Interleukin-6 determines protein stabilization of DNA methyltransferases and alters DNA promoter methylation of genes associated with insulin signaling and angiogenesis

Balakrishnan, Aswath; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Joshi, Manjunath B.

doi:10.1038/s41374-018-0079-7

Cited by 45 publications

(43 citation statements)

References 47 publications

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“…RPS6KA is one of the genes where the promoter DNA methylation status is linked to insulin signalling and angiogenesis. This happens through an interplay with the cytokine IL-6 and reduced levels of the methyl transferases DNMT1 and DNMT3B 50 .…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Kvaløy

Page

Holmen

2018

Sci Rep

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Knowledge of epigenetically regulated biomarkers linked to obesity development is still scarce. Improving molecular understanding of the involved factors and pathways would improve obesity phenotype characterization and reveal potentially relevant targets for obesity intervention. The Illumina Infinium HumanMethylation450 BeadChip was used in a leucocyte epigenome-wide association study (EWAS) to quantify differential DNA methylation in 60 lean compared with 60 obese young women. Replication was done in monozygotic twins discordant for obesity. At adolescence and adulthood, the two weight groups differed significantly in obesity-related traits and metabolic risk factors. Differential hypomethylation was overrepresented in obese compared to lean women. In the adjusted model, the EWAS revealed 10 differentially methylated CpG sites linked to 8 gene loci – COX6A1P2/FGD2, SBNO2, TEX41, RPS6KA2, IGHE/IGHG1/IGHD, DMAP1, SOCS3, and SETBP1– and an enhancer locus at chromosome 2 (2p25.1). The sites linked to TEX41, IGHE/IGHG1/IGHD, DMAP1, and SETBP1 were novel findings, while COX6A1P/FGD2, SBNO2, RPS6KA2, and SOCS3 had been identified previously with concordant direction of effects. RPS6KA2, DMAP1, and SETBP1 were replicated in the BMI-discordant monozygotic twin cohort using the FDR of 5%.

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Section: Discussionmentioning

confidence: 99%

Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Kvaløy

Page

Holmen

2018

Sci Rep

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“…DNA methylation has been recognized as a critical mechanism promoting senescence and ageing at the molecular and cellular levels [149][150][151][152][153]. The DNA methylome of senescent cells shows extensive hypomethylation and formation of facultative heterochromatin domains compared to proliferating normal cells.…”

Section: Epigenetics Of Ageing: a Focus On Dna Methylationmentioning

confidence: 99%

“…In particular, bisulfite sequencing analysis of the methylome in both proliferating and senescent cells revealed a decline in CpG methylation in senescent cells ranging between 65.0% and 58.4%. Notably, these hypomethylation events are enriched in the lamin-associated domains which are dynamic regions that occupy up to 40% of the genome across different cell types and lead to the establishment and preservation of transcriptional microenvironments [153].…”

Section: Epigenetics Of Ageing: a Focus On Dna Methylationmentioning

confidence: 99%

Molecular basis of ageing in chronic metabolic diseases

Spinelli

Parrillo

Longo

et al. 2020

J Endocrinol Invest

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Aim Over the last decades, the shift in age distribution towards older ages and the progressive ageing which has occurred in most populations have been paralleled by a global epidemic of obesity and its related metabolic disorders, primarily, type 2 diabetes (T2D). Dysfunction of the adipose tissue (AT) is widely recognized as a significant hallmark of the ageing process that, in turn, results in systemic metabolic alterations. These include insulin resistance, accumulation of ectopic lipids and chronic inflammation, which are responsible for an elevated risk of obesity and T2D onset associated to ageing. On the other hand, obesity and T2D, the paradigms of AT dysfunction, share many physiological characteristics with the ageing process, such as an increased burden of senescent cells and epigenetic alterations. Thus, these chronic metabolic disorders may represent a state of accelerated ageing. Materials and methods A more precise explanation of the fundamental ageing mechanisms that occur in AT and a deeper understanding of their role in the interplay between accelerated ageing and AT dysfunction can be a fundamental leap towards novel therapies that address the causes, not just the symptoms, of obesity and T2D, utilizing strategies that target either senescent cells or DNA methylation. Results In this review, we summarize the current knowledge of the pathways that lead to AT dysfunction in the chronological ageing process as well as the pathophysiology of obesity and T2D, emphasizing the critical role of cellular senescence and DNA methylation. Conclusion Finally, we highlight the need for further research focused on targeting these mechanisms.

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“…In aged mice following peripheral lipopolysaccharide (LPS), DNA methylation in IL‐1β promoter in primary microglia significantly decreased . Furthermore, interleukin‐6 is also reported to reduce DNMT1 and result in the DNA hypomethylation in the endothelia cells and B cells . However, it is still unknown whether systemic inflammation in the POCD patients is more severe than non‐POCD patients.…”

Section: Discussionmentioning

confidence: 99%

Association of global DNA hypomethylation with post‐operative cognitive dysfunction in elderly patients undergoing hip surgery

Tang

et al. 2019

Acta Anaesthesiol Scand

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Post-operative cognitive dysfunction (POCD) is a decline in cognitive status after surgery, typically manifesting as alterations in orientation, memory, thinking, attention, insight or other aspects of central nervous system function. 1 POCD can last for a few days to years and is associated with adverse effects, including increased surgical morbidity and mortality, hospitalization and out-of-hospital care costs. For patients older than 60 years-of-age, POCD occurred in 25% to 40% of patients 1 week after non-cardiac surgery. 2-4 Accumulating evidence suggests that anesthetics, surgical stress, hypo-perfusion, and inflammatory responses may contribute to the risk of POCD. 5 Recent studies also indicate that genetic factors contribute to this post-operative neurologic injury. 6,7 However, the traditional explanations are not sufficient to explain the complex interaction between POCD, environment, and genetics.Epigenetic modification emerges as an important mechanism of regulating gene-environment interaction, and its critical function in Background: Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear.Methods: Subjects (N = 124) older than 65 years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI < −1.96.Peripheral leukocyte DNA was isolated, and DNA methylation was measured via 5-methylcytosine (mC) using Elisa. Results:Twenty-four patients (19.4%) developed early POCD. There was no difference in baseline 5-mC levels by POCD status. The 5-mC levels significantly decreased on day 7 after surgery in patients who developed early POCD (P = .004), but did not change in non-POCD patients. Moreover, post-operative 5-mC levels were significantly lower in POCD patients than those in non-POCD patients (P = .003). Bivariate logistic models adjusted for age, gender, BMI, duration of anesthesia, and education level clearly demonstrated an independent association between post-operative 5-mC level and early POCD. Conclusions:Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. Trial registration: ClinicalTrial, NCT02965235. Registered 16 November 2016, https ://www.clini caltr ials.gov/ct2/resul ts?term=NCT02 96523 5&rank=1#rowId0

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Interleukin-6 determines protein stabilization of DNA methyltransferases and alters DNA promoter methylation of genes associated with insulin signaling and angiogenesis

Cited by 45 publications

References 47 publications

Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Epigenome-wide methylation differences in a group of lean and obese women – A HUNT Study

Molecular basis of ageing in chronic metabolic diseases

Association of global DNA hypomethylation with post‐operative cognitive dysfunction in elderly patients undergoing hip surgery

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