Recent quotes:

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Aging 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 exercise

Dr. 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 - Vox

In 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 -- ScienceDaily

In 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 -- ScienceDaily

Molecular 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 -- ScienceDaily

In 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 Times

Something 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 Guardian

The 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 Times

Specifically, 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 - NCBI

Global 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 drinkers

When 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 Expression

More 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 epigenitics

Molecular 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.”