Maternal obesity causes heart disease in every offspring generation

This 2019 St. Louis rodent study found:

“We hypothesized that maternal obesity induces cardiac mitochondrial dysfunction in the offspring via transgenerational inheritance of abnormal oocyte mitochondria. All F1 to F3 descendants bred via the female in each generation were nonobese and demonstrated cardiac mitochondrial abnormalities.

Contrary to our hypothesis, male F1 also transmitted these effects to their offspring, ruling out maternal mitochondria as the primary mode of transmission. We conclude that transmission of obesity-induced effects in the oocyte nucleus rather than abnormal mitochondria underlie transgenerational inheritance of cardiac mitochondrial defects in descendants of obese females.”


For some reason, the researchers didn’t cite any of Dr. Michael Skinner’s research on epigenetic transgenerational inheritance. Their time, efforts, and resources would have been more productive had they used Dr. Skinner’s studies – such as the 2018 Epigenetic transgenerational inheritance of ovarian disease – as guides.

A podcast with the researchers is available here.

https://www.physiology.org/doi/abs/10.1152/ajpheart.00013.2019 “Maternal High-Fat, High-Sucrose Diet Induces Transgenerational Cardiac Mitochondrial Dysfunction Independent of Maternal Mitochondrial Inheritance” (not freely available)

Do genes or maternal environments shape fetal brains?

This 2019 Singapore human study used Diffusion Tensor Imaging on 5-to-17-day old infants to find:

“Our findings showed evidence for region-specific effects of genotype and GxE on individual differences in human fetal development of the hippocampus and amygdala. Gene x Environment models outcompeted models containing genotype or environment only, to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only.

Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene x Environment models for the majority of amygdaloid measures and minority of hippocampal measures. The fact that methylation models outcompeted gene x environment models in many instances is compatible with the idea that DNA methylation is a product of GxE.

A genome-wide association study of SNP [single nucleotide polymorphism] interactions with the prenatal environments (GxE) yielded genome wide significance for 13 gene x environment models. The majority (10) explained hippocampal measures in interaction with prenatal maternal mental health and SES [socioeconomic status]. The three genome-wide significant models predicting amygdaloid measures, explained right amygdala volume in interaction with maternal depression.

The transcription factor CUX1 was implicated in the genotypic variation interaction with prenatal maternal health to shape the amygdala. It was also a central node in the subnetworks formed by genes mapping to the CpGs in neonatal umbilical cord DNA methylation data associating with both amygdala and hippocampus structure and substructure.

Our results implicated the glucocorticoid receptor (NR3C1) in population variance of neonatal amygdala structure and microstructure.

Estrogen in the hippocampus affects learning, memory, neurogenesis, synapse density and plasticity. In the brain testosterone is commonly aromatized to estradiol and thus the estrogen receptor mediates not only the effects of estrogen, but also that of testosterone.”

https://onlinelibrary.wiley.com/doi/full/10.1111/gbb.12576 “Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome” (not freely available)

Because..Harvard?

This 2019 Harvard review entitled “Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms” DETRACTED from science. Readers would become less-informed on the subject due to poorly-researched statements such as:

“Non-Mendelian inheritance, termed transgenerational epigenetic inheritance,”

which wasn’t an adequate definition of the transgenerational epigenetic inheritance term.


Contributing to the paper’s misdirection was the omission of Dr. Michael Skinner from any of the 349 cited references. Hard to believe that ignoring his research wasn’t intentional, since a PubMed “transgenerational” search sorted by Best Match displayed Dr. Skinner as author or coauthor in 3 of the first 20 results:

The abstract asserted:

“How this epigenetic information escapes the typical epigenetic erasure that occurs upon fertilization and how it regulates behavior is still unclear.”

However, Another important transgenerational epigenetic inheritance study – published well before the current paper – was one of Dr. Skinner’s Washington State University lab studies that CLEARLY demonstrated contrary evidence.

Who benefits from hijacking a scientific term and ignoring groundbreaking research?

Why did the two editors approve for publication a paper with obvious omissions and egregious errors? Because..Harvard?

https://www.sciencedirect.com/science/article/abs/pii/S0959438818302204 “Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms” (not freely available)

Emotional responses and BDNF methylation

This 2019 German human study found:

“A critical role of BDNF [brain-derived neurotrophic factor] methylation in human amygdala response to negative emotional stimuli, whereby:

  • High BDNF methylation rates were for the first time shown to be associated with a high reactivity in the amygdala; and
  • High BDNF methylation and high amygdala reactivity were associated with low novelty seeking.

There was no interaction or main effect of the Val66Met polymorphism on amygdala reactivity.

Our data adds evidence to the hypothesis that epigenetic modifications of BDNF can result in an endophenotype associated with anxiety and mood disorders. However, since correlations do not prove causality:

  • A direct link between human BDNF mRNA/protein levels, methylation, amygdala reactivity and psychiatric disorders is still missing, demanding further research.
  • Determining the underlying directions of the relations between BDNF methylation, amygdala reactivity, and NS [novelty seeking] cannot be accomplished based on our data and must await further research.

The fact that our results mainly involve the right amygdala is in line with previous studies. Recent reviews suggest a general right hemisphere dominance for all kinds of emotions, and, more specifically, a critical role of the right amygdala in the early assessment of emotional stimuli.

The experimental fMRI paradigm utilized a face‐processing task (faces with anger or fear expressions), alternating with a sensorimotor control task. Harm avoidance, novelty seeking, and reward dependence were measured using the Tridimensional Personality Questionnaire.”

https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24825 “The role of BDNF methylation and Val 66 Met in amygdala reactivity during emotion processing”

Reversing epigenetic T cell exhaustion

This 2019 worldwide discussion among 18 experts concerned T cell exhaustion:

“‘T cell exhaustion’ is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumours.

Key questions remain about the potential to reverse the epigenetic programme of exhaustion and how this might affect the persistence of T cell populations.”


There were nearly a dozen viewpoints on “What do we mean by T cell exhaustion and/or dysfunction and how would you define this state?” 🙂

Answers to the question “What are the key controversies and outstanding research questions?” included:

  • “What are the cellular signalling and transcriptional pathways that drive the conversion to an exhausted T cell phenotype, and how can the chromatin and transcriptional changes of exhaustion be reversed in individual exhausted cells?
  • Whether and how we can manipulate signalling pathways to both activate and maintain T cell responses remain open questions, as does the question of whether pharmacological manipulations can reverse the epigenetic changes associated with exhaustion versus expand less-exhausted populations.
  • We need to define better the effects of the microenvironment on the induction of T cell exhaustion, the developmental trajectories of exhaustion and the point at which and extent to which exhaustion can be reversed. Understanding the consequences of unleashing T cells from exhaustion will also be crucial to designing the most effective therapeutic interventions.
  • When and how exhausted T cell populations are formed. The original view that they are terminally differentiated descendants of formerly ‘normal’ effector T cells has been challenged.
  • Whether the predysfunctional T cells themselves, or their more differentiated (and phenotypically dysfunctional) progeny, form the ultimate effector pool for control of human tumours.
  • How do the functions and states (subpopulations) of exhausted T cells change over time? Can the epigenetic state of exhaustion be reversed to form true effector or memory T cells, and is this required for improved cancer immunotherapy?
  • There is no definitive marker for exhausted T cells, although TOX may prove to be useful. Transcriptional profiles are informative, but epigenetic changes are more specific and robust. A major clinical question is whether exhausted T cells can be, or indeed need to be, reprogrammed to achieve therapeutic benefit.”

https://www.nature.com/articles/s41577-019-0221-9 “Defining ‘T cell exhaustion'” (not freely available)

Get outside today

This 2019 Finnish review focused on vitamin D’s immune system effects:

“The epigenome of human monocytes is at multiple levels sensitive to vitamin D. These data served as the basis for the chromatin model of vitamin D signaling, which mechanistically explains the activation of a few hundred primary vitamin D target genes.

Vitamin D and its receptor are able to antagonize the pro-inflammatory actions of the transcription factors nuclear factor activated T cells (NF-AT) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in T cells. In this way, vitamin D reduces autoimmunity, such as the onset and progression of multiple sclerosis, as well as chronic inflammation.

Population-wide recommendations do not take inter-individual variations into account, such as a different molecular response to vitamin D, which are expressed by the vitamin D response index. Instead of population-based recommendations for vitamin D3 supplementation there should be personalized recommendations in order to reach a vitamin D status that is optimized for an individual’s health protection.

Trained immunity implies that immune cells memorize challenges, to which they are exposed in their rather short lifespan, in form of changes of their epigenome leading to subtype specification. The stabilization of the epigenomes of the subtypes of monocytes, macrophages and dendritic cells by vitamin D can prevent or delay the onset of common age-related diseases.”


One of the five elements of the clinical trial Reversal of aging and immunosenescent trends was daily 3,000 IU vitamin D3 supplementation for nine months. That study’s monocyte findings included:

“Analysis of CyTOF‐defined immune cell populations revealed the most robust changes to be decreases in total and CD38‐positive monocytes and resulting increases in the lymphocyte‐to‐monocyte ratio (LMR). The changes in mean monocyte populations persisted 6 months after discontinuation of treatment, and the increase in LMR remained highly significant at 18 months as well.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753645/ “Vitamin D Signaling in the Context of Innate Immunity: Focus on Human Monocytes”

May you be the hero who solves your own problems

This 2019 Germany/US review subject was the failure of psychotherapy and pharmacotherapy:

“Each mental disorder raises its own host of issues. However, recent evidence across multiple meta-analyses on key mental disorders provides an overarching picture of limited benefits for both psychotherapy and pharmacotherapy.

Some differences for specific disorders are not strong enough to weaken the overall impression that a dead end has been reached in the treatment of mental disorders. For this reason, a paradigm shift seems to be required.”


Investigate the above linked Primal Therapy category to figure out what you could do for yourself. Follow the below review link for reasons to avoid treatments that waste your one precious life.

https://www.cambridge.org/core/journals/psychological-medicine/article/toward-a-paradigm-shift-in-treatment-and-research-of-mental-disorders/FDE68FF26E946276A334FA90ACE28D9F/core-reader “Toward a paradigm shift in treatment and research of mental disorders”