological aging and genetic susceptibility with incident dementia: a prospective study in the UK Biobank DOI Creative Commons
Zirong Ye, Haoxiang Lang,

Zishan Xie

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 30, 2024

Language: Английский

Citations

2
DNA Methylation and Telomeres—Their Impact on the Occurrence of Atrial Fibrillation during Cardiac Aging DOI Open Access
Arkadiusz Grzeczka, Szymon Graczyk, Paweł Kordowitzki

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15699 - 15699

Published: Oct. 28, 2023

Atrial fibrillation (AF) is the most common arrhythmia in humans. AF characterized by irregular and increased atrial muscle activation. This high-frequency activation obliterates synchronous work of atria ventricles, reducing myocardial performance, which can lead to severe heart failure or stroke. The risk developing depends largely on patient's history. Cardiovascular diseases are considered aging-related pathologies; therefore, deciphering role telomeres DNA methylation (mDNA), two hallmarks aging, likely contribute a better understanding prophylaxis AF. In honor Prof. Elizabeth Blackburn's 75th birthday, we dedicate this review discovery her contribution research aging.

Language: Английский

Citations

6