DNA methylation

The degree of epigenetic DNA methylation may be used as a proxy to measure biological age

gettingwell4 4-5 stars Advanced knowledge, Epigenetics

This fascinating 2014 human study developed the new use of a somewhat intuitive marker of aging. The researchers used the degree of methylation – an epigenetic chemical modification of DNA – as an epigenetic clock to measure biological age.

The researchers found that, on average, the epigenetic age of the liver increased by 3.3 years for every increase in 10 body mass index (BMI) units. Other studied tissue areas weren’t similarly affected.

http://www.pnas.org/content/111/43/15538.full “Obesity accelerates epigenetic aging of human liver”

If rodent training had beneficial epigenetic effects, how can the next step be human gene therapy?

gettingwell4 0-1 star Wasted resources, Epigenetics, Memory , ,

This 2014 rodent study detailed significant and lasting epigenetic DNA methylation in the hippocampus part of the limbic system as a result of fear-extinction training.

The researchers missed the boat when explaining in interviews how their research could apply to humans. What I understood from the interviews was that the researchers were focused on targeting human genes with some outside action.

Recommending human gene therapy smelled like an agenda. If these epigenetic modifications were induced by training in rodents, wouldn’t the next step be research into reversal training or therapeutic activity for humans?

The researchers also found:

“Importantly, these effects were specific to extinction training and did not occur in mice that had been fear conditioned, followed by a single reactivation trial, therefore arguing against the possibility that such epigenetic modifications are nonspecifically induced by the retrieval or reconsolidation of the original fear memory.”

This was fine for rodent studies where the origins of both the disease and the cure were all exerted externally. I didn’t see that it necessarily applied to humans.

After all, we’re not lab rats. We can perform effective therapy that doesn’t involve some outside action being done to us.

http://www.pnas.org/content/111/19/7120.full “Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation”

Are stress-induced epigenetic changes to DNA inherited across generations?

gettingwell4 0-1 star Wasted resources, Amygdala, Brain development, Cortisol, Epigenetics, Limbic system, Memory, Neurochemicals, Stress , , , , ,

This 2014 Geneva/Cambridge plant study ended by stating:

“The unequivocal demonstration of transgenerational transmission of environmentally-induced epigenetic traits remains a significant challenge.

One of the critical activities erasing stress memories is conserved between plants and mammals.”

However, the researchers didn’t demonstrate that their findings were broadly applicable for mammals or organisms other than the specific plant variety they studied. Possible reasons for these limited findings were given in a 2015 Australian study referenced by Mechanisms of stress memories in plants:

“The majority of DNA methylation analyses performed in plants to date have focused on Arabidopsis, despite being relatively depleted of TEs [transposable elements] (15–20% of the genome) and being poorly methylated compared to other plant genomes.

These studies have lacked the resolution to provide the specific context and genomic location of the changes in DNA methylation.”

There are also significant differences in how epigenetic inheritance across generations may operate among different species per Epigenetic reprogramming in plant and animal development.

Neither the current study nor the above review addressed the behavioral aspect of stress-induced epigenetic inheritance across generations. For example, the behavior of a mother whose DNA was epigenetically changed by stress can induce the same epigenetic changes to her child’s DNA when her child is stressed per One way that mothers cause fear and emotional trauma in their infants:

“Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups’ stress response paired with the cue to induce amygdala-dependent learning plasticity.”

http://www.pnas.org/content/111/23/8547.full “Identification of genes preventing transgenerational transmission of stress-induced epigenetic states”

DNA methylation is the most frequent way that duplicate genes are epigenetically silenced

gettingwell4 2-3 stars Required further work, Epigenetics

This 2014 human study showed that DNA methylation was the most frequent way that duplicate genes were epigenetically silenced. Current thinking is that at least half of the genes in the human genome are inactive duplicates.

The study stated:

“Duplicate genes are essential and ongoing sources of genetic material.”

What the researchers didn’t show, however, was that duplicate genes evolve per the study’s title “evolution of duplicate genes.” It was misleading to imply in the study’s headline that duplicate genes evolve.

Evolution occurs as organisms adapt to their environments. Duplicate genes aren’t active in the adaptation process when they are silenced.

http://www.pnas.org/content/111/16/5932.full “DNA methylation and evolution of duplicate genes”

Non-PC alert: Treating the mother’s obesity symptoms positively affects the post-surgery offspring

gettingwell4 4-5 stars Advanced knowledge, Epigenetics , ,

This 2013 Quebec human epigenetic study found that DNA methylation – chemical modification that causes genes to express differently – as durably detectable between siblings born before and after their mother’s gastric bypass surgery.

The younger, post-maternal-surgery siblings were found to have DNA indicating reduced risks of developing diabetes and heart disease when compared with the DNA of their older, pre-maternal-surgery siblings. The mothers’ average weight loss was 103 lbs.

It was notable to see this famous research reference cited:

“Prenatal exposure to famine during the Dutch hunger winter of 1944 is associated with obesity with less DNA methylation (“undermethylation”) of the imprinted insulin-like growth factor 2 (IGF2) gene in exposed offspring relative to their unexposed siblings.”

It was also notable to see the reactions to this non-politically-correct finding. For one example, this news article was in full-fledged denial, stating:

“Nor do investigators know whether a father’s weight loss might have a similar impact. It’s also possible that epigenetic inheritance wasn’t at play.”

Other news coverage expressed the memes that:

  • Pregnant women can abuse anything and everything with impunity without any consequent damage to their fetus, and
  • There wasn’t the tiniest chance that the mother was involved in any of their child’s adverse outcomes. When the child’s diverted developmental and behavioral consequences manifested, political correctness would dictate that these arose out of some unknown factors.

http://www.pnas.org/content/110/28/11439.full “Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery”

Treating the father’s symptoms of an inherited disease can epigenetically treat the son

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics , , ,

This 2014 La Jolla rodent study showed that treating the symptoms of an inherited disease can, through epigenetic DNA methylation, positively treat the symptoms in the subjects’ offspring.

The disease studied was Huntington’s, which is the most common inherited neurodegenerative disease:

  • The treatment induced epigenetic changes in the expression of genes on the male Y chromosome.
  • The treated male subjects were bred, and their sperm carried both the Huntington’s disease and the epigenetic changes that reduced the symptoms.
  • The male offspring showed both delayed onsets of Huntington’s disease and reductions of specific symptoms when compared with both the treated subjects’ female offspring and the control group non-treated subjects’ male offspring.

Per the definitions in A review of epigenetic transgenerational inheritance of reproductive disease and Transgenerational effects of early environmental insults on aging and disease, for the term in the study’s title “transgenerational effects” to apply, the researchers needed to provide evidence in at least the next 2 male and/or 3 female generations of:

“Altered epigenetic information between generations in the absence of continued environmental exposure.”

The study instead provided evidence for intergenerational effects.

http://www.pnas.org/content/112/1/E56.full “HDAC inhibition imparts beneficial transgenerational effects in Huntington’s disease mice via altered DNA and histone methylation”

Conserved epigenetic sensitivity to early life experience in the hippocampus

gettingwell4 2-3 stars Required further work, Brain development, Epigenetics, Hippocampus, Limbic system, Stress ,

This 2012 human study was done by McGill University, whose researchers in Canada are at the forefront of epigenetic studies. The subject was epigenetic DNA methylation in the hippocampus of people who experienced abuse as children and who also committed suicide.

Comparisons were made with rats that were stressed in early life to identify genomic regions that are epigenetically changeable in response to a range of early life experiences.

http://www.pnas.org/content/109/Supplement_2/17266.full “Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus”