A Mechanism Behind the Yo-Yo Effect

 

The yo-yo effect in dieting is something that has been observed for a long time- someone tries to lose weight but gains it all back right after the diet. Recently, scientists have discovered a mechanism behind the yo-yo effect that could help explain why it occurs. By analyzing fat cells from overweight mice and of mice that lost weight through dieting, it was revealed that obesity leads to characteristic epigenetic changes in the nuclei of the fat cells. These changes were found to have remained even after the loss of weight, where the cells remember the overweight state and find it easier to return to it. The mice with those epigenetic markers were able to gain the weight back faster when they resumed a high fat diet. A similar study was carried out on humans and the results were found to be consistent with the mice study.

In my opinion, this is a study that has produced useful information. By discovering a mechanism for why the yo-yo effect occurs on the molecular level, we can better understand how and why it occurs in humans. We could perform more research on this topic in order to potentially develop strategies to prevent it from happening to people who are trying to lose weight and keep it off. This study could have many benefits for many of these people.

Using an 'Epigenetic Clock' to Predict How Long One May Live

    The article, Could a Cheek Swab Predict When You Might Die, jumps right into a new test called a CheekAge and how this test can, someday, accurately predict how long someone has to live, as well as analyze mortality rates for an individual. CheekAge test tracks epigenetics via simply swabbing cells within the mouth.  Epigenetics tracks how a person's environment or lifestyle can alter how genes function throughout their lifespan. Typically, when researchers observe epigenetics, they follow a key tracker: DNA methylation. DNA methylation is a phenomenon where, without changing the essential composition of the gene, but the gene's ability to function/ gene activity is a result of molecular alteration or shifts in the DNA segments. The CheekAge takes advantage of DNA methylation by analyzing specific DNA methylation patterns from cells inside the mouth collected via a swab. CheekAge almost acts as an "epigenetic clock,"  subsequently examining and comparing results from the test to basic methylation patterns associated with life span "mile markers." 

    Dr. Maxim Shokhirev and his team of colleagues conducted a study that involved participants who underwent testing once every three years for DNA methylation via blood cell analysis-- roughly 450,000 different methylation sites on each of their genomes were taken and observed. These same participants underwent the CheekAge test, and the results were examined and compared. Dr. Shokhirev and colleagues concluded that CheekAge is accurately and significantly associated with mortality, this was concluded through extensive and longstanding datasets. Dr. Shokhirev and his team observed specific methylation sites that seemed pivotal in determining when one might die. One gene site possibly linked to suppressing cancer is PDZRN4 and ALPK2, a gene linked to heart health and cancer development. Other methylation sites have been connected to other health diseases and syndromes, such as inflammation, metabolic syndromes, and even osteoporosis. These genes can be analyzed to see if they significantly impact the lifespan of an individual. 

    Currently, blood-based epigenetic testing is the preferred method. However, the CheekAge could be a cheaper, faster, more convenient, and a valuable alternative to analysis of tracking the biology of aging, as it uses a simple, noninvasive cheek swab rather than a blood sample being drawn from a patient. 

I found this article interesting because the idea of using a cheek swab to date and potentially predict mortality is foreign yet so interesting, which is why it sparked my curiosity. Regardless, future studies still need to be conducted to identify and clarify other health-related relations that can be linked to CheekAge. However, I believe CheekAge can be used as a means of reducing some healthcare costs [a very prevalent and pervasive crisis in this day and age] since CheekAge is a simpler, cheaper, and faster method of epigenetic testing, making healthcare more widely accessible and available to people. Potentially, being able to use CheekAge to determine the frequency of age-related diseases, duration of health spans, and better predict risk rates for individuals diagnosed with life-threatening diseases could remarkably change the healthcare system for the better!

A Promising Development of a Gene-Silencing Tool

Sonia Vallabh, MIT and Havard Senior Group Leader, and her team were researching a type of prion disease known as fatal familial insomnia. Vallabh began her research on this prion disease after finding out she carries the disease-causing genes and that there are no current treatments, preventatives, or therapies for the fatal disease. Knowing that she would develop fatal familial insomnia in the years to come, Vallabh knew that she was racing time to develop her own treatment.

Less than two years after starting, Vallabh, Weissman, and other contributors developed gene-silencing tools that are now referred to as, "CHARMs", that can turn off the specific necessary genes to prevent prion disease proteins from being created. The CHARMs can turn off these specific genes via epigenetic editing where chemical tags are added to DNA to silence specific gene sequences. The benefits of CHARM are that the genes are kept intact so no DNA is destroyed and epigenetic editing will keep the genes suppressed with only one treatment instead of needing to constantly take pills.

The team is now working on taking these "molecular tools" and making them more versatile in their ability to provide therapy and fight against other neurodegenerative diseases. Although human trials have not taken place yet, the concept and technology have been developed and are revolutionary to the battle against neurodegenerative diseases. It is very likely that soon human trials will begin using CHARMs as a therapy and preventative measure against prion diseases. The speed at which this technology has been developed is impressive; however, passing human trials has still yet to come, which could display potential side effects that could render CHARMs ineffective.

https://news.mit.edu/2024/charmed-collaboration-creates-therapy-candidate-fatal-prion-diseases-0627

https://rarediseases.info.nih.gov/diseases/6429/fatal-familial-insomnia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003136/

Research Finds Shared DNA Signature of Identical Twins

Identical siblings are used to sharing a lot with their twin, including their DNA. But new research suggests that they also share a distinct marker of their twin status, not encoded within their DNA, but rather on it. This marker is found within the epigenome, consisting of chemical tags along the DNA that regulate gene activity without changing the genetic sequence. Researchers discovered that identical twins universally exhibit a common set of these markers, which remains consistent from birth through adulthood. 

The shared epigenetic markers can help identify individuals who were conceived as identical twins but lost their sibling in the womb or were separated at birth. This research lays the groundwork for understanding the process of monozygotic twinning, which remains a mystery despite its long-standing fascination. Identical twins form when a fertilized egg splits into two embryos, a process with unknown triggers. Jenny van Dongen, an epigeneticist at Vrije Universiteit Amsterdam, says the biological process that generates twins “is an enigma.”

During early development, both twins and non-twins undergo numerous epigenetic changes that activate or deactivate genes as the embryo forms. Some of these changes might explain minor distinctions between identical twins. So to better understand what makes a zygote split to form identical twins, “it makes sense to look at epigenetics,” van Dongen says.

By analyzing over 450,000 genomic sites in nearly 6,000 monozygotic and dizygotic twins, they compared identical twins with fraternal ones, eliminating influences from shared womb experiences. They identified 834 spots where identical twins exhibited remarkable similarity in epigenetic marks, particularly in centromere and telomere regions and near genes governing early developmental processes, like cell adhesion regulation. The health implications of these differences remain uncertain. These shared epigenetic patterns were consistent across twins of various ages and geographical locations- and even in different cell types. The researchers developed a test with an 80 percent accuracy rate to identify identical twins, including those affected by vanishing twin syndrome or separated at birth.

“This is a very, very important finding that opens up a lot of avenues of inquiry,” says Segal, the developmental psychologist. For example, identical twins are predisposed for a variety of conditions, from left-handedness to certain congenital disorders such as spina bifida, where the spine fails to develop properly. Perhaps, for some portion of people, these conditions stem from being an unknown identical twin, she says. 

Genetic research, and quite frankly all research, regarding twins always seems so interesting! It's quite cool how twins have piqued interest across cultures and traditions throughout history- and it’s even cooler to see how science develops deeper into understanding twins and the biological mechanisms behind it. 

Sources: 

https://www.nature.com/articles/s41467-021-25583-7

https://www.sciencenews.org/article/identical-twin-siblings-common-set-chemical-markers-dna-epigenetics

Cell Division: A Proposed Model for Cell Identity Preservation

While all cells in the human body contain the same DNA (genetic instructions), each cell expresses only the genes needed to become the cell type it is (i.e. neuron, lymphocyte, cardiomyocytes). Each cell’s fate is largely determined by chemical modifications to the histone proteins around the DNA, which control gene expression. Considering that these cells lose half of their modifications when replicating in cell division, a new MIT study suggests that these cells maintain their memory of what cell type they’re supposed to be through the 3D folding pattern of its genome determining which portions will be marked by chemical modifications. Essentially, the way that these chromosomes were folded are like a blueprint to determine where the remaining marks should go. Thus, by juggling between 3D folding and the marks, the epigenetic memory can be preserved over hundreds of divisions.

In general, this proposed model provides valuable insight into how epigenetic markings play a role in establishing cell identity and maintaining this memory after cell division. Through this model, biologists may be able to better understand how this epigenetic memory of cell identity is lost as cells begin to age and potentially better understand the epigenetic mechanisms underlying our genome.

For more information, view the news article linked here and the journal publication of the research study linked here.

Decoding The Complexity of Alheizmer’s Disease

                                     Decoding The Complexity of Alheizmer’s Disease

Alheizmer’s disease has been one that has torn people and families apart because of its horrible side effects. Many people who are diagnosed with Alheizmer’s struggle to live a normal life and most of the time need someone to aid them all hours of the day. This disease affects over six million people in the U.S. and there is very little treatment for slowing down the disease.

Scientists are attempting to find new targets for Alheizmer’s and different ways to effectively treat it. They have started working with different analyses on genomic, epigenomic, and transcriptomic changes that occur in the cell type in the brains of the patients with Alheizmer’s. The researchers examined how gene expression is altered as Alzheimer's disease advances using over 2 million cells from over 400 postmortem brain tissues. Additionally, they monitored alterations in the epigenetic modifications of cells, which aid in identifying the genes that are active or inactive in a certain cell. When combined, these methods provide the most comprehensive understanding of the genetic and molecular causes of Alzheimer's disease to date. 

In my opinion, this is a great study that is being conducted. There are many people who struggle with this disease every year for there to not be a stronger way to treat the disease. Through genetics it can provide a major breakthrough and help even possibly reverse the disease slightly. It is evident that the treatments we have today are not cutting it and it is not doing a strong enough job to help patients recover. This study is a very promising one as it contributes to fighting a disease that is devastating around the entire country.

Links:

https://news.mit.edu/2023/decoding-complexity-alzheimers-disease-0928

https://journals.physiology.org/doi/full/10.1152/physrev.00015.2020

Possible Link of Epigenetic Changes to Cannabis Use

 

Cannabis is known to be linked to health problems, but in a recent study could give more insight to the epigenetics. In humans methylation of the DNA occurs, where methyl groups are attached to the DNA. This results in a change in gene expression without changing the genetic makeup. The use of cannabis has been known to contribute to the aging process by methylation. A study was conducted to determine if there was a linkage between specific epigenetic factors with the use of cannabis. The 1000 participants of the study notified their use over time and provided blood samples. The blood samples were taken after 15 years of using cannabis and after 20 years. The study observed the blood samples that were five years apart and see the DNA methylation levels. The study doesn't prove that cannabis is the direct cause of health issues but it could associate cannabis as a contributor to cell proliferation, infection and psychiatric disorders. Although the research has brought more insight into the long-term effects of cannabis use.

Researching the epigenetics of cannabis could help prevent severe health issues. This study could be continued and be used to observe the methylation of the DNA. If there are consistent patterns where the methyl group is attached, then that information can be used to help mitigate the health problems. The study could also be used to see if there are certain groups that are more at risk for the epigenetic changes due to cannabis. 

Sources:

Science Alert

SciTechDaily

Does Exercise Alter how Gene's Behave?

 Identical twins can often develop differing diseases throughout their lifetime according to a new study. One of the main determinants of this is how physically active each twin is during their lifetime. An exercise study was done on 70 sets of twins over the course of seven years. Activity trackers were given to each participant to track their activity levels. It found that the twin with higher physical activity levels  showed lower signs of metabolic disease. Since twins have nearly identical genes, this would indicate that there were likely epigenetic changes for the more active twin. Epigenetics is the study of how your environment and your behaviors can change the way your genes function. The epigenetic markers for the more active twin showed that they were linked to having a lower metabolic syndrome, which is a condition that can lead to having type 2 diabetes, heart disease, etc. There were also epigenetic changes noted for the more physically active twins BMI and waist size.  Thus proving that we do have some say in the diseases and health problems people often face in old age. Something as simple as taking a 30 minute walk everyday could have life altering effects down the road. Hopefully this study will encourage people to stay more physically active and to also realize their daily behaviors have a huge say in their health.

A Discovery in the Field of Epigenetics

 Our DNA is the blueprint to "building" our bodies and adjustments to the blueprint can be made by epigenetic marks. These marks are DNA modifications that do not change the underlying genetic code but include extra information on top of it, which can eventually be inherited. Epigenetic marks regulate gene expression and suppress transposons (also known as "jumping genes") that can threaten the integrity of one's genome.  Dr. Irina Arkhipova, senior scientists in the Marine Biological Laboratory's Josephine Bay Paul Center, shares a bacteria named bdelloid rotifers, found in small freshwater animals, has been discovered to contain a novel epigenetic mark. This was measured to have happened about sixty million years ago. "This discovery marks the first time that a horizontally transferred gene has been shown to reshape the gene regulatory system in a eukaryote" says Kenney, author of the article. According to Dr. Arkhipova, horizontally transferred genes are known to preferentially be operational genes and not regulatory. In my opinion, this event is fascinating- how a single, horizontally transferred gene can form a whole new regulatory system, when the existing regulatory systems are already complicated. A piece of bacterial DNA and eukaryotic DNA become joined in the bdelloid rotifers' genome and they form a functional enzyme. 

Epigenetic treatments: New allies for chemotherapies?

 

The epigenetic changes acquired by tumor cells during chemotherapy treatment were examined cell by cell by a research team directed by Celine Vallot, CNRS Research Director in the Laboratoire Dynamique de l'information Génétique: Bases Fondamentales et Cancer (CNRS/Institut Curie/Sorbonne Université). The scientists found the genes whose expression allowed cells to endure treatment, as well as the epigenomic alterations that govern them, in collaboration with Léila Périé's team at the Physico-chimie Curie (CNRS/Institut Curie/Sorbonne Université). Scientists discovered that in the absence of treatment, epigenomic markers lock the expression of certain genes, and that this lock is broken by chemotherapy in rare cells. All cancer cells remain responsive to treatment if this lock is kept from jumping. Scientists demonstrated this by employing epi-drugs, which are pharmacological substances that prevent epigenetic marks from being removed, on animal models of breast cancer. These compounds must yet be modified for human usage.

These findings show that the epigenome has a role in cancer treatment resistance. Scientists are currently working hard to figure out how to apply this principle to humans in a therapeutic way. Scientists believe that if future clinical trials are successful, these epi-treatments could be used in concert with chemotherapies to extend their effectiveness in patients.

Personally, if this treatment does become successful, this would open up of a lot opportunities, as well as give hope to a lot patients that are going through chemotherapy, or any other cancer treatment. This study will also help better understand cancer cells, and also might lead to a step forward into finding a cure to cancer in a foreseeable future.

Links to articles:

https://www.sciencedaily.com/releases/2022/04/220411113725.htm

https://newsexplorer.net/epigenetic-treatments-new-allies-for-chemotherapies-s1138753.html

Possible Correlation Between Maternal Depression and Gene Expression in Fetuses

        In an article from The Scientist, Chloe Tenn discusses how depression may be correlated with epigenetic changes to the placenta in pregnant women. The connection of maternal depression and stress to the developing fetus has not yet been proven, but is currently under investigation. The National Institutes of Health (NIH) monitored over 300 women during their pregnancies between 2009 and 2013. They used surveys to assess their mental health at six intervals during their pregnancies and compared them to placental tissue samples they collected after delivery. 

     After comparing the data NIH genetic epidemiologists discovered that in their sample of women maternal depression was linked with 16 methylation sites, while stress was linked to another two sites. DNA methylation regulates gene expression, and typically acts to repress gene transcription. Two of the sites that were found to be linked with depression are associated with changes in the expression of ADAM23 and CTDP1 genes. These genes affect neurodevelopment and psychiatric conditions such as schizophrenia and bipolar disorder.
       

    Opinion: The sample size of the experiment was quite small, but the reasoning seems sound. Much more research will be needed to come to a conclusion, but depression and stress have an impact on hormones which could lead to epigenetic consequences for children still in utero. 

Can Genetics Explain Human Behavior?

Link to article: can-genetics-explain-human-behavior--66318
Supporting article: PMC2944040

In this article, the author talk about how humans have "met their maker" by discovering their DNA structure and genome. Basically, it was discovered that our DNA has the ability to determine many of our behaviors such as procrastination, extraversion, adultery, alcoholism, liberalism and more. However there's more to it that the genome itself, also known as epigenetics. It is all tied to "genes encoding transcription factors that regulate gene expression" which is dependent on the environment of an individual. A person's environment alters the chemicals that influence gene expression. "More recent studies show that mRNA can also be modified in ways that affect protein synthesis, a process called epitranscriptomics that adds yet another layer of complexity to the prediction of phenotypes from genotypes." Through research it was found that maternal care and child abuse alters the hypothalamic-pituitary-adrenal and the ability of individuals ability to handle stress, making them more suicidal and/or more likely to suffer from mental disorders. Upon examining the neuron-specific glucocorticoid receptor (NR3C1) promoter of suicide victims with childhood abuse and those without, it was found that there is a decrease in glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. 



I found this article very interesting as it shows the affect of an individual's environment on their behaviors. This proves that we can get rid of undesirable traits and create a mentally healthy, none abusive,  productive individuals that demonstrate high ethics if they were granted a stable environment where they can live up to their potential.