Year: 2019

Would you return a lost wallet?

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The researchers in this 2019 Swiss/US study intentionally “lost” > 17,000 wallets under experimental conditions:

“We conducted field experiments in 40 countries to examine whether people act more dishonestly when they have a greater economic incentive to do so, and we found the opposite to be true. Citizens were more likely to return wallets that contained relatively larger amounts of money. Neither nonexperts nor professional economists were able to predict this result.

When people stand to heavily profit from engaging in dishonest behavior, the desire to cheat increases but so do the psychological costs of viewing oneself as a thief.”

The study did well in some aspects, including publicity. However:

1. The researchers admitted in the final paragraph:

“Using average reporting rates across countries, we find substantial variation in rates of civic honesty, ranging from 14 to 76%. This variation largely persists even when controlling for a country’s gross domestic product, suggesting that other factors besides a country’s wealth are also at play.”

Yet the paper’s first page contained the above graphic, which used each country’s GDP as a dependent variable! Wasn’t a behavioral economics study of honesty required to present their data honestly, and use factors that were experimentally significant?

2. “Other factors..at play” were relegated to the supplementary materials. The paper was only three-and-a-half pages long, so there was room for further explanations.

Here’s one comment on cultural differences from a Chinese PhD student:

“Biased design. In China (and Asian countries), people seldom use email, and our merit is to leave things untouched (“路不拾遗“:no one picks up lost articles in the street (idiom)).”

3. The study design had nothing to do with avoiding taxes, but three of the four sentences in the paper’s first paragraph did. This impressed as pointless.

https://science.sciencemag.org/content/365/6448/70 “Civic honesty around the globe” (not freely available)

Caloric restriction’s epigenetic effects

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This 2019 US review subject was caloric restriction (CR) without malnutrition:

“Cellular adaptation that occurs in response to dietary patterns can be explained by alterations in epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA. Epigenetic reprogramming of the underlying chronic low-grade inflammation by CR can lead to immuno-metabolic adaptations that enhance quality of life, extend lifespan, and delay chronic disease onset.

Short- and long-term CRs produce significant changes in different tissues and across species, in some animal models even with sex-specific effects. Early CR onset may cause a different and even an opposite effect on physiological outcomes in animal models such as body weight.”

https://academic.oup.com/advances/article-abstract/10/3/520/5420411 “Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction” (not freely available)

1. The review didn’t present evidence to equate survival (left axis) with methylation drift (right axis) per the above graphic. Methylation drift should point in the opposite direction of survival, if anything.

2. No mention was made of the epigenetic clock method of measuring age acceleration, although it’s been available since 2013 and recent diet studies have used it. The sole citation of an age acceleration study was from 2001, which was unacceptable for a review published in 2019.

3. The review provided many cellular-level details about the subject. However, organism-level areas weren’t sufficiently evidenced:

A. Arguments for an effect usually include explanations for no effect as well as for opposite effects. The reviewers didn’t provide direct evidence for why, if caloric restriction extended lifespan, caloric overabundance produced shorter lifespans.

B. Caloric restriction evidence was presented as if only it was responsible for organism-level effects. Other mechanisms may have been involved.

An example of such a mechanism was demonstrated in a 2007 rodent study Reduced Oxidant Stress and Extended Lifespan in Mice Exposed to a Low Glycotoxin Diet which compared two 40%-calorie-restricted diets.

The calories and composition of both diets were identical. However, advanced glycation end product (AGE) levels were doubled in standard chow because heating temperatures were “sufficiently high to inadvertently cause standard mouse chow to be rich in oxidant AGEs.”

The study found that a diet with lower chow heating temperatures increased lifespan and health span irrespective of caloric restriction!

  • The low-AGE calorie-restricted diet group lived an average of 15% longer (>20 human equivalent years) than the CR group.
  • 40% of the low-AGE calorie-restricted diet group were still alive when the last CR group member died.
  • The CR group also had significantly more: 1) oxidative stress damage; 2) glucose and insulin metabolism problems; and 3) kidney, spleen, and liver injuries.

A drug that countered effects of a traumatizing mother

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This 2019 US rodent study concerned transmitting poor maternal care to the next generation:

“The quality of parental care received during development profoundly influences an individual’s phenotype, including that of maternal behavior. Infant experiences with a caregiver have lifelong behavioral consequences.

Maternal behavior is a complex behavior requiring the recruitment of multiple brain regions including the nucleus accumbens, bed nucleus of the stria terminalis, ventral tegmental area, prefrontal cortex, amygdala, and medial preoptic area. Dysregulation within this circuitry can lead to altered or impaired maternal responsiveness.

We administered zebularine, a drug known to alter DNA methylation, to dams exposed during infancy to the scarcity-adversity model of low nesting resources, and then characterized the quality of their care towards their offspring.

  1. We replicate that dams with a history of maltreatment mistreat their own offspring.
  2. We show that maltreated-dams treated with zebularine exhibit lower levels of adverse care toward their offspring.
  3. We show that administration of zebularine in control dams (history of nurturing care) enhances levels of adverse care.
  4. We show altered methylation and gene expression in maltreated dams normalized by zebularine.

These findings lend support to the hypothesis that epigenetic alterations resulting from maltreatment causally relate to behavioral outcomes.

Maternal behavior is an intergenerational behavior. It is important to establish the neurobiological underpinnings of aberrant maternal behavior and explore treatments that can improve maternal behavior to prevent the perpetuation of poor maternal care across generations.”

The study authors demonstrated intergenerational epigenetic effects, and missed an opportunity to also investigate transgenerational epigenetically inherited effects. They cited reference 60 for the first part of the above quotation, but the cited reviewer misused the transgenerational term by applying it to grand-offspring instead of the great-grand-offspring.

There were resources available to replicate the study authors’ previous findings, which didn’t show anything new. Why not use such resources to uncover evidence even more applicable to humans by extending experiments to great-grand-offspring that would have no potential germline exposure to the initial damaging cause?

Could a study design similar to A limited study of parental transmission of anxiety/stress-reactive traits have been integrated? That study’s thorough removal of parental behavior would be an outstanding methodology to confirm by falsifiability whether parental behavior is both an intergenerational and a transgenerational epigenetic inheritance mechanism.

Rodent great-grand-offspring can be studied in < 9 months. It takes > 50 years for human studies to reach the great-grand-offspring transgenerational generation.

  • Why not attempt to “prevent the perpetuation of poor maternal care across generations?”
  • Isn’t it a plausible hypothesis that humans “with a history of maltreatment mistreat their own offspring?”
  • Isn’t it worth the extra effort to extend animal research to investigate this unfortunate chain?

https://www.nature.com/articles/s41598-019-46539-4 “Pharmacological manipulation of DNA methylation normalizes maternal behavior, DNA methylation, and gene expression in dams with a history of maltreatment”

Wikipedia is a poor source of information on advanced glycation end products (AGEs)

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A link to Wikipedia is usually on the first page of search results. The Wikipedia post on AGEs lacks the evidence that a reader may infer from its text.

For example, the second paragraph of the AGEs post, Dietary Sources, contained the following text and references:

  1. “However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. [4]
  2. Therefore it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. [5]
  3. This does not free diet from potentially negatively influencing AGE, but implicates dietary AGE may be less important than other aspects of diet that lead to elevated blood sugar levels and formation of AGEs. [4] [5]”

[4] https://www.sciencedirect.com/science/article/pii/S0278691513004444 “Advanced glycation end products in food and their effects on health” (not freely available) 2013 Denmark.

Please note on this linked page that a German researcher took the time to correct one bias of the Danish reviewers, citing evidence from his studies that:

“The deleterious effects of food-derived AGEs in subjects with type 2 diabetes mellitus are proven.”

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257625 “Dietary Advanced Glycation End Products and Aging” 2010 US.

Both of these references were reviews.

Unlike study researchers, reviewers aren’t bound to demonstrate evidence from tested hypotheses. Reviewers are free to:

  • Express their beliefs as facts;
  • Over/under emphasize study limitations; and
  • Disregard and misrepresent evidence as they see fit.

Reviewers also aren’t obligated to make post-publication corrections for their errors and distortions. For example, the Danes didn’t correct their review with any findings the German researcher presented.

As such, reviews can’t be cited for reliable evidence.

A sample of other problems with each of the Wikipedia sentences:

1. “However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. [4]”

The first part of sentence 1 came from the review’s abstract:

“Only LMW AGEs..may be absorbed from the gut and contribute to the body burden of AGEs.”

But the reviewers didn’t support their abstract’s statement with direct evidence from any study!

2. “Therefore it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. [5]”

The “therefore” of sentence 2 was misplaced. Sentence 1 didn’t attempt to explain whether “dietary AGEs contribute to disease and aging” or “only endogenous AGEs matter.”

Since sentence 2 wasn’t a consequence of sentence 1, the Wikipedia contributor(s) needed to support sentence 2 with evidence. Citing an “unclear” 2010 reference [5] ignored dozens of studies that provided better clarity.

3. “This does not free diet from potentially negatively influencing AGE, but implicates dietary AGE may be less important than other aspects of diet that lead to elevated blood sugar levels and formation of AGEs. [4] [5]”

Wikipedia contributors tend to cite irrelevant references rather than get flagged with “citation needed.” The value judgment of sentence 3 was an example of this intentionally misleading masquerade.

“Dietary AGE may be less important..” wasn’t unequivocally supported by studies referenced in either review, and didn’t represent an authoritative body of evidence. Contrast those weasel words with:

“The deleterious effects of food-derived AGEs in subjects with type 2 diabetes mellitus are proven.”

Good job, Wikipedia contributors! You used lower-quality reviews to promote misunderstandings that DETRACTED from science.

Wikipedia’s premise is that since the group knows more about any subject than does any individual, everyone is entitled to contribute. The results are usually incoherent narratives that often substitute opinions for evidence.

The second paragraph of the Exogenous section of the Wikipedia glycation post provided an example:

  • Assertions of the first and third sentences needed citations. Did the contributor(s) think these would be unexamined?
  • Someone contributed a cancer reference as the fourth sentence, although it had little to do with the preceding sentences.
  • The fifth sentence was informative on exogenous glycations and AGEs. An editor would have removed “recently” and “recent” though, because the cited source was dated 2005.

Disease and advanced glycation end products (AGEs)

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This 2015 French/US review focused on chronic kidney disease, appropriate for its publication in the Journal of the American Society of Nephrology:

“Advanced glycation end products (AGEs) are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. Humans are exposed to exogenous sources of AGE (diet and cigarette smoke) and endogenous sources of AGE when the organism is exposed to high levels of glucose, such as in diabetes.

Accumulation of AGEs in patients with CKD has been shown to result from inflammation, oxidative stress, and diet. AGEs are proinflammatory and pro-oxidative compounds that play a role in the high prevalence of endothelial dysfunction and subsequent cardiovascular disease in patients with CKD.

In view of the many harmful effects of AGEs on cell function, it is essential to develop strategies designed to counteract their effects. AGEs are generated during the thermal processing and storage of foods. Dietary restriction is an effective, feasible, and economic method to reduce levels of toxic AGEs and possibly, the associated cardiovascular mortality.”

https://jasn.asnjournals.org/content/27/2/354 “Uremic Toxicity of Advanced Glycation End Products in CKD”

I came across the AGE subject in the usual Internet way. 🙂 While reading comments on Josh Mitteldorf’s blog post Money in Aging Research, Part I, Dr. Alan Green mentioned Dr. Helen Vlassara’s work. A DuckDuckGo search led to her 44,256 citations, which increase every day.

Another read on the subject is her 2016 book Dr. Vlassara’s AGE-Less Diet: How a Chemical in the Foods We Eat Promotes Disease, Obesity, and Aging and the Steps We Can Take to Stop It. A practical guide is her 2017 book The AGE Food Guide: A Quick Reference to Foods and the AGEs They Contain.

A better method of measuring neurogenesis

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One of the references cited in Linking adult neurogenesis to Alzheimer’s disease was https://www.nature.com/articles/s41591-019-0375-9 “Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease” (not freely available).

This 2019 Spanish human study used improved techniques to find:

“Adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry. Direct evidence of AHN in humans has remained elusive. Determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential.

By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced.

These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.”

The control group was 13 neurologically healthy deceased people aged 43 to 87. The AD group was 45 deceased people, distributed among the six Braak stages of the pathology, aged 52 to 97.

Linking adult neurogenesis to Alzheimer’s disease

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This 2019 Spanish human study compared DNA methylation, chromatin and histone modifications in the hippocampus of deceased Alzheimer’s disease patients with controls:

“A significant percentage of the differentially methylated genes were related to neural development and neurogenesis. It was astounding that other biological, cellular, and molecular processes generally associated with neurodegeneration such as apoptosis, autophagy, inflammation, oxidative stress, and mitochondrial or lysosomal dysfunction were not overrepresented.

The results of the present study point to neurogenesis-related genes as targets of epigenetic changes in the hippocampus affected by AD. These methylation changes might be built throughout life due to external and internal cues and would represent an example of epigenetic interaction between environmental and genetic factors in developing AD.

As an alternative explanation, these epigenetic marks might also represent the trace of DNA methylation alterations induced during early developmental stages of the hippocampus, which would remain as a fingerprint in the larger proportion of hippocampal neurons that are not exchanged. This second hypothesis would link AD to early life stages, in concordance with recent studies that revealed abnormal p-tau deposits (pre-tangles) in brains of young individuals under 30, suggesting AD pathology would start earlier in life than it was previously thought. The influence of the genetic risk for AD has also been postulated to begin in early life, and other AD risk factors may be influenced by in utero environment.”

The study cited references to adult neurogenesis:

“Though strongly related to brain development, neurogenesis is also maintained in the adult human brain, mainly in two distinct areas, i.e., the subventricular zone and the subgranular zone of the dentate gyrus in the hippocampus. There is substantial neurogenesis throughout life in the human hippocampus as it is estimated that up to one third of human hippocampal neurons are subject to constant turnover.

Adult neurogenesis is linked to hippocampal-dependent learning and memory tasks and is reduced during aging. Recent evidence suggests that adult neurogenesis is altered in the neurodegenerative process of AD, but it is still controversial with some authors reporting increased neurogenesis, whereas others show reduced neurogenesis. In the human hippocampus, a sharp drop in adult neurogenesis has been observed in subjects with AD.”

One of the study’s limitations was its control group:

“There was a significant difference in age between controls [12, ages 50.7 ± 21.5] and AD patients [26, ages 81.2 ± 12.1], being the latter group older than the former group. Although we adjusted for age in the statistical differential methylation analysis, the accuracy of this correction may be limited as there is little overlap in the age ranges of both groups.”

https://clinicalepigeneticsjournal.biomedcentral.com/track/pdf/10.1186/s13148-019-0672-7 “DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis”

OCD and neural plasticity

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Update: this was retracted on February 23, 2021. The retraction note is at https://www.nature.com/articles/s41598-021-84474-5.

This 2019 New York rodent study investigated multiple avenues to uncover mechanisms of obsessive-compulsive disorder:

“Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum) may be causally linked. Numerous genetic and environmental factors may reduce striatum sensitivity and lead to maladaptive overcompensation, potentially accounting for a significant proportion of cases of pathological OCD-like behaviors.

Our results indicate that both the development and reversal of OCD-like behaviors involve neuroplasticity resulting in circuitry changes in BLA-DLS and possibly elsewhere.”

https://www.nature.com/articles/s41598-019-45325-6.pdf “Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism”

The researchers explored two genetic models of OCD, showed why these insufficiently explained observed phenomena, then followed up with epigenetic investigations. They demonstrated how and the degree to which histone modifications and DNA methylation regulated both the development and reversal of OCD symptoms.

However, the researchers also carelessly cited thirteen papers outside the specific areas of the study to support one statement in the lead paragraph:

“Novel studies propose that modulations in gene expression influenced by environmental factors, are connected to mental health disorders.”

Only one of the thirteen citations was more recent than 2011, and none of them were high-quality studies.

Transgenerational diseases caused by great-grandmother DDT exposure

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This 2019 rodent study from the labs of Dr. Michael Skinner at Washington State University found:

“The exposure of a gestating female during fetal gonadal sex determination to DDT can promote the epigenetic transgenerational inheritance of obesity and disease.

Transgenerational pathologies (F3 generation) of late puberty, obesity, testis, prostate, and multiple disease were observed in the DDT lineage males. Obesity, ovarian, kidney, and multiple disease transgenerational pathologies (F3 generation) were observed in the DDT lineage females.

Epigenetic biomarkers or diagnostics provide preliminary evidence for preconception diagnosis of increased susceptibility to transgenerational disease in offspring.”

For those of us who thought DDT was discontinued:

“DDT was banned in the USA in 1973, but it is still recommended by the World Health Organization for indoor residual spray. India is by far the largest consumer of DDT worldwide.

India has experienced a 5-fold increase of type II diabetes over the last three decades with a predisposition to obesity already present at birth in much of the population. Although a large number of factors may contribute to this increased incidence of obesity, the potential contribution of ancestral toxicant exposures in the induction of obesity susceptibility requires further investigation.”

Where are the human studies of this subject? Why aren’t follow-on generations’ diseases traced to the likely sources?

How many F3 great-grandchildren of women exposed to DDT during pregnancy are alive today? Millions, tens of millions?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536675 “Sperm epimutation biomarkers of obesity and pathologies following DDT induced epigenetic transgenerational inheritance of disease”

Infant DNA methylation and caregiving

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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)

What drives cellular aging?

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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, however:

“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?

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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).”

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

A. Although section 4’s heading was Biological Adaptiveness of Delusions, the reviewers never got around to discussing evolved roles of brain areas and beliefs (delusions). 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.”

B. 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.”

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

D. 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 / or more numerous beliefs (delusions) a person has, the less they feel meaning in life.

E. 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)?

F. 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 predecessor-successor diagrams for every step of a process. Not this one.

Regarding any 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.”

Another important transgenerational epigenetic inheritance study

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

“A cascade of epigenetic alterations initiated in PGCs [primordial germ cells of F3 males] appears to be required to alter epigenetic programming during spermatogenesis to modify the sperm epigenome involved in transgenerational epigenetic inheritance phenomenon.

Following fertilization there is a DNA methylation erasure to generate stem cells in the early embryo, which then remethylate in a cell type-specific manner. 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 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, agricultural fungicide vinclozolin was found to promote transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate developmental origins of 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. Fetal exposure initiates a developmental cascade (i.e., distinct developmental origins) of aberrant epigenetic programming, and does not simply induce a specific number of DMRs that are maintained throughout development.”

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 study’s main hypotheses were:

“Following fertilization, the hypothesis is that 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 apply them to human studies.

1. Don’t get off track by requiring that the same phenotype must be observed in each generation for there to be transgenerational epigenetic inheritance, because:

“Fetal exposure..does not simply induce a specific number of DMRs that are maintained throughout development.”

Animal transgenerational studies have shown that epigenetic inheritance mechanisms may both express different phenotypes for each generation, and entirely skip a phenotype in one or more generations!

2. Don’t limit your study designs to F1 children as did:

3. Don’t stop at F2 grandchildren as did:

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

The transgenerational impact of Roundup exposure

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This 2019 Washington 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 world 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 hypotheses of practices that test only effects on somatic cells, and don’t look for generational effects on germ cells?
  • Are tests 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

gettingwell4 0-1 star Wasted resources, Amygdala, Cerebellum, Epigenetics, Glutamate, Hippocampus, Limbic system, Lower brain, Memory, Neurochemicals, Serotonin, Stress , , , , , ,

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”