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

Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective DOI Creative Commons
Stefano Salvioli, Maria Sofia Basile, Leonardo Bencivenga

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102044 - 102044

Published: Aug. 28, 2023

According to the Geroscience concept that organismal aging and age-associated diseases share same basic molecular mechanisms, identification of biomarkers age can efficiently classify people as biologically older (or younger) than their chronological (i.e. calendar) is becoming paramount importance. These will be in fact at higher lower) risk for many different diseases, including cardiovascular neurodegeneration, cancer, etc. In turn, patients suffering from these are healthy age-matched individuals. Many correlate with have been described so far. The aim present review discuss usefulness some (especially soluble, circulating ones) order identify frail patients, possibly before appearance clinical symptoms, well diseases. An overview selected discussed this regard, particular we focus on related metabolic stress response, inflammation, cell death (in neurodegeneration), all phenomena connected inflammaging (chronic, low-grade, inflammation). second part review, next-generation markers such extracellular vesicles cargos, epigenetic gut microbiota composition, discussed. Since recent progresses omics techniques allowed an exponential increase production laboratory data also field age, making it difficult extract biological meaning huge mass available data, Artificial Intelligence (AI) approaches increasingly important strategy extracting knowledge raw providing practitioners actionable information treat patients.

Language: Английский

Citations

28
Epigenetic clocks in neurodegenerative diseases: a systematic review DOI

Tianmi Yang,

Yi Xiao, Yangfan Cheng

et al.

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2023, Volume and Issue: 94(12), P. 1064 - 1070

Published: March 24, 2023

Background Biological ageing is one of the principal risk factors for neurodegenerative diseases. It becoming increasingly clear that acceleration DNA methylation age, as measured by epigenetic clock, closely associated with many age-related Methods We searched PubMed and Web Science databases to identify eligible studies reporting clocks in several diseases, including Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) Huntington’s (HD). Results Twenty-three (12 AD, 4 PD, 5 ALS, 2 HD) were included. systematically summarised clinical utility 11 (based on blood brain tissues) assessing factors, age onset, diagnosis, progression, prognosis pathology ALS HD. also critically described our current understandings these evidences, further discussed key challenges, potential mechanisms future perspectives Conclusions Epigenetic hold great Further research encouraged evaluate promote application. PROSPERO registration number CRD42022365233.

Language: Английский

Citations

22
Diet, Pace of Biological Aging, and Risk of Dementia in the Framingham Heart Study DOI
Aline Thomas, Calen P. Ryan, Avshalom Caspi

et al.

Annals of Neurology, Journal Year: 2024, Volume and Issue: 95(6), P. 1069 - 1079

Published: Feb. 26, 2024

People who eat healthier diets are less likely to develop dementia, but the biological mechanism of this protection is not well understood. We tested hypothesis that healthy diet protects against dementia because it slows pace aging.

Language: Английский

Citations

6
CpGPT: a Foundation Model for DNA Methylation DOI Creative Commons
Lucas Paulo de Lima Camillo, Raghav Sehgal, Judith Armstrong

et al.

Published: Oct. 29, 2024

Abstract DNA methylation is a critical epigenetic modification that regulates gene expression and plays significant role in development disease processes. Here, we present the Cytosine-phosphate-Guanine Pretrained Transformer (CpGPT), novel foundation model pretrained on over 1,500 datasets encompassing 100,000 samples from diverse tissues conditions. CpGPT leverages an improved transformer architecture to learn comprehensive representations of patterns, allowing it impute reconstruct genome-wide profiles limited input data. By capturing sequence, positional, contexts, outperforms specialized models when finetuned for aging-related tasks, including chronological age prediction, mortality risk, morbidity assessments. The highly adaptable across different platforms tissue types. Furthermore, analysis sample-specific attention weights enables identification most influential CpG sites individual predictions. As model, sets new benchmark analysis, achieving strong performance Biomarkers Aging Challenge, where placed second overall estimation first public leaderboard methylation-based prediction. Highlights 100,000+ samples. demonstrates zero-shot tasks imputation, array conversion, reference mapping. achieves state-of-the-art results prediction estimation. Sample-specific interpretability enabled through weights.

Language: Английский

Citations

5
DNA methylation-based measures of biological aging and cognitive decline over 16-years: preliminary longitudinal findings in midlife DOI Creative Commons
Rebecca G. Reed, Judith Carroll, Anna L. Marsland

et al.

Aging, Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 11, 2022

DNA methylation-based (DNAm) measures of biological aging associate with increased risk morbidity and mortality, but their links cognitive decline are less established. This study examined changes over a 16-year interval in epigenetic clocks (the traditional principal components [PC]-based Horvath, Hannum, PhenoAge, GrimAge) pace (Dunedin PoAm, Dunedin PACE) 48 midlife adults enrolled the longitudinal arm Adult Health Behavior project (56% Female, baseline AgeM = 44.7 years), selected for discrepant trajectories. Cognitive Decliners (N 24) were based on declines composite score derived from neuropsychological tests matched participants who did not show any decline, Maintainers 24). Multilevel models repeated DNAm within person tested main effects time, group, group by time interactions. significantly generally consistent elapsed between visits. There also differences: overall, had an older PC-GrimAge faster than Maintainers. no significant interactions, suggesting accelerated remained constant time. Older may be particularly sensitive to midlife.

Language: Английский

Citations

20
Exploring the epigenome to identify biological links between the urban environment and neurodegenerative disease: an evidence review DOI Creative Commons
S. W. Glover, Claire Hill, Bernadette McGuinness

et al.

Cities & Health, Journal Year: 2024, Volume and Issue: 8(6), P. 1153 - 1175

Published: April 15, 2024

Global urbanisation has occurred in tandem with population ageing, having implications on human cognitive health. Urban environmental factors such as air pollution are known risk of impairment and neurodegenerative disease. However, due to the sparse evidence base, biological pathways by which urban operate not well understood. The aim this review is explain how exploring epigenome (i.e. chemical modifications genome do change underlying gene sequence) can further our understanding these pathways. influenced for Utilising complex epigenetic analytical techniques including clocks, Mendelian randomization multi-omic approaches, it possible identify consequences biology. Through better modifications, be inherited or dynamically response exposures, impact outcomes, we work encourage development public health policies, planning design policies reduce burden disease healthier ageing older adult population.

Language: Английский

Citations

4
Proteomics-based aging clocks in midlife and late-life and risk of dementia DOI Creative Commons
Sanaz Sedaghat, Saeun Park, Rob F. Walker

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Background: Biological age can be quantified by composite proteomic scores, called aging clocks. We investigated whether biological acceleration (a discrepancy between chronological and age) in midlife late-life is associated with cognitive function risk of dementia. Methods: used two population-based cohort studies: Atherosclerosis Risk Communities (ARIC) Study Multi-Ethnic (MESA). Proteomics-based clocks (PACs) were created ARIC at (mean age: 58 years, n=11,758) 77 n=4,934) using elastic net regression models two-thirds dementia-free participants validated the remaining one-third participants. Age (AA) was calculated as residuals after regressing PACs on age. PAC MESA 62 n=5,829). multivariable linear Cox proportional hazards to assess association AA dementia incidence, respectively. Results: In ARIC, every five years lower global function: difference: -0.11, 95% confidence interval (CI): -0.16, -0.06) -0.17, CI: -0.23, -0.12 AA. Consistently, higher (hazard ratio [HR]: 1.20 [CI: 1.04, 1.36]) more prominently when (HR: 2.14 [CI:1.67, 2.73]). Similar findings observed study: (difference: -0.08 -0.14, -0.03]) (HR:1.23 1.46]). Conclusion: Accelerated – defined plasma proteome predicts a late-life.

Language: Английский

Citations

0
Epigenetic age acceleration is related to cognitive decline in the elderly: Results of the Austrian Stroke Prevention Study DOI Creative Commons
Piyush Gampawar, Sai Pavan Kumar Veeranki,

Katja-Elisabeth Petrovic

et al.

Psychiatry and Clinical Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Epigenetic clocks, quantifying biological age through DNA methylation (DNAmAge), have emerged as potential indicators of brain aging. As the variety DNAmAge algorithms grows, consensus on their efficacy in predicting age-related changes is lacking. This study aimed to explore intricate relationship between diverse and structural cognitive markers Within a cohort 796 elderly patients (mean age, 65.8 ± 7.9 years), we scrutinized 11 algorithms, including Horvath, Hannum, Zhang's PhenoAge, GrimAge, DunedinPACE, principal component (PC)-based PCHorvath, PCHannum, PCPhenoAge, PCGrimAge. We evaluated association with baseline cognition decline, assessed follow-up evaluations at three (T1) six (T2) years postbaseline. Additionally, examined magnetic resonance imaging aging, white matter. clock was best predictor decline memory (β = -0.04) global -0.03), whereas PCGrimAge speed -0.17). The were second-best predictors explaining variability after education (R2 partial 1.66% 2.82%) for 2.13%). PC-trained outperformed respective original version. are strong independent normal population explain additional beyond that accounted by conventional risk factors.

Language: Английский

Citations

0
Longitudinal associations of epigenetic aging with cognitive aging in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos DOI
Myriam Fornage, Wassim Tarraf, Rui Xia

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Due to the paucity of longitudinal DNA methylation data (DNAm), especially among Hispanic/Latino adults, association between changes in epigenetic clocks over time and cognitive aging phenotypes has not been investigated. This study included 2671 adults (57 years; 66% women) with blood DNAm neurocognitive function assessed at two visits approximately 7 years apart. We evaluated associations 5 their between-visit change multiple measures that a global score each visit, score, MCI diagnosis, presence significant decline visit 2 (V2). There were greater acceleration for all lower visit. The strongest observed GrimAge DunedinPACE. Similar results domain-specific diagnosis V2. was increase age PhenoAge GrimAge. Between-visit these also associated risk Epigenetic is function, decline, adults. Longitudinal assessment second-generation clocks, may provide additional value predicting beyond single point assessment.

Language: Английский

Citations

0
Epigenetic Age Acceleration in Frontotemporal Lobar Degeneration: A Comprehensive Analysis in the Blood and Brain DOI Creative Commons
Megha Murthy, Patrizia Rizzu, Peter Heutink

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(14), P. 1922 - 1922

Published: July 24, 2023

Frontotemporal lobar degeneration (FTLD) includes a heterogeneous group of disorders pathologically characterized by the frontal and temporal lobes. In addition to major genetic contributors FTLD such as mutations in MAPT, GRN, C9orf72, recent work has identified several epigenetic modifications including significant differential DNA methylation DLX1, OTUD4 loci. As aging remains one risk factors for FTLD, we investigated presence accelerated compared controls. We calculated age both peripheral blood brain tissues multiple subtypes using clocks, i.e., DNAmClockMulti, DNAmClockHannum, DNAmClockCortical, GrimAge, PhenoAge, determined acceleration its association with different cellular proportions clinical traits. Significant was observed frontotemporal dementia (FTD) progressive supranuclear palsy (PSP) patients controls even after accounting confounding factors. A similar trend DNAmClockMulti DNAmClockCortical post-mortem cortex tissue PSP cases harboring GRN mutations. Our findings support that increased could be an indicator smaller extent, FTD.

Language: Английский

Citations

10