scholarly journals Folate supplementation increases genomic DNA methylation in the liver of elder rats

2005 ◽  
Vol 93 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Sang-Woon Choi ◽  
Simonetta Friso ◽  
Mary K. Keyes ◽  
Joel B. Mason

The availability of folate is implicated as a determinant of DNA methylation, a functionally important feature of DNA. Nevertheless, when this phenomenon has been examined in the rodent model, the effect has not always been observed. Several reasons have been postulated for the inconsistency between studies: the rodent is less dependent on folate as a methyl source than man; juvenile animals, which most studies use, are more resistant to folate depletion than old animals; methods to measure genomic DNA methylation might not be sensitive enough to detect differences. We therefore examined the relationship between folate and genomic DNA methylation in an elder rat model with a newly developed method that can measure genomic DNA methylation sensitively and precisely. Thirty-nine 1-year-old rats were divided into three groups and fed a diet containing 0, 4·5 or 18 μmol folate/kg (folate-deplete, -replete and -supplemented groups, respectively). Rats were killed at 8 and 20 weeks. At both time points, mean liver folate concentrations increased incrementally between the folate-deplete, -replete and -supplemented rats (Pfor trend <0·001) and by 20 weeks hepatic DNA methylation also increased incrementally between the folate-deplete, -replete and -supplemented rats (Pfor trend=0·025). At both time points folate-supplemented rats had significantly increased levels of DNA methylation compared with folate-deplete\ rats (P<0·05). There was a strong correlation between hepatic folate concentration and genomic DNA methylation in the liver (r0·48,P=0·004). In the liver of this animal model, dietary folate over a wide range of intakes modulates genomic DNA methylation.

2016 ◽  
Author(s):  
Daniel L. McCartney ◽  
Rosie M. Walker ◽  
Stewart W. Morris ◽  
Andrew M. McIntosh ◽  
David J. Porteous ◽  
...  

AbstractGenome-wide analysis of DNA methylation has now become a relatively inexpensive technique thanks to array-based methylation profiling technologies. The recently developed Illumina Infinium MethylationEPIC BeadChip interrogates methylation at over 850,000 sites across the human genome, covering 99% of RefSeq genes. This array supersedes the widely used Infinium HumanMethylation450 BeadChip, which has permitted insights into the relationship between DNA methylation and a wide range of conditions and traits. Previous research has identified issues with certain probes on both the HumanMethylation450 BeadChip and its predecessor, the Infinium HumanMethylation27 BeadChip, which were predicted to affect array performance. These issues concerned probe-binding specificity and the presence of polymorphisms at target sites. Using in silico methods, we have identified probes on the Infinium MethylationEPIC BeadChip that are predicted to (i) measure methylation at polymorphic sites and (ii) hybridise to multiple genomic regions. We intend these resources to be used for quality control procedures when analysing data derived from this platform.


2011 ◽  
Vol 105 (5) ◽  
pp. 688-693 ◽  
Author(s):  
Kyong-Chol Kim ◽  
Hyeran Jang ◽  
Julia Sauer ◽  
Ella M. Zimmerly ◽  
Zhenhua Liu ◽  
...  

High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C57BL/6 mice were pair-fed with four different amino acid-defined diets for 20 weeks: folate deplete (0 mg/kg diet); folate replete (2 mg/kg diet); folate supplemented (8 mg/kg diet); folate deplete (0 mg/kg diet) with thymidine supplementation (1·8 g/kg diet). Thymidylate synthesis from uracil requires folate, but synthesis from thymidine is folate independent. Liver folate concentrations were determined by the Lactobacillus casei assay. Uracil misincorporation into DNA was measured by a GC/MS method. Liver folate concentrations demonstrated a stepwise increase across the spectrum of dietary folate levels in both old (P = 0·003) and young (P < 0·001) mice. Uracil content in colonic DNA was paradoxically increased in parallel with increasing dietary folate among the young mice (P trend = 0·033), but differences were not observed in the old mice. The mean values of uracil in liver DNA, in contrast, decreased with increasing dietary folate among the old mice, but it did not reach a statistically significant level (P < 0·1). Compared with the folate-deplete group, thymidine supplementation reduced uracil misincorporation into the liver DNA of aged mice (P = 0·026). The present study suggests that the effects of folate and thymidine supplementation on uracil misincorporation into DNA differ depending on age and tissue. Further studies are needed to clarify the significance of increased uracil misincorporation into colonic DNA of folate-supplemented young mice.


2010 ◽  
Vol 104 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Julia Sauer ◽  
Hyeran Jang ◽  
Ella M. Zimmerly ◽  
Kyong-chol Kim ◽  
Zhenhua Liu ◽  
...  

Older age, dietary folate and chronic alcohol consumption are important risk factors for the development of colon cancer. The present study examined the effects of ageing, folate and alcohol on genomic and p16-specific DNA methylation, and p16 expression in the murine colon. Old (aged 18 months; n 70) and young (aged 4 months; n 70) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18 % of energy), a Lieber-DeCarli diet with alcohol (18 %) and reduced folate (0·25 mg folate/l) or an isoenergetic control diet (0·5 mg folate/l) for 5 or 10 weeks. Genomic DNA methylation, p16 promoter methylation and p16 gene expression were analysed by liquid chromatography–MS, methylation-specific PCR and real-time RT-PCR, respectively. Genomic DNA methylation was lower in the colon of old mice compared with young mice (P < 0·02) at 10 weeks. Alcohol consumption did not alter genomic DNA methylation in the old mouse colon, whereas it tended to decrease genomic DNA methylation in young mice (P = 0·08). p16 Promoter methylation and expression were higher in the old mouse colon compared with the corresponding young groups. There was a positive correlation between p16 promoter methylation and p16 expression in the old mouse colon (P < 0·02). In young mice the combination of alcohol and reduced dietary folate led to significantly decreased p16 expression compared with the control group (P < 0·02). In conclusion, ageing and chronic alcohol consumption alter genomic DNA methylation, p16 promoter methylation and p16 gene expression in the mouse colon, and dietary folate availability can further modify the relationship with alcohol in the young mouse.


Epigenomics ◽  
2021 ◽  
Author(s):  
Camila M Loureiro ◽  
Helene A Fachim ◽  
Fabiana Corsi-Zuelli ◽  
Rosana Shuhama ◽  
Paulo R Menezes ◽  
...  

Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials & methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results: GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls.


Author(s):  
Sang-Woon Choi ◽  
Simonetta Friso

AbstractInadequate folate intake and aging are each strongly implicated as important risk factors for certain cancers. Since both folate depletion and aging are strongly associated with hyperhomocysteinemia, genomic DNA hypomethylation, and increased uracil misincorporation into DNA, it appears that each of them enhances carcinogenesis by inducing a derangement of one-carbon metabolism that supplies one-carbons to biological methylation reactions and nucleotide synthesis. Recent studies have demonstrated that inadequate dietary folate and aging may interact and synergistically disturb the normal homeostasis of one-carbon metabolism, thereby provoking subsequent biochemical and molecular aberrations, including alterations in critical gene expression related to carcinogenesis. These studies have further indicated that modest folate supplementation may reverse or partially ameliorate those adverse effects induced by folate depletion and aging.


2008 ◽  
pp. 61-76
Author(s):  
A. Porshakov ◽  
A. Ponomarenko

The role of monetary factor in generating inflationary processes in Russia has stimulated various debates in social and scientific circles for a relatively long time. The authors show that identification of the specificity of relationship between money and inflation requires a complex approach based on statistical modeling and involving a wide range of indicators relevant for the price changes in the economy. As a result a model of inflation for Russia implying the decomposition of inflation dynamics into demand-side and supply-side factors is suggested. The main conclusion drawn is that during the recent years the volume of inflationary pressures in the Russian economy has been determined by the deviation of money supply from money demand, rather than by money supply alone. At the same time, monetary factor has a long-run spread over time impact on inflation.


2013 ◽  
Vol 37 (10) ◽  
pp. 1460 ◽  
Author(s):  
Huaping ZHU ◽  
Maixin LU ◽  
Zhanghan HUANG ◽  
Fengying GAO ◽  
Xiaoli KE ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 967
Author(s):  
Matthew J. Landry ◽  
Anthony Crimarco ◽  
Dalia Perelman ◽  
Lindsay R. Durand ◽  
Christina Petlura ◽  
...  

Adherence is a critical factor to consider when interpreting study results from randomized clinical trials (RCTs) comparing one diet to another, but it is frequently not reported by researchers. The purpose of this secondary analysis of the Keto–Med randomized trial was to provide a detailed examination and comparison of the adherence to the two study diets (Well Formulated Ketogenic Diet (WFKD) and Mediterranean Plus (Med-Plus)) under the two conditions: all food being provided (delivered) and all food being obtained by individual participants (self-provided). Diet was assessed at six time points including baseline (x1), week 4 of each phase when participants were receiving food deliveries (x2), week 12 of each phase when participants were preparing and providing food on their own (x2), and 12 weeks after participants completed both diet phases and were free to choose their own diet pattern (x1). The adherence scores for WFKD and Med-Plus were developed specifically for this study. Average adherence to the two diet patterns was very similar during both on-study time points of the intervention. Throughout the study, a wide range of adherence was observed among participants—for both diet types and during both the delivery phase and self-provided phase. Insight from this assessment of adherence may aid other researchers when answering the important question of how to improve behavioral adherence during dietary trials. This study is registered at clinicaltrials.gov NCT03810378.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 926
Author(s):  
Daniela M. Meléndez ◽  
Sonia Marti ◽  
Luigi Faucitano ◽  
Derek B. Haley ◽  
Timothy D. Schwinghamer ◽  
...  

Lactate is a product of anaerobic glycolysis, used in animal research as an indicator of muscle fatigue. Therefore, it has been used as an indicator of cattle response to long distance transportation. The aim of this study was to assess the relationship of L-lactate concentrations measured using a Lactate Scout+ analyzer and a traditional lactate assay colorimetric kit. Blood samples were collected by venipuncture from 96 steers (Black or Red Angus × Hereford/Simmental and Black or Red Angus × Charolais; 247 ± 38.2 kg BW) prior to loading (LO1) and after 36 h of transport, and prior to reloading and after an additional 4 h of road transportation, and on d 1, 2, 3, 5, 14, and 28 after transport. The Lactate Scout+ analyzer strip was dipped in blood at the time of sampling, while blood samples were collected into sodium fluoride tubes for use in the colorimetric analysis. Pearson correlations were calculated to assess the strength of the relationship between the experimental methods for the quantification of L-lactate concentrations. The magnitude and direction of the correlation, and the level of statistical significance varied over the observed time points, ranging from r = −0.03 (p = 0.75; LO1) to r = 0.75 (p < 0.0001; d 3). The correlation for the pooled data was weak but statistically significant (r = 0.33, p < 0.0001). Based on the low magnitude of the correlation due to variability across sampling time points in this study, the Lactate Scout+ analyzer is not a suitable alternative to a lab-based assay (considered the gold standard) for measuring L-lactate in transported cattle.


Sign in / Sign up

Export Citation Format

Share Document