A comprehensive map of the aging blood methylome in humans DOI Creative Commons
Kirsten Seale, Andrew E. Teschendorff,

Alexander P. Reiner

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Sept. 6, 2024

Language: Английский

Challenges and perspectives in computational deconvolution of genomics data DOI

Lana X. Garmire,

Yijun Li, Qianhui Huang

et al.

Nature Methods, Journal Year: 2024, Volume and Issue: 21(3), P. 391 - 400

Published: Feb. 19, 2024

Language: Английский

Citations

20

Cigarette Smoking and E-cigarette Use Induce Shared DNA Methylation Changes Linked to Carcinogenesis DOI Creative Commons
Chiara Herzog, Allison Jones, Iona Evans

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(11), P. 1898 - 1914

Published: March 19, 2024

Abstract Tobacco use is a major modifiable risk factor for adverse health outcomes, including cancer, and elicits profound epigenetic changes thought to be associated with long-term cancer risk. While electronic cigarettes (e-cigarettes) have been advocated as harm reduction alternatives tobacco products, recent studies revealed potential detrimental effects, highlighting the urgent need further research into molecular impacts of e-cigarettes. Here, we applied computational deconvolution methods dissect cell- tissue-specific effects or e-cigarette on DNA methylation (DNAme) in over 3,500 buccal/saliva, cervical, blood samples, spanning epithelial immune cells at directly indirectly exposed sites. The 535 identified smoking-related DNAme loci [cytosine-phosphate-guanine sites (CpG)] clustered four functional groups, detoxification growth signaling, based cell type anatomic site. Loci hypermethylated buccal smokers NOTCH1/RUNX3/growth receptor signaling also exhibited elevated tissue progressing lung carcinoma situ lesions, hypermethylation these predicted development samples collected from up 22 years prior diagnosis, suggesting role driving carcinogenesis. Alarmingly, CpGs were users limited smoking history. This study sheds light type–specific landscape induced by products. Significance: both e-cigarettes exposure-specific that are predictive carcinogenesis, caution when broadly recommending aids cessation.

Language: Английский

Citations

19

Epigenetic ageing clocks: statistical methods and emerging computational challenges DOI
Andrew E. Teschendorff, Steve Horvath

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

Citations

6

Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways DOI Creative Commons

Taekyung Ryu,

Kyungdo Kim, Nicholas Asiimwe

et al.

PROTEOMICS, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

ABSTRACT Alzheimer's disease (AD) is a leading cause of dementia, but the pathogenesis mechanism still elusive. Advances in proteomics have uncovered key molecular mechanisms underlying AD, revealing complex network dysregulated pathways, including amyloid metabolism, tau pathology, apolipoprotein E (APOE), protein degradation, neuroinflammation, RNA splicing, metabolic dysregulation, and cognitive resilience. This review examines recent proteomic findings from AD brain tissues biological fluids, highlighting potential biomarkers therapeutic targets. By examining landscape them, we aim to deepen our understanding support developing precision medicine strategies for more effective interventions.

Language: Английский

Citations

1

Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review DOI Creative Commons
Amery Treble‐Barna, Lacey W. Heinsberg,

Zachary Stec

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 147, P. 105078 - 105078

Published: Feb. 9, 2023

Language: Английский

Citations

20

Quantifying the proportion of different cell types in the human cortex using DNA methylation profiles DOI Creative Commons
Eilís Hannon, Emma Dempster, Jonathan Davies

et al.

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

Published: Jan. 25, 2024

Due to interindividual variation in the cellular composition of human cortex, it is essential that covariates capture these differences are included epigenome-wide association studies using bulk tissue. As experimentally derived cell counts often unavailable, computational solutions have been adopted estimate proportion different types DNA methylation data. Here, we validate and profile use an expanded reference dataset incorporating two neuronal three glial subtypes for quantifying cortex.

Language: Английский

Citations

6

Cumulative stress across the lifecourse and biological aging in adulthood DOI
Shakira F. Suglia, Elizabeth S. Clausing, Rachel C. Shelton

et al.

Psychosomatic Medicine, Journal Year: 2024, Volume and Issue: 86(3), P. 137 - 145

Published: Jan. 10, 2024

ABSTRACT Objective Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies examined across the life course relation to aging. Methods In 359 individuals (57% White, 34% Black) from Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) traumatic (death of a sibling or child, violence exposure) were assessed at multiple time points (birth ages 9, 15, 50 years). Experiences major discrimination age 50. Life period stress scores then as childhood (birth–age 15 years) adulthood (age At years, participants provided blood samples, DNA methylation was EPIC BeadChip. Epigenetic estimated using six epigenetic clocks (Horvath, Hannum, Skin Blood age, PhenoAge, GrimAge, Dunedin Pace Aging). Age acceleration determined residuals regressing chronologic on each metrics. Telomere length quantitative polymerase chain reaction–based methods. Results linear regression models adjusted for race gender, total stress, adult independently predicted based GrimAge faster pace DunedinPace. Associations attenuated after adjusting smoking status. sex-stratified analyses, greater associated among women but not men. No associations noted telomere length. Conclusions We found that cumulative differences by sex (e.g., women). Further research this association large diverse samples is needed.

Language: Английский

Citations

5

No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state DOI Creative Commons
S.E.P. Bruzzone,

B. Ozenne,

Patrick M. Fisher

et al.

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 27, 2024

Abstract Background Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little known about the association between this peripheral epigenetic modification brain serotonergic architecture. Here, we evaluated whole-blood-derived four CpG sites serotonin transporter ( SLC6A4 ) six tryptophan hydroxylase 2 TPH2 gene in-vivo levels (5-HTT) 4 receptor (5-HT cohort healthy individuals N = 254) and, for 5-HT 4, unmedicated patients with depression 90). To do so, quantified / using bisulfite pyrosequencing estimated 5-HTT positron emission tomography. In addition, explored measures early life recent symptoms on 297 individuals. Results We found no statistically significant markers neurotransmission or although CpG2 (chr17:30,236,083) was marginally associated parental bonding inventory overprotection score cohort, statistical significance did not remain after accounting cell heterogeneity. Conclusions suggest that findings context features should be interpreted caution. More studies are needed to rule out role biomarkers

Language: Английский

Citations

4

CelFiE-ISH: a probabilistic model for multi-cell type deconvolution from single-molecule DNA methylation haplotypes DOI Creative Commons
Irene Unterman,

Dana Avrahami,

Efrat Katsman

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 10, 2024

Language: Английский

Citations

4

Biological aging of different blood cell types DOI Creative Commons
Saara Marttila, Sonja Rajić, Joanna Ciantar

et al.

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

Published: July 26, 2024

Abstract Biological age (BA) captures detrimental age-related changes. The best-known and most-used BA indicators include DNA methylation–based epigenetic clocks telomere length (TL). most common biological sample material for epidemiological aging studies, whole blood, is composed of different cell types. We aimed to compare differences in BAs between blood types assessed the indicators’ type-specific associations with chronological (CA). An analysis indicators, including TL, methylation level at cg16867657 ELOVL2 , as well Hannum, Horvath, DNAmPhenoAge, DunedinPACE clocks, was performed on 428 samples 12 values were majority pairwise comparisons types, comparison ( p < 0.05). DNAmPhenoAge showed largest type differences, up 44.5 years methylation-based TL lowest differences. T cells generally had "youngest" values, across subsets, whereas monocytes "oldest" values. All except DunedinPACE, strongly correlated CA within a type. Some such DNAmPhenoAge-difference naïve CD4 + constant regardless donor's (range 20–80 years), while they not. In conclusion, exhibit type–specific characteristics. Our results have implications understanding molecular mechanisms underlying underscore importance considering composition when utilizing them success interventions.

Language: Английский

Citations

4