Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus

Chouliaras, Leonidas; Hove, Daniël L.A. van den; Kenis, Günter; Cruz, J. Dela; Lemmens, Marijke A.M.; Os, Jim van; Steinbusch, Harry W.M.; Schmitz, Christoph; Rutten, Bart P. F.

doi:10.1016/j.bbi.2010.11.016

Cited by 77 publications

(94 citation statements)

References 77 publications

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“…61 A recent paper found that Dnmt3a-immunoreactivity DNA METHYLATION IN AGING AND DISEASEincreases with age in the CA3 and CA1-2 hippocampal regions of mice and that reducing caloric intake by 50% attenuates this increase. 62 An age-related increase in 5mC occurs in these regions as well as the hippocampal dentate gyrus and is also attenuated by CR. 63 Similarly, 5hmC content increases with age in all three of these regions, and CR opposes this age-related increase in the CA3 region, further implicating methylomics in hippocampal aging.…”

Section: Caloric Restrictionmentioning

confidence: 99%

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Johnson

Akman²,

Calimport³

et al. 2012

Rejuvenation Research

307

218

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DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

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Section: Caloric Restrictionmentioning

confidence: 99%

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Johnson

Akman²,

Calimport³

et al. 2012

Rejuvenation Research

307

218

View full text Add to dashboard Cite

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“…107 In mice, CR is able to limit the increase in Dnmt3a levels that normally occurs in aging cells. 108,109 Thus, nutrition and growth signaling both affect aging, mediated at least in part by heterochromatin redistribution. Regulation, of the expression of genes involved in metabolism, apoptosis and cellular senescence by increased local facultative heterochromatinization may be an important mechanism by which aging is regulated.…”

Section: Global Heterochromatin Lossmentioning

confidence: 99%

Global heterochromatin loss

Tsurumi

2012

Epigenetics

182

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“…Another large scale study using human brain tissue identified CpG loci, primarily CpG islands, with consistent positive correlation between DNA methylation, and chronological age [23]. In addition, recent findings on an aging mouse cohort kept under controlled environmental conditions throughout live showed that the level of the major de novo methylation enzyme Dnmt3a increased with age in the hippocampus [24], and correlated with age-related increase in levels of 5-methyl cytidine (5-mC). The same study showed that caloric restriction, which increases lifespan and prevents age-related alterations and pathology in various animal species [25][26][27][28], was able to prevent these age-related changes in hippocampal levels of Dnmt3a [24] and 5-mC (Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction [29].…”

Section: Epigenetics and Agingmentioning

confidence: 99%

“…In addition, recent findings on an aging mouse cohort kept under controlled environmental conditions throughout live showed that the level of the major de novo methylation enzyme Dnmt3a increased with age in the hippocampus [24], and correlated with age-related increase in levels of 5-methyl cytidine (5-mC). The same study showed that caloric restriction, which increases lifespan and prevents age-related alterations and pathology in various animal species [25][26][27][28], was able to prevent these age-related changes in hippocampal levels of Dnmt3a [24] and 5-mC (Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction [29]. The speculation of a causal involvement of epigenetic mechanisms in age-related decline of functional abilities of the brain [30] is in line with i) findings that age-related memory disturbances in mice are associated with altered chromatin plasticity (in particular with dysregulation of H4k12ac) in the hippocampus [31], and ii) the link between sirtuins, i.e.…”

Section: Epigenetics and Agingmentioning

confidence: 99%

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

Pishva

Kenis

Lesch

et al. 2012

Translational Neuroscience

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Introductiondifferential epigenetic profiles) for epigenetic involvement in the most prevalent and severe psychiatric illnesses. We will end the article by discussing current research challenges in epigenetic epidemiology and neuroscience, and we propose that more studies combining epidemiological and neuroscience approaches in studying epigenetics are needed to improve our understanding of the role of the epigenetic machinery in the etiologies of psychiatric disorders. Besides robust changes in reprogramming of genomic methylation patterns in germline cells as well as in pre-implantation embryos [78]. In autism, a 10-year increase in paternal age (independent of maternal age) was associated with a 22% increased risk for autism (independent of paternal age) while a 10-year increase in maternal age has been associated with a 38% increased risk for developing the disorder [78,79], which is in line with other findings reporting associations between parental ages and autism [80][81][82]. A recent metaanalysis on the association between paternal age and schizophrenia reported that both advanced paternal age (>/=30) and younger paternal age (<25) may increase the risk of schizophrenia, with further analyses indicating that younger paternal age may be associated with particularly an increased risk in male but not female offspring [83]. Given these effects of paternal (and maternal age) on risk of several psychiatric disorders, one could speculate that Epigenetic mechanisms Epigenetics and sex differences in psychiatric disorders Environmental epigenetic in psychiatric disordersA wealth of epidemiologic evidence indicates that environmental exposures influence susceptibility to disease in later life [19,49].

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Caloric restriction attenuates age-related changes of DNA methyltransferase 3a in mouse hippocampus

Cited by 77 publications

References 77 publications

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

The Role of DNA Methylation in Aging, Rejuvenation, and Age-Related Disease

Global heterochromatin loss

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

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