Infant DNA methylation and caregiving

This 2019 US human study attempted to replicate findings of animal studies that associated caregiver behavior with infant DNA methylation of the glucocorticoid receptor gene:

“Greater levels of maternal responsiveness and appropriate touch were related to less DNA methylation of specific regions in NR3c1 exon 1F, but only for females. There was no association with maternal responsiveness and appropriate touch or DNA methylation of NR3c1 exon 1F on prestress cortisol or cortisol reactivity. Our results are discussed in relation to programming models that implicate maternal care as an important factor in programing infant stress reactivity.”


The study had many undisclosed and a few disclosed limitations, one of which was:

“Our free-play session, while consistent with the length of free-play sessions in other studies, was short (5 min). It is unclear whether a longer length of time would have yielded significant different maternal responsiveness and appropriate touch data.”

The final sentence showed the study’s purpose was other than discovering factual evidence:

“Following replication of this work, it could ultimately be used in conjunction with early intervention, or home-visiting programs, to measure the strength of the intervention effect at the epigenetic level.”

https://onlinelibrary.wiley.com/doi/full/10.1002/imhj.21789 “DNA methylation of NR3c1 in infancy: Associations between maternal caregiving and infant sex” (not freely available)

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What drives cellular aging?

This 2019 US/UK human cell study by the founder of the epigenetic clock method investigated epigenetic aging:

“It is widely assumed that extension of lifespan is a result of retardation of ageing. While there is no counter-evidence to challenge this highly intuitive association, supporting empirical evidence to confirm it is not easy to acquire.

The scarcity of empirical evidence is due in part to the lack of a good measure of age that is not based on time. In this regard, the relatively recent development of epigenetic clocks is of great interest.

At the cellular level more is known, but from the perspective of what epigenetic ageing is not, rather than what it is. While we still do not know what cellular feature is associated with epigenetic ageing, we can now remove:

  • somatic cell differentiation

from the list of possibilities and place it with

  • cellular senescence,
  • proliferation and
  • telomere length maintenance,

which represent cellular features that are all not linked to epigenetic ageing.”


The study used several agents, including rapamycin, to investigate the hypotheses. Rapamycin isn’t a panacea, but:

“The ability of rapamycin to suppress the progression of epigenetic ageing is very encouraging for many reasons not least because it provides a valuable point-of-entry into molecular pathways that are potentially associated with it. Evidently, the target of rapamycin, the mTOR complex is of particular interest.

The convergence of the GWAS observation with the experimental system described here is a testament of the strength of the skin & blood clock in uncovering biological features that are consistent between the human level and cellular level. It lends weight to the emerging view that the mTOR pathway may be the underlying mechanism that supports epigenetic ageing.”

The limitation section ended with:

“It is important to note that it is inadvisable (actively discouraged) to directly extrapolate the studies here, especially in terms of the magnitude of age suppression, to potential effects of rapamycin on humans.”

https://www.aging-us.com/article/101976/text “Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation”

Do delusions have therapeutic value?

This 2019 UK review discussed delusions, aka false beliefs about reality:

“Delusions are characterized by their behavioral manifestations and defined as irrational beliefs that compromise good functioning. In this overview paper, we ask whether delusions can be adaptive notwithstanding their negative features.

We consider different types of delusions and different ways in which they can be considered as adaptive: psychologically (e.g., by increasing wellbeing, purpose in life, intrapsychic coherence, or good functioning) and biologically (e.g., by enhancing genetic fitness).”


1) Although the review section 4 heading was Biological Adaptiveness of Delusions, the reviewers never got around to discussing the evolved roles of brain areas. One mention of evolutionary biology was:

“Delusions are biologically adaptive if, as a response to a crisis of some sort (anomalous perception or overwhelming distress), they enhance a person’s chances of reproductive success and survival by conferring systematic biological benefits.”

2) Although section 5’s heading was Psychological Adaptiveness of Delusions, the reviewers didn’t connect feelings and survival sensations as origins of beliefs (delusions) and behaviors. They had a few examples of feelings:

“Delusions of reference and delusions of grandeur can make the person feel important and worthy of admiration.”

and occasionally sniffed a clue:

“Some delusions (especially so‐called motivated delusions) play a defensive function, representing the world as the person would like it to be.”

where “motivated delusions” were later deemed in the Conclusion section to be a:

“Response to negative emotions that could otherwise become overwhelming.”

3) Feelings weren’t extensively discussed until section 6 Delusions in OCD and MDD, which gave readers the impression that feelings were best associated with those diseases.

4) In the Introduction, sections 4, 5, and 7 How Do We Establish and Measure Adaptiveness, the reviewers discussed feeling meaning in life, but without understanding:

  1. Feelings = meaning in life, as I quoted Dr. Arthur Janov in The pain societies instill into children:

    “Without feeling, life becomes empty and sterile. It, above all, loses its meaning.

  2. Beliefs (delusions) defend against feelings.
  3. Consequentially, the stronger and more numerous beliefs (delusions) a person has, the less they feel meaning in life.

5) Where, when, why, and how do beliefs (delusions) arise? Where, when, why, and how does a person sense and feel, and what are the connections with beliefs (delusions)?

The word “sense” was used 29 times in contexts such as “make sense” and “sense of [anxiety, coherence, control, meaning, purpose, rational agency, reality, self, uncertainty]” but no framework connected biological sensing to delusions. Papers from other fields have detailed cause-and-effect explanations and diagrams for every step of precursor-successor processes.


Regarding the therapeutic value of someone else’s opinion of a patient’s delusions – I’ll reuse this quotation from the Scientific evidence page of Dr. Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” p.166:

“Primal Therapy differs from other forms of treatment in that the patient is himself a therapist of sorts. Equipped with the insights of his history, he learns how to access himself and how to feel.

The therapist does not heal him; the therapist is only the catalyst allowing the healing forces to take place. The patient has the power to heal himself.

Another way Dr. Janov wrote this was on p.58 of his 2016 book Beyond Belief as quoted in Beyond Belief: The impact of merciless beatings on beliefs:

No one has the answer to life’s questions but you. How you should lead your life depends on you, not outside counsel.

We do not direct patients, nor dispense wisdom upon them. We have only to put them in touch with themselves; the rest is up to them.

Everything the patient has to learn already resides inside. The patient can make herself conscious. No one else can.”

https://onlinelibrary.wiley.com/doi/full/10.1002/wcs.1502 “Are clinical delusions adaptive?”

Another important transgenerational epigenetic inheritance study

This 2019 Washington State University rodent study from Dr. Michael Skinner’s lab found:

“A cascade of epigenetic alterations initiated in the PGCs [primordial germ cells] appears to be required to alter the epigenetic programming during spermatogenesis to modify the sperm epigenome involved in the transgenerational epigenetic inheritance phenomenon.

Following fertilization there is a DNA methylation erasure to generate the stem cells in the early embryo, which then remethylate in a cell type-specific manner. The DNA methylation erasure is thought to, in part, reset deleterious epigenetics in the germline. However, imprinted gene DNA methylation sites and induced transgenerational epimutations appear to be protected from this DNA methylation erasure.

A germline with an altered epigenome has the capacity to alter the early embryo’s stem cell’s epigenome and transcriptome that can subsequently impact the epigenomes and transcriptomes of all derived somatic cells. Therefore, an altered sperm epigenome has the capacity to transmit phenotypes transgenerationally. Experiments have demonstrated that epigenetic inheritance can also be transmitted through the female germline.

Previously, the agricultural fungicide vinclozolin was found to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate the developmental origins of the transgenerational DMRs during gametogenesis.

The current study with vinclozolin-induced transgenerational inheritance demonstrates that sperm DMRs also originate during both spermatogenesis and earlier stages of germline development, but at distinct developmental stages. This is a genome-wide analysis of epigenetic programming during gametogenesis for transgenerational sperm epimutations.”


The study’s main hypotheses were:

Following fertilization, the hypothesis is that the transgenerational epimutations modify early embryonic transcriptomes and epigenomes to re-establish the cascade for the next generation.

As the individual develops, all somatic cells have altered epigenomes and transcriptomes to promote disease susceptibility later in life.

Researchers: adopt these hypotheses, and don’t limit your study designs to the F1 children as did:

Don’t stop at the F2 grandchildren like:

Continue studies on to F3 descendants who had no direct exposure to the altering stimulus. Keep in the forefront of your research proposals that there are probably more than 10,000,000 F3 great-grandchildren of DES-exposed women just in the US.

https://www.tandfonline.com/doi/pdf/10.1080/15592294.2019.1614417?needAccess=true “Transgenerational sperm DNA methylation epimutation developmental origins following ancestral vinclozolin exposure”

The transgenerational impact of Roundup exposure

The latest 2019 Washington State University rodent study from Dr. Michael Skinner’s lab found adverse effects in the grand-offspring and great-grand-offspring following their ancestor’s exposure during pregnancy to the world’s most commonly used herbicide:

“Using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology. In contrast, dramatic increases in pathologies in the F2 generation grand-offspring, and F3 transgenerational great-grand-offspring were observed.

The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities:

  1. Prostate disease in approximately 30% of F3 generation glyphosate lineage males, a three-fold increase in disease rate over controls.
  2. A transgenerational (F3 generation) obese phenotype was observed in approximately 40% of the glyphosate lineage females and 42% of the glyphosate lineage males.
  3. An increased incidence of kidney disease observed in the F3 generation glyphosate lineage females affecting nearly 40% of females.
  4. A significant increase in ovarian disease observed in the F2 [48% vs. 21% for controls] and F3 [36% vs. 15% for controls] generation glyphosate lineage females.
  5. During the gestation of F2 generation mothers with the F3 generation fetuses, dramatic parturition abnormalities were observed in the glyphosate lineage. The frequency of unsuccessful parturition was 35%. To further investigate the parturition abnormalities an outcross of F3 generation glyphosate lineage males with a wildtype female was performed. There were parturition abnormalities observed with a frequency of 30%.

Classic and current toxicology studies only involve direct exposure of the individual, while impacts on future generations are not assessed. The ability of glyphosate and other environmental toxicants to impact our future generations needs to be considered, and is potentially as important as the direct exposure toxicology done today for risk assessment.”


Why isn’t coverage of this study the top story of the world’s news organizations? Is what’s reported more important than reliable evidence of generational consequences to environmental experiences?

Current toxicology practices are a scientific disgrace:

  • What are the hypotheses of practices that only test effects on somatic cells, that don’t look for generational effects of germ cell modifications?
  • Are they selected for their relative convenience instead of chosen for their efficacy?

Why don’t sponsors fund and researchers perform human studies of transgenerational epigenetic inheritance? For example, from Burying human transgenerational epigenetic evidence:

“From the late 1930s through the early 1970s, DES was given to nearly two million pregnant women in the US alone.

Fourth [F3] generation effects of prenatal exposures in humans have not been reported.

Zero studies of probably more than 10,000,000 F3 great-grandchildren of DES-exposed women just here in the US!

There will be abundant human evidence to discover if sponsors and researchers will take their fields seriously.

https://www.nature.com/articles/s41598-019-42860-0.pdf “Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology”

Non-emotional memories

This 2019 US review covered memory mechanisms:

“With memory encoding reliant on persistent changes in the properties of synapses, a key question is how can memories be maintained from days to months or a lifetime given molecular turnover? It is likely that positive feedback loops are necessary to persistently maintain the strength of synapses that participate in encoding.

These levels are not isolated, but linked by shared components of feedback loops.”


Despite the review’s exhaustive discussion, the reviewers never came to the point. The word cloud I made of the review’s most frequent thirty words had little to do with why memory occurs.

Why do some stimuli evoke a memory in response? Why are almost all of the stimuli an organism receives not remembered?

Much of the discussion was baseless because it excluded emotion. Many of the citations’ memory findings relied on emotion, though. For example, in the subsection Roles of persistent epigenetic modifications for maintaining LTF [long-term facilitation], LTP [long-term potentiation], and LTM [long-term memory]:

  • Histone acetylation is increased after fear conditioning in the hippocampus and amygdala.
  • Correspondingly, inhibition of histone deacetylase enhances fear conditioning and LTP.
  • Following fear conditioning, histone phosphorylation is also increased.
  • DNA methylation is also up-regulated in the hippocampus and amygdala after fear conditioning, and inhibition of DNA methylation blocks fear LTM.”

http://learnmem.cshlp.org/content/26/5/133.full “How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory”

Why do we believe obvious lies?

Here are two accounts of this weekend’s news from real journalists, neither of whom are fans of the current US president.

Matt Taibbi of Rolling Stone
https://taibbi.substack.com/p/russiagate-is-wmd-times-a-million
“It’s official: Russiagate is this generation’s WMD”

He cited intentional misreporting (lying) multiple times from the New York Times, Washington Post, CNN, Wall Street Journal, MSNBC, Mother Jones; and from NBC, ABC, McClatchy, New Yorker, New York Magazine, Bloomberg, BuzzFeed, Slate, Yahoo, Fortune, Guardian; and from numerous US congressmen and senators. Most of these false stories have still not yet been corrected or retracted.

  • “Recapping: the reporter who introduced Steele to the world (his September 23, 2016 story was the first to reference him as a source), who wrote a book that even he concedes was seen as “validating” the pee tape story, suddenly backtracks and says the whole thing may have been based on a Las Vegas strip act, but it doesn’t matter because Stormy Daniels, etc.
  • When explosive #Russiagate headlines go sideways, the original outlets simply ignore the new development, leaving the “retraction” process to conservative outlets that don’t reach the original audiences.
  • The Russiagate era has so degraded journalism that even once “reputable” outlets are now only about as right as politicians, which is to say barely ever, and then only by accident.
  • Authorities have been lying their faces off to reporters since before electricity! It doesn’t take much investigation to realize the main institutional sources in the Russiagate mess – the security services, mainly – have extensive records of deceiving the media.
  • As noted before, from World War I-era tales of striking union workers being German agents to the “missile gap” that wasn’t (the “gap” was leaked to the press before the Soviets had even one operational ICBM) to the Gulf of Tonkin mess to all the smears of people like Martin Luther King, it’s a wonder newspapers listen to whispers from government sources at all.”


Glenn Greenwald of The Intercept
https://twitter.com/ggreenwald

  1. “Can’t the people who got rich exploiting liberal #Resistance fears by feeding them false conspiracies at least content themselves to their bulging bank accounts from the scam they pulled off & have one day of silence where they don’t try to pretend that they were right all along?
  2. If you’re just going to let stuff like this go – unexamined, unacknowledged, and unaccounted for – don’t expect anyone to be remotely sympathetic to the fact that public trust in big media is nonexistent and politicians benefit by making journalists their enemies.
  3. And just for future reference: documenting the falsehoods, baseless conspiracies, and deceitful narratives being peddled without dissent by the major corporate media isn’t “blogging” or “media criticism.” It’s journalism. It’s reporting. And it’s vital.
  4. Nothing kills journalism worse than cowardly group-think, and it’s worse than ever since they’re congregated in the same places in Brooklyn and the West Coast and petrified of saying anything that makes them unpopular among their peers.
  5. Check every MSNBC personality, CNN law “expert,” liberal-centrist outlets and #Resistance scam artist and see if you see even an iota of self-reflection, humility or admission of massive error.
  6. I wrote this with @GGreenwald in November 2016, warning Russiagate was being used to attack, smear, and censor alternative media. Those blacklisted alternative media ended up being correct about Russiagate – while the corporate media spread actual fake news.
  7. There should be major accountability in the US media and in the intelligence community they united with to drown US political discourse for 2 years straight in unhinged conspiratorial trash, distracting from real issues. That’s what should happen as a first step. But it won’t.”