Consuming alcohol leads to epigenetic changes in brain memory centers -- ScienceDailyn, in mouse models, how acetate -- a byproduct of the alcohol breakdown produced mostly in the liver -- travels to the brain's learning system and directly alters proteins that regulate DNA function. This impacts how some genes are expressed and ultimately affects how mice behave when given environmental cues to consume alcohol. Their findings were published today in Nature. "It was a huge surprise to us that metabolized alcohol is directly used by the body to add chemicals called acetyl groups to the proteins that package DNA, called histones," said the study's senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the departments Cell and Developmental Biology and Biology, and director of the Penn Epigenetics Institute. "To our knowledge, this data provides the first empirical evidence indicating that a portion of acetate derived from alcohol metabolism directly influences epigenetic regulation in the brain."
Dads' Nicotine Use May Cause Cognitive Problems for Children and Grandchildren - Neuroscience NewsAnalysis of spermatozoa from the original nicotine-exposed males indicated that promoter regions of multiple genes had been epigenetically modified, including the dopamine D2 gene, critical for brain development and learning, suggesting that these modifications likely contributed to the cognitive deficits in the descendants.
How a single binge drinking episode affects gene that regulates sleep: Discovery explains alcohol's link to brain activity, sleep disturbances -- ScienceDailyUsing a mouse model, Thakkar monitored the effect of binge drinking on sleep patterns. Thakkar found mice exposed to binge drinking experienced a significant increase in non-rapid eye movement sleep four hours post-binge, followed by increased wakefulness and reduced sleep during subsequent sleep periods. Thakkar also discovered post-binge mice did not experience an increase in a sleep promoting chemical, adenosine, in the brain nor increased sleep pressure during sleep deprivation. The research also revealed binge alcohol consumption affects the gene that regulates sleep, resulting in sleep disturbances. "What we have shown in this research is that a particular gene -- which is very important for sleep homeostasis -- is altered by just one session of binge drinking," Thakkar said. "We were not expecting this. We thought it would be affected after multiple sessions of binge drinking, not one. That tells you that as soon as you consume four drinks, it can alter your genes."
Does physical activity influence the health of future offspring? Study finds an intergenerational benefit -- ScienceDailyWhen Fischer and co-workers exposed mice to a stimulating environment in which they had plenty of exercise, their offspring also benefited: compared to the mice of a control group, they achieved better results in tests that evaluate learning ability.
Three genes essential for cells to tell time -- ScienceDaily"Many researchers in this field have long suspected oxidative stress and circadian rhythms are somehow connected because of the cycles of photosynthesis and DNA replication we see even in ancient organisms; photosynthesis requires sunlight and creates free radicals that could damage DNA, so cells postpone DNA replication and cell division until nighttime when photosynthesis has stopped. We are very excited about our results because we can approach the origin of the circadian clock by connecting oxidative stress and circadian regulation through the Ask genes," said Fukada.
Timing is everything, to our genes -- ScienceDailyUsing RNA sequencing, the research team tracked gene expression in dozens of different non-human primate tissues every 2 hours for 24 hours. The team found that each tissue contained genes that were expressed at different levels based on the time of day. However, the number of these "rhythmic" genes varied by tissue type, from around 200 in pineal, mesenteric lymph nodes, bone marrow and other tissues to more than 3,000 in prefrontal cortex, thyroid, gluteal muscle and others. In addition, genes that were expressed most often tended to show more rhythmicity, or variability by time. Of the 25,000 genes in the primate genome, nearly 11,000 were expressed in all tissues. Of those (which mostly govern routine cellular functions, such as DNA repair and energy metabolism), 96.6 percent were particularly rhythmic in at least one tissue, varying drastically by when they were sampled.
Clock protein controls daily cycle of gene expression by regulating chromosome loops: New understanding of Rev-erb's role has implications for metabolic disorders, cardiovascular disease, and cancer -- ScienceDailyHuman physiology works on a 24-hour cycle of gene expression (when the chromosome coding region is translated by RNA and then transcribed to make protein) and is controlled by the body's molecular clock. Core clock proteins activate or repress protein complexes that physically loop one part of a chromosome to become adjacent to a distant part of the same chromosome. The Penn team showed that daily oscillations of Rev-erb control gene expression in the mouse liver via interactions between on-and-off regions on the same chromosome. Previous work from the team demonstrated that by 5 p.m., Rev-erb increases to its highest concentration in mouse liver, where it turns off certain genes and therefore protein transcription. But as the day turns to night, its concentration steadily decreases and nearly vanishes from the liver by 5 a.m.
The Best Thing to Eat Before a Workout? Maybe Nothing at All - The New York TimesMost obviously, the men displayed lower blood sugar levels at the start of their workouts when they had skipped breakfast than when they had eaten. As a result, they burned more fat during walks on an empty stomach than when they had eaten first. On the other hand, they burned slightly more calories, on average, during the workout after breakfast than after fasting. But it was the impacts deep within the fat cells that may have been the most consequential, the researchers found. Multiple genes behaved differently, depending on whether someone had eaten or not before walking. Many of these genes produce proteins that can improve blood sugar regulation and insulin levels throughout the body and so are associated with improved metabolic health. These genes were much more active when the men had fasted before exercise than when they had breakfasted.
The Best Thing to Eat Before a Workout? Maybe Nothing at All - The New York Times“If we just think of this in evolutionary terms,” he said, “our ancestors would have had to expend a great deal of energy through physical activity in order to hunt and gather food. So, it would be perfectly normal for the exercise to come first, and the food to follow.”
Astaxanthin compound found to switch on the FOX03 'Longevity Gene' in mice -- ScienceDaily"All of us have the FOXO3 gene, which protects against aging in humans," said Dr. Bradley Willcox, MD, Professor and Director of Research at the Department of Geriatric Medicine, JABSOM, and Principal Investigator of the National Institutes of Health-funded Kuakini Hawaii Lifespan and Healthspan Studies. "But about one in three persons carry a version of the FOXO3 gene that is associated with longevity. By activating the FOXO3 gene common in all humans, we can make it act like the "longevity" version. Through this research, we have shown that Astaxanthin "activates" the FOXO3 gene," said Willcox.
Long live FOXO: unraveling the role of FOXO proteins in aging and longevityAging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.
Alzheimer's gene neutralized by exerciseDr. Noordsy noted one particularly remarkable study in which researchers compared patients with and without the ApoE gene, which is linked strongly to late-onset Alzheimer's disease. In the study, patients who were ApoE-negative showed similarly low mean cortical binding potential, related to plaque buildup in the brain, regardless of whether they exercised or not. But although ApoE-positive individuals (n = 39) had values that were substantially higher, the ApoE-positive patients who exercised (n = 13) had values similar to those who did not carry the gene (Arch Neurol 2012;69:636-643). "You could look at these results and rightfully say physical exercise neutralizes your risk for developing Alzheimer's disease if you're ApoE positive," Dr. Noordsy said.
Exercise switches off genes for depression?intriguing 2015 study, physician Helmuth Haslacher and his colleagues at the Medical University of Vienna in Austria compared the mental health and genomes of 55 elderly marathon runners and endurance bicyclists with those of 58 nonathletes. Among the nonathletes, they found a statistically significant correlation between the number of depressive symptoms these individuals experienced and a particular gene variant that interferes with normal BDNF production. Among the athletes, however, there was no such correlation. The researchers concluded that by stimulating BDNF production, long-term, vigorous aerobic exercise might actually counteract a genetic susceptibility to depression.
Do children inherit drug protection from parents exposed to nicotine or drugs? Study suggests link between children and fathers -- ScienceDaily"Children born of fathers who have been exposed to nicotine are programmed to be not only more resistant to nicotine toxicity, but to other chemicals as well," said Dr. Rando, professor of biochemistry & molecular pharmacology. "If a similar phenomenon occurs in humans, this raises many important questions. For example, if your father smoked does that mean chemotherapy might be less effective for you? Are you more or less likely to smoke? It's important to understand what information is specifically being passed down from father to offspring and how that impacts us."
Loneliness actually hurts us on a cellular level - VoxIn 2007, Cole and a team of researchers at UCLA make a breakthrough in a small 14-participant study. The very cells of people who lived through periods of chronic loneliness looked different. More specifically, the white blood cells of people who suffered through chronic loneliness appeared to be stuck in a state of fear. Cole and his colleagues observed two main genetic differences between lonely and non-lonely people. 1) Genes that code for the body’s inflammation response are turned on to a degree not seen in non-lonely participants. “There is a huge hidden epidemic of loneliness, and disenfranchisement from the human race” Which isn’t good. “Inflammation is great at responding to acute injury, but if you have inflammation going chronically, it serves as a fertilizer for chronic diseases like atherosclerosis and cardio vascular disease, neurodegenerative diseases, and metastatic cancer,” he says. “That provides one reasonable biological explanation for why they might be at an increased risk for these diseases.” 2) “At the same time, in almost like a teeter-totter regulatory dynamic, we see down-regulated, or suppressed activity, in a block of genes involved in fending off against viral infections.” Those genes code for proteins known as type-1 interferons, which direct the immune system to kill viruses. This is a bit of a head-scratcher. Increasing the body’s inflammation response in the face of stress makes sense. It’s protective in the short term. But why would our bodies become less willing to attack viruses?
How hearing loss can change the way nerve cells are wired -- ScienceDailyIn mice whose ears were blocked, cells in the auditory nerve started to use their supplies of neurotransmitter more freely. They depleted their reserves of these chemicals rapidly each time a new auditory signal came in, and they decreased the amount of space within the cells that housed sac-like structures called vesicles -- biological storage tanks where neurotransmitter chemicals are kept. "When it's quiet, the demands on the auditory nerve cells are not as great," Xu-Friedman says. "So it makes sense that you would see these changes: You no longer need as much neurotransmitter, so why invest in a lot of storage? If you're not that active, you don't need a big gas tank. And you're not as afraid to use up what you have. This is one plausible explanation for what we observed." The changes in cellular structure and behavior were the opposite of what Xu-Friedman team's saw in a previous study that placed mice in a consistently noisy environment. In that project -- faced with an unusually high level of noise -- the mice's auditory nerve cells started to economize their resources, conserving supplies of neurotransmitter while increasing the storage capacity for the chemicals. "It looks like these effects are two sides of the same coin, and they might be the first hints of a general rule that nerve cells regulate their connections based on how active they are," Xu-Friedman says.
How internal circadian clocks in neurons encode external daily rhythms of excitability -- ScienceDailyMolecular clocks in cells throughout the body control many physiologic changes in a 24-hour day/night circadian rhythm -- among them the timing of sleep and wakefulness. The master pacesetter for those clocks resides in a tiny part of the human brain, where about 42,000 nerve cells spontaneously and independently maintain a 24-hour cycle through rhythmic internal surges and falls of biochemical signals. But nerve cells communicate to each other via external electrical impulses. So how do those internal biochemical clock signals get turned into changes in external electrical firing activity, the activity that spreads the pacesetter timing in those 42,000 cells throughout the brain and the rest of the body? Researchers led by Karen Gamble, Ph.D., associate professor in the University of Alabama at Birmingham Department of Psychiatry and Behavioral Neurobiology, have identified a key mechanism linking the two in a paper published today in Nature Communications. It involves the activity of a kinase enzyme called GSK3 that changes the excitability -- a technical term for the likelihood of a nerve cell to fire an electrical impulse -- of those neurons. Identification of this role for GSK3 raises clinical interest because GSK3 is the target of lithium and other mood-stabilizing drugs used to treat bipolar disorder. Also, the sodium channels that were found to be regulated by GSK3 are the target of riluzole, a drug used to treat amyotropic lateral sclerosis, known as ALS or Lou Gehrig's disease, as well as anxiety disorders and depression.
Teenage binge drinking can affect brain function of future offspring -- ScienceDailyIn the offspring of alcohol-exposed rats, researchers examined genes in the hypothalamus, a region of the brain involved in many functions, including reproduction, response to stress, sleep cycles and food intake. Researchers looked for molecular changes to DNA that would reverse the on-off switches in individual genes. They found 159 such changes in the offspring of binge-drinking mothers, 93 gene changes in the offspring of binge-drinking fathers and 244 gene changes in the offspring of mothers and fathers who both were exposed to binge drinking.
A Medical Mystery of the Best Kind: Major Diseases Are in Decline - The New York TimesSomething strange is going on in medicine. Major diseases, like colon cancer, dementia and heart disease, are waning in wealthy countries, and improved diagnosis and treatment cannot fully explain it. Scientists marvel at this good news, a medical mystery of the best sort and one that is often overlooked as advocacy groups emphasize the toll of diseases and the need for more funds. Still, many are puzzled. “It is really easy to come up with interesting, compelling explanations,” said Dr. David S. Jones, a Harvard historian of medicine. “The challenge is to figure out which of those interesting and compelling hypotheses might be correct.”
Study of Holocaust survivors finds trauma passed on to children's genes | Science | The GuardianThe team were specifically interested in one region of a gene associated with the regulation of stress hormones, which is known to be affected by trauma. “It makes sense to look at this gene,” said Yehuda. “If there’s a transmitted effect of trauma, it would be in a stress-related gene that shapes the way we cope with our environment.” They found epigenetic tags on the very same part of this gene in both the Holocaust survivors and their offspring, the same correlation was not found in any of the control group and their children.
Does Exercise Slow the Aging Process? - The New York TimesSpecifically, someone who participated in a single activity, earning them a 1, was about 3 percent less likely to have very short telomeres than someone who didn’t exercise at all. That risk declined more substantially if someone exercised more. People who reported two types of exercise were 24 percent less likely to have short telomeres; three types of exercise were 29 percent less likely; and those who had participated in all four types of activities were 59 percent less likely to have very short telomeres. Interestingly, these associations were strongest among people between the ages of 40 and 65, the researchers found, suggesting that middle age may be a key time to begin or maintain an exercise program if you wish to keep telomeres from shrinking
Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans. - PubMed - NCBIGlobal and genome-wide sperm DNA methylation was altered after 3 months of exercise training. DNA methylation changes occurred in genes related to numerous diseases such as schizophrenia and Parkinson's disease.
DRD4 gene, present in ~1/4 people, doubles alcohol consumption near heavy drinkersWhen confederates quaffed multiple alcoholic drinks, carriers of the gene variant consumed an average of almost two wine or beer servings, versus almost one serving for noncarriers.
Food Choices Change Our Gene ExpressionMore importantly, it turns out that the changes in the expression of our DNA that will favor either health or disease are, to significant degree, under our direct control. No doubt the notion that we have control of our genetic expression may well seem iconoclastic. But, more importantly, the idea that our choices, in terms of the foods we eat, the exercise we get, and the levels of stress in our day-to-day lives, all influence the expression of our DNA should be looked upon as representing profound empowerment.
Are habits (or nurture) actually just epigeniticsMolecular analyses of the collected tissue samples showed that the regulation and activity of clock genes was altered after one night of sleep loss. The activity of genes is regulated by a mechanism called epigenetics. This involves chemical alterations to the DNA molecule such as methyl groups -- a process called methylation -- which regulates how the genes are switched on or off. The researchers found that clock genes had increased numbers of such DNA marks after sleep loss. They also found that the expression of the genes, which is indicative of how much of the genes' product is made, was altered. "As far as we know, we are the first to directly show that epigenetic changes can occur after sleep loss in humans, but also in these important tissues," says Dr. Cedernaes. "It was interesting that the methylation of these genes could be altered so quickly, and that it could occur for these metabolically important clock genes," he continues.
Nevertheless, “if you believe that your father was symptomatic, then you probably have a vulnerability to depression or anxiety”, says Yehuda. “Chances are that there is a real link between your father’s symptoms and your own, and that your problems are not necessarily a function of a genetic transmission, but of an epigenetic one.”