“..today we must assume that if our generation is suffering hardship, violence or the like, not only will we struggle to forget these difficult periods ourselves but our genes too will remember them, carrying traces to be passed on to the next generation or even several generations.”
From the 8 May 2015 post at Scilogs
The science behind a rapid paradigm shift
When the first human genome was decoded, popular thinking went: “If we know the genes, we know the person.” Today, barely 15 years later, science is in the middle of an exciting new area of research, which is entertaining interested members of the public with exciting, if not always serious, headlines. The field alleges that traumatic experiences can be passed down through the generations and even significantly affect the lives of grandchildren. As it turns out, the reality is that genes not only control, but are also controlled. And that is what epigenetics is all about – how are genes controlled and what factors can influence them?
Epigenetics refers to the meta-level of genetic regulation. Under the influence of external factors, epigenetic mechanisms regulate which genes are turned on and off. This helps our fixed genetic material to be more flexible. At the biochemical micro level, epigenetic regulators are responsible for how closely packed individual genomic regions are and therefore how accessible or not they are. This works by small adhered or detached chemical groups. The resulting marking of the genome is read by specialised enzymes that then cause the switching on or off of the genes.
As reasonable as this appears, one consequence is that we will have to say goodbye to a long-established dogma: the idea that genes are immutable in the creation of a living being. And, looking back through the history of science: was Lamarck right, after all? The 19th-century French biologist had claimed that organisms acquired traits to pass on to future generations . It is precisely this mechanism that epigeneticists are on the trail of today. Laboratory experiments with mice have demonstrated that a particular, targeted encoding of individual genes results in the changes being passed on to the offspring. Epigenetic changes, however, are so-called soft changes, as they can be undone. And that is medicine’s great hope – to be able to intervene in the control mechanism from the outside in order to be able to work against, for example, senile dementia.
At this point, the level of possible tension around this new field of research becomes clear. On the one hand, the idea that our human condition can be so strongly “manipulated” by environmental influences can be very disturbing. And rightly so. Previously, we may have had the upbeat expectation that although we are experiencing suffering, the next generation will have it better. However, today we must assume that if our generation is suffering hardship, violence or the like, not only will we struggle to forget these difficult periods ourselves but our genes too will remember them, carrying traces to be passed on to the next generation or even several generations.
A study often mentioned in this context is based on the analysis of data collected in the Netherlands over the years of hunger in 1944-45, during which the population there suffered particularly difficult conditions. The children born at this time were not only smaller, but, as adults, had an increased risk of obesity, cardiovascular problems and neuropsychiatric disorders. In turn, their offspring were again smaller than average – despite food being in ready supply and living conditions having greatly improved.
One way to address the growing heroin epidemic? Address lifestyle and environment components.
Certainly would be a public health way to stem folks dependence on substances that can often diminish quality of life and death.
From the 4 January 2014 Science Daily article (read the entire article at this link)
Researchers have discovered that sensitivity to pain could be altered by a person’s lifestyle and environment throughout their lifetime. The study is the first to find that pain sensitivity, previously thought to be relatively inflexible, can change as a result of genes being switched on or off by lifestyle and environmental factors — a process called epigenetics, which chemically alters the expression of genes.
From the 17 December 2013 ScienceDaily article
The fact that smoking means a considerable health risk is nowadays commonly accepted. New research findings from Uppsala University and Uppsala Clinical Research Center show that smoking alters several genes that can be associated with health problems for smokers, such as increased risk for cancer and diabetes.
We inherit our genes from our parents at birth. Later in life the genetic material can be changed by epigenetic modifications, i.e. chemical alterations of the DNA the affect the activity of the genes. Such alterations are normally caused by aging but can also result from environmental factors and lifestyle.
In a study recently published in the journal Human Molecular Genetics the researchers have examined how the genes are changed in smokers and users of non-smoke tobacco. They could identify a large number of genes that were altered in smokers but found no such effect of non-smoke tobacco.
t has been previously known that smokers have an increased risk of developing diabetes and many types of cancer, and have a reduced immune defence and lower sperm quality. The results from the study also showed that genes that increase the risk for cancer and diabetes, or are important for the immune response or sperm quality, are affected by smoking.
[News article] You Are What Your Father Eats: Father’s Diet Before Conception Plays Crucial Role in Offspring’s Health, Study Suggests
Mothers get all the attention. But a study led by McGill researcher Sarah Kimmins suggests that the father’s diet before conception may play an equally important role in the health of their offspring. It also raises concerns about the long-term effects of current Western diets and of food insecurity.
The research focused on vitamin B9, also called folate, which is found in a range of green leafy vegetables, cereals, fruit and meats. It is well known that in order to prevent miscarriages and birth defects mothers need to get adequate amounts of folate in their diet. But the way that a father’s diet can influence the health and development of their offspring has received almost no attention. Now research from the Kimmins group shows for the first time that the father’s folate levels may be just as important to the development and health of their offspring as are those of the mother. Indeed, the study suggests that fathers should pay as much attention to their lifestyle and diet before they set out to conceive a child as mothers do.
“We were very surprised to see that there was an almost 30 per cent increase in birth defects in the litters sired by fathers whose levels of folates were insufficient,” said Dr. Romain Lambrot, of McGill’s Dept. of Animal Science, one of the researchers who worked on the study. “We saw some pretty severe skeletal abnormalities that included both cranio-facial and spinal deformities.”
The research from the Kimmins’ group shows that there are regions of the sperm epigenome that are sensitive to life experience and particularly to diet. And that this information is in turn transferred to a so-called epigenomic map that influences development and may also influence metabolism and disease in the offspring in the long-term. (The epigenome is like a switch, which is affected by environmental cues, and is involved in many diseases including cancer and diabetes. The epigenome influences the way that genes are turned on or off, and hence how heritable information gets passed along).
Although it has been known for some time that there is a massive erasure and re-establishment that takes place in the epigenome as the sperm develops, this study now shows that along with the developmental map, the sperm also carries a memory of the father’s environment and possibly even of his diet and lifestyle choices.
“Our research suggests that fathers need to think about what they put in their mouths, what they smoke and what they drink and remember they are caretakers of generations to come,” said Kimmins. “If all goes as we hope, our next step will be to work with collaborators at a fertility clinic so that we can start assessing the links in men between diet, being overweight and how this information relates to the health of their children.”
- Dad’s diet may influence long-term health of offspring (foxnews.com)
- Your dad’s diet before your conception may have affected your health: McGill study (montreal.ctvnews.ca)
- Fathers Should Watch What They Eat Before Conceiving: Bad Diet Impacts Sperm, Has Long-Term Effect On Offspring (medicaldaily.com)
- You are what your father eats (eurekalert.org)
The day after I published this, I answered a related question about busyness at Quora.
Resources that were included in the answer are listed below.
With some 300 million people around the world living with asthma, a study by Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) researchers that was released ahead-of- print found for the first time that maternal smoking can cause the third generation of offspring to suffer from the chronic lung disease.
The study, published online by theAmerican Journal of Physiology — Lung Cellular and Molecular Physiology, reported that maternal nicotine exposure during pregnancy is linked to asthma in the third generation in disease models. This is known as a “transgenerational” linkage because the third generation was never directly exposed to nicotine or smoking. Previous research had found nicotine exposure was linked to asthma in the second generation, or was a “multigenerational” cause of asthma.
“Even though there are multiple causes for childhood asthma, research linking this serious chronic condition to maternal nicotine exposure during pregnancy for up to three generations should give mothers-to-be even more reasons to reconsider smoking,” said Virender K. Rehan, MD, an LA BioMed lead researcher and the corresponding author of the study. “Eliminating the use of tobacco during pregnancy could help halt the rise in childhood asthma and ensure healthier children for generations to come.”
The current study “paves the way for determining the epigenetic mechanisms” behind smoking and the transmission of asthma to future generations, the researchers concluded.
Want to learn more about epigenetic? Here’s some good Web sites
- Learn Epigenetics (University of Utah)
HowStuffWorks “How Epigenetics Works” (How stuff works)
- Epigenetics (National Institutes of Health)
Related Psychiatric/Psychologic/Counseling Resources (via MedlinePlus)
- Mental Health Providers: Tips on Finding One(Mayo Foundation for Medical Education and Research)
- Psychotherapies(National Institute of Mental Health)
- Therapy and Counseling(American Academy of Family Physicians)
From the 27 August 2013 Director’s blog item (National Institutes of Health)
Once in a while a research publication reveals an entirely new perspective on a fundamental issue in biology or medicine. Today’s blog is about such a paper. The story, though complex, is very significant.
The choreography of human brain development is amazing, but quite mysterious. Today’s post highlights a study  that reveals the locations of some of the chemical choreographers that collaborate with DNA to orchestrate these fancy moves in the brain.
This complex developmental dance starts in the womb as our brain cells arise, migrate to their proper locations, and mature. By the time we’re born, each of us has close to 100 billion of these cells, called neurons. But that’s not all. The brain also contains lots of other cell types—especially glia. Glial cells were previously thought to act primarily as servants to the neurons, but they’re actually more like partners. Our birth inventory is just the first act. Over the course of our lives, our experiences and environment continue to shape and re-shape the brain’s connections, albeit in varying paces and patterns.
The millions of chemical tags that modify or mark the genome tell it what to do, and when and where to do it. Taken together, we call this diverse collection of chemical cues the “epigenome.”
Just as genetic mutations can lead to disease, glitches in DNA methylation may also trigger or increase the severity of brain disorders. Several studies have already linked abnormal methylation with disorders like schizophrenia, and conditions like Traumatic Brain Injury. This research is particularly exciting because these DNA methylation tags are not permanent. So, if we discover patterns of methylation that cause particular brain diseases, we can develop strategies to restore the healthy epigenetic profile—in effect, to bring those errant brain cells back in step with the dance of normal brain development.
Caption: Researchers mapped methylation sites in genomes of neurons and glia in the frontal cortex. mCH methyl tags, or non-CG methylation (purple stars), were absent at birth, but were added rapidly during the first few years of life and then more slowly until about age 30. After age 50, the number of mCH tags declined.
Credit: Eran Mukamel, Salk Institute
This study is a powerful example of how recent technological advances are revealing the secrets and complexities of the human brain—a process we hope to accelerate with the start of the BRAIN initiative!
 Global epigenomic reconfiguration during mammalian brain development. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR. Science. 2013 Aug 9;341(6146):1237905.
 Sequence data can be downloaded from National Center for Biotechnology Information GEO (GSE47966). The analyzed data is also available for browsing.
- Brain DNA Methylation Increases Approaching Adulthood (futurepundit.com)
- Epigenomic Maps Show How Brain Circuits Change From Birth To Adulthood (healthbeauty4426.wordpress.com)
- Modern Parenting Style May Hinder Brain Development (thecollegefix.com)
- Brain Epigenome Found To Change Dramatically From Infancy to Adolescence (33rdsquare.com)
- Scientists find key signal that guides brain development (medicalxpress.com)
- A new way of thinking about how the brain works | Mo Costandi (theguardian.com)
- New mode of cellular communication discovered in the brain (psypost.org)
- Failure to destroy toxic protein — not buildup of protein itself — contributes to Huntington’s disease (sciencedaily.com)
- Don’t Let the Trash Pile Up For A Healthy Brain (medindia.net)
A University of British Columbia and Centre for Molecular Medicine and Therapeutics (CMMT) study has revealed that childhood poverty, stress as an adult, and demographics such as age, sex and ethnicity, all leave an imprint on a person’s genes. And, that this imprint could play a role in our immune response. …
Known as epigenetics, or the study of changes in gene expression, this research examined a process called DNA methylation where a chemical molecule is added to DNA and acts like a dimmer on a light bulb switch, turning genes on or off or setting them somewhere in between. Research has shown that a person’s life experiences play a role in shaping DNA methylation patterns. ..
“We found biological residue of early life poverty,” said Michael Kobor, an associate professor of medical genetics at UBC, whose CMMT lab at the Child & Family Research Institute (CFRI) led the research. “This was based on clear evidence that environmental influences correlate with epigenetic patterns.” ..
- Genes, Immune System Shaped by Childhood Poverty, Stress (dogmaandgeopolitics.wordpress.com)
- Kobor, CMMT study shows genes and immune system shaped by childhood poverty, stress (aplaceofmind.ubc.ca)
- New Study: Stress Increases Risk of Mental, Physical Illness (baktoedenherbalproducts.wordpress.com)
From the 2 March 2012 article at Science News Daily
Washington State University researcher has demonstrated that a variety of environmental toxicants can have negative effects on not just an exposed animal but the next three generations of its offspring.
The animal’s DNA sequence remains unchanged, but the compounds change the way genes turn on and off — the epigenetic effect studied at length by WSU molecular biologist Michael Skinner and expanded on in the current issue of the online journalPLoS ONE.
While Skinner’s earlier research has shown similar effects from a pesticide and fungicide, this is the first to show a greater variety of toxicants — including jet fuel, dioxin, plastics and the pesticides DEET and permethrin — promoting epigenetic disease across generations…
The field opens new ground in the study of how diseases develop. While toxicologists generally focus on animals exposed to a compound, Skinner’s work further demonstrates that diseases can also stem from older, ancestral exposures that are then mediated through epigenetic changes in sperm.
The study was funded by the U.S. Army to study pollutants that troops might be exposed to. Skinner and his colleagues exposed pregnant female rats to relatively high but non-lethal amounts of the compounds and tracked changes in three generations of offspring.
The researchers saw females reaching puberty earlier, increased rates in the decay and death of sperm cells and lower numbers of ovarian follicles that later become eggs. Future studies can use the molecular tools for risk assessment analysis
- Effects of environmental toxicants reach down through generations (eurekalert.org)
- Epigenetics research continues: Variety of toxicants can harm subsequent generations (wsunews.wsu.edu)
- You Might Be Infertile Because Your Grandparents Were Mucking Around in Harmful Chemicals [Science] (gizmodo.com)
- Pollutants long gone, but disease carries on (sciencenews.org)
- Epigenetics and Drug Addiction (epigenomics.wordpress.com)
- Epigenetics: A Turning Point in our Understanding of Heredity (blogs.scientificamerican.com)
- Linking everyday chemicals to disease: New science keeps on intensifying the writing on the wall (blogs.edf.org)
- EPA Supports Environmental Justice for New Jersey Farm Workers (treehugger.com)
- The US Environmental Remediation Services Industry to Reach US$8.29 Billion by 2015, According to New Report by Global Industry Analysts, Inc. (prweb.com)
- Mobile App Helps Public Keep an Eye on Toxic Neighbors (prweb.com)
A University of Cambridge study, which set out to investigate DNA methylation in the human heart and the ‘missing link’ between our lifestyle and our health, has now mapped the link in detail across the entire human genome.
The new data collected greatly benefits a field that is still in its scientific infancy and is a significant leap ahead of where the researchers were, even 18 months ago.
Researcher Roger Foo explains: “By going wider and scanning the genome in greater detail this time – we now have a clear picture of the ‘fingerprint’ of the missing link, where and how epigenetics in heart failuremay be changed and the parts of the genome where diet or environment or other external factors may affect outcomes.” …
DNA methylation leaves indicators, or “marks”, on the genome and there is evidence that these “marks” are strongly influenced by external factors such as the environment and diet. The researchers have found that this process is different in diseased and normal hearts. Linking all these things together suggest this may be the “missing link” between environmental factors and heart failure.
The findings deepen our understanding of the genetic changes that can lead to heart diseaseand how these can be influenced by our diet and our environment. The findings can potentially open new ways of identifying, managing and treating heart disease.
The DNA that makes up our genes is made up of four “bases” or nucleotides – cytosine, guanine, adenine and thymie, often abbreviated to C, G, A and T. DNA methylation is the addition of a methyl group (CH3) to cytosine.
When added to cytosine, the methyl group looks different and is recognised differently by proteins, altering how the gene is expressed i.e. turned on or off.
DNA methylation is a crucial part of normal development, allowing different cells to become different tissues despite having the same genes. As well as happening during development, DNA methylation continues throughout our lives in a response to environmental and dietary changes which can lead to disease.
As a result of the study, Foo likens DNA methylation to a fifth nucleotide: “We often think of DNA as being composed of four nucleotides. Now, we are beginning to think there is a fifth – the methylated C.”
Foo also alludes to what the future holds for the study: “…and more recent basic studies now show us that our genome has even got 6th, 7th and 8th nucleotides… in the form of further modifications of cytosines. These are hydroxy-methyl-Cytosine, formylCytosine and carboxylCytosine = hmC, fC and caC! These make up an amazing shift in the paradigm…”
As in most studies, as one question is resolved, another series of mysteries form in its place. The study shows that we are still on the frontier of Epigenetics and only just beginning to understand the link between the life we lead and the body we have.
- Environment and diet leave their prints on the heart (eurekalert.org)
- Diet, environment leave their prints on the heart (scienceblog.com)
- Controlling patterns of DNA methylation (medicalxpress.com)
- Epigenetic changes often don’t last, probably have limited effects on long-term evolution, research finds (sciencedaily.com)
- Epigenetics again: will it cause a revolution in evolution? (whyevolutionistrue.wordpress.com)
- Your Living Conditions as a Child May Be Detectable In Your DNA for Life By Clay Dillow (imullins89.wordpress.com)
- Welcome to the Genome Engineering Wordle (genome-engineering.com)
- Genome Engineering guest blog on BioNews: Europe leads the way in epigenome mapping (genome-engineering.com)
- Genome engineering – Method 3: Correction (genome-engineering.com)
- Carnival of Evolution #39 (genome-engineering.com)