scholarly journals 115.2 Impact of Fetal Gene Expression on Cortical Thickness in Young Adults

2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S60-S61
Author(s):  
Joshua Roffman ◽  
Thomas Soare ◽  
Hamdi Eryilmaz ◽  
Anais Rodriguez-Thompson ◽  
Phil Lee ◽  
...  
2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.


Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Xiaoling Wang ◽  
Yue Pan ◽  
Haidong Zhu ◽  
Guang Hao ◽  
Xin Wang ◽  
...  

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.


2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S162-S162
Author(s):  
Dana Allswede ◽  
Amanda Zheutlin ◽  
Yoonho Chung ◽  
Kevin Anderson ◽  
Christina Hultman ◽  
...  

SLEEP ◽  
2018 ◽  
Vol 41 (suppl_1) ◽  
pp. A96-A97
Author(s):  
J Y Hwang ◽  
M S Byun ◽  
Y M Choe ◽  
J H Lee ◽  
D Yi ◽  
...  

NeuroImage ◽  
2019 ◽  
Vol 189 ◽  
pp. 896-903 ◽  
Author(s):  
Christopher M. Weise ◽  
Tobias Bachmann ◽  
Matthias L. Schroeter ◽  
Dorothee Saur

2017 ◽  
Vol 43 (3) ◽  
pp. 525-533 ◽  
Author(s):  
Dana M Allswede ◽  
Amanda B Zheutlin ◽  
Yoonho Chung ◽  
Kevin Anderson ◽  
Christina M Hultman ◽  
...  

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 938-938
Author(s):  
Jaapna Dhillon ◽  
Jose Godoy-Lugo ◽  
Rudy Ortiz

Abstract Objectives This study explored the effects of diet-induced (almonds vs. crackers) changes on blood transcriptome profiles of young adults. Methods Young adults (age: 18–22 years) were randomly assigned to consume either almonds (2 oz./d, n = 13) or an isocaloric control snack of graham crackers (325 kcal/d, n = 10) daily for 4 weeks. Blood samples were collected at baseline and 4 weeks after intervention. Total leukocyte RNA was extracted and sequenced. Gene expression profiling was carried out using a 3′ Tag-RNA-Seq protocol. Barcoded sequencing libraries were prepared using the QuantSeq FWD kit for multiplexed sequencing. Data were preprocessed, STAR aligned, and count tables generated using the QuantSeq FWD-UMI pipeline. Differential expression (DE) analysis was conducted on the time x diet model using the limma-voom packages in R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the DE p-values was conducted using the Wilcoxon rank-sum test in R. P-values were adjusted for false discovery rate correction (FDR). Results Out of 13,018 filtered genes, 69 were differentially expressed (FDR &lt; 0.1). Glutamic-oxaloacetic transaminase 2 (GOT2), diacylglycerol kinase alpha (DGKA), and glutaryl-CoA dehydrogenase (GCDH) genes were upregulated with almond consumption. GOT2 plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles, DGKA is involved in lipid metabolism, and GCDH is involved in lysine degradation and tryptophan metabolism. Cracker consumption resulted in greater upregulation of TGF-beta activated kinase 1 gene (MAP3K7) binding protein 3 (TAB3) gene which is involved in the NF-kappaB signal transduction pathway and a greater downregulation in the immunoglobulin superfamily member 8 (IGSF8) gene. Enrichment analyses indicate gene annotations to 341 KEGG pathways. Thermogeneic and ribosomal pathways were significantly enriched (FDR &lt; 0.1). Pathways related to oxidative phosphorylation, sphingolipid signaling, and tryptophan, propanoate, and starch and sucrose metabolism were also differentially enriched (P &lt; 0.05, FDR &lt; 0.3). Conclusions These findings indicate that diet (almond vs cracker) potentially alters metabolism through changes in gene transcription. The implications of these findings and associations with health and disease outcomes need to be investigated further. Funding Sources NIH


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