lroot on October 14th, 2017

Healthy Living

People who are overweight cut their life expectancy by two months for every extra kilogram (2.2 pounds) of weight they carry, research suggests.

A major study of the genes that underpin longevity has also found that education leads to a longer life, with almost a year added for each year spent studying beyond school.

Other key findings are that people who give up smoking, study for longer and are open to new experiences might expect to live longer.

Scientists at the University of Edinburgh analysed genetic information from more than 600,000 people alongside records of their parents’ lifespan.

Because people share half of their genetic information with each of their parents, the team were able to calculate the impact of various genes on life expectancy.

Lifestyle choices are influenced to a certain extent by our DNA/genes, for example, have been linked to increased alcohol consumption and addiction. The researchers were therefore able to work out which have the greatest influence on lifespan.

Their method was designed to rule out the chances that any observed associations could be caused by a separate, linked factor. This enabled them to pinpoint exactly which lifestyle factors cause people to live longer, or shorter, lives.

They found that cigarette smoking and traits associated with lung cancer had the greatest impact on shortening lifespan.

For example, smoking a packet of cigarettes per day over a lifetime knocks an average of seven years off life expectancy, they calculated. But smokers who give up can eventually expect to live as long as somebody who has never smoked.

Body fat and other factors linked to diabetes also have a negative influence on life expectancy.

The study also identified two new DNA differences that affect lifespan. The first is a gene that affects blood cholesterol levels and reduces lifespan by around eight months. The second is a gene linked to the immune system that adds around half a year to life expectancy.

The research, published in Nature Communications, was funded by the Medical Research Council.

Data was drawn from 25 separate population studies from Europe, Australia and North America, including the UK Biobank which is a major study into the role of genetics and lifestyle in health and disease.

Professor Jim Wilson, of the University of Edinburgh’s Usher Institute, said: “The power of big data and genetics allow us to compare the effect of different behaviours and diseases in terms of months and years of life lost or gained, and to distinguish between mere association and causal effect.”

Dr Peter Joshi, Chancellor’s Fellow at the University of Edinburgh’s Usher Institute, said: “Our study has estimated the causal effect of lifestyle choices. We found that, on average, smoking a pack a day reduces lifespan by seven years, whilst losing one kilogram of weight will increase your lifespan by two months.”

Reference: Peter K. Joshi, Nicola Pirastu, […], James F. Wilson. Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00934-5

Genes

Researchers at the Institute of Molecular Biology (IMB) in Mainz have made a breakthrough in understanding the origin of the aging process. They have identified that genes belonging to a process called autophagy, which is one of the cells most critical survival processes, promote health and fitness in young worms but drive the process of aging later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the aging process arises as a quirk of evolution. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.

Getting old is something that happens to everyone and nearly every species on this planet, but the question is: should it? In a recent publication in the journal Genes & Development titled “Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans,” Dr. Holger Richly’s lab at IMB has found some of the first genetic evidence that may put this question to rest.

According to Jonathan Byrne, co-lead author of the paper: “These AP genes had not been found before because it is incredibly difficult to work with already old animals. We were the first to figure out how to do this on a large scale. From a relatively small screen, we found a surprisingly large number of genes that seem to operate in an antagonistic fashion.” Previous studies had found genes that encourage aging while still being essential for development, but the 30 genes the IMB researchers found represent some of the first found promoting aging specifically only in old worms. “Considering we tested only 0.05 percent of all the genes in a worm this suggests there could be many more of these genes out there to find,” stated Byrne.

According to Thomas Wilhelm, the other co-lead author of the paper. “What was most surprising was what processes those genes were involved in.” Not content to provide just the missing evidence for a 60-year-old puzzle, Wilhelm and his colleagues went on to describe what a subset of these genes do in C. elegans and how they might be driving the aging process. “This is where the results really get fascinating,” emphasized Dr. Holger Richly, the principal investigator of the study. “We found a series of genes involved in regulating autophagy, which accelerate the aging process.” These results are surprising indeed as the process of autophagy is a critical recycling process in the cell and is usually required to live a normal full lifetime. Autophagy is known to become slower with age and the authors of this paper show that it appears to completely deteriorate in older worms. They demonstrate that shutting down key genes in the initiation of the process allows the worms to live longer compared with leaving it running crippled. “This could force us to rethink our ideas about one of the most fundamental processes that exist in a cell,” Richly explained. “Autophagy is nearly always thought of as beneficial even if it is barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together. It is classic AP: in young worms, autophagy is working properly and is essential to reach maturity, but after reproduction it starts to malfunction causing the worms to age,” he continued.

In a final revelation, Richly and his team were able to track the source of the pro longevity signals to a specific tissue, namely the neurons. By inactivating autophagy in the neurons of old worms they were not only able to prolong the worms life but they increased the total health of the worms dramatically. “Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age and you even live longer. That is what it is like for the worms,” said Thomas Wilhelm. “We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this keeps the muscles and the rest of the body in good shape. The net result is a 50 percent extension of life.”

While the authors do not yet know the exact mechanism causing the neurons to stay healthier for longer, this finding could have wide implications. “It is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases,” elaborated Thomas Wilhelm. While any such treatment would be a long way off, assuming such findings could be recapitulated in humans it offers a tantalising hope for being able to prevent disease and get younger and healthier while doing so.

Reference: Thomas Wilhelm, Jonathan Byrne, Rebeca Medina, Ena Kolundži?, Johannes Geisinger, Martina Hajduskova, Baris Tursun, Holger Richly. Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes & Development, 2017; 31 (15): 1561 DOI: 10.1101/gad.301648.117

lroot on September 20th, 2017

Nuts

A study recently published in the online version of the European Journal of Nutrition has found that people who include nuts in their diet are more likely to reduce weight gain and lower the risk of overweight and obesity.

The findings came to light after researchers at Loma Linda University School of Public Health and the International Agency for Research on Cancer (IARC) evaluated diet and lifestyle data from more than 373,000 individuals from 10 European countries between the ages of 25 and 70.

Senior investigator Joan Sabaté, MD, DrPH, director of the Center for Nutrition, Lifestyle and Disease Prevention at LLUSPH, said that many people have historically assumed that nuts an energy-dense, high-fat food are not a good choice for individuals who want to lose weight. The findings, however, contradict that assumption.

In their five-year study, Sabaté and junior investigator Heinz Freisling, PhD, a nutritional epidemiologist with the Nutritional Methodology and Biostatistics group at IARC headquarters in Lyons, France, found that participants gained a mean average of 2.1 kilograms during the five-year period of the study. However, participants who ate the most nuts not only had less weight gain than their nut-abstaining peers, but also enjoyed a 5 percent lower risk of becoming overweight or obese.

“To me, this confirms that nuts are not an obesogenic food,” Sabaté said.

The pair of researchers has evaluated nuts in the past and found that they are positively associated with a variety of health benefits, including healthy aging and memory function in seniors. This study, however, represents the first time they have investigated the relationship between nuts and weight on a large scale. Tree nuts included in the study were almonds, hazelnuts, pistachios and walnuts.

The team analyzed information on the dietary practices and body mass indexes of 373,293 participants, working with data gathered by the European Prospective Investigation into Cancer and Nutrition. Although Sabaté and Freisling extracted and analyzed the data and reported the findings, they were joined by 35 other research scientists from 12 European countries and Malaysia who reviewed the paper ahead of publication.

Sabaté recommends that people eat nuts more often, pointing out that they offer energy, good fats, protein, vitamins, minerals and phytochemicals.

“Eat nuts during your meal,” he suggested. “Put them at the center of your plate to replace animal products. They’re very satiating.”

Reference: Heinz Freisling, Hwayoung Noh, Nadia Slimani, Véronique Chajès, Anne M. May, Petra H. Peeters, Elisabete Weiderpass, Amanda J. Cross, Guri Skeie, Mazda Jenab, Francesca R. Mancini, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Verena A. Katzke, Tilman Kühn, Annika Steffen, Heiner Boeing, Anne Tjønneland, Cecilie Kyrø, Camilla P. Hansen, Kim Overvad, Eric J. Duell, Daniel Redondo-Sánchez, Pilar Amiano, Carmen Navarro, Aurelio Barricarte, Aurora Perez-Cornago, Konstantinos K. Tsilidis, Dagfinn Aune, Heather Ward, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Giovanna Masala, Claudia Agnoli, Franco Berrino, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H. Bas Bueno-de-Mesquita, Ulrika Ericson, Emily Sonestedt, Anna Winkvist, Tonje Braaten, Isabelle Romieu, Joan Sabaté. Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study. European Journal of Nutrition, 2017; DOI: 10.1007/s00394-017-1513-0

lroot on September 12th, 2017

Mexican Salamander

One of regenerative medicine’s most compelling questions is why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot. The answer may lie with the body’s innate immune system, according to a new study of heart regeneration in the axolotl, or Mexican salamander, an organism that takes the prize as nature’s champion of regeneration.

The study, which was conducted by James Godwin, Ph.D., of the MDI Biological Laboratory in Bar Harbor, Maine, found that the formation of new heart muscle tissue in the adult axolotl after a heart attack is dependent on the presence of macrophages, a type of white blood cell. When macrophages were depleted, the salamanders formed permanent scar tissue that blocked regeneration.

The study has significant implications for human health. Since salamanders and humans share many of the same genes, it’s possible that the ability to regenerate is also built into our genetic code.

Godwin’s research demonstrates that scar formation plays a critical role in blocking the program for regeneration. “The scar shoots down the program for regeneration,” he said. “No macrophages means no cardiac regeneration.”

Godwin’s goal is to activate regeneration in humans through the use of drug therapies derived from macrophages that would promote scar-free healing directly, or those that would trigger the genetic programs controlling the formation of macrophages, which in turn could promote scar-free healing. His team is already looking at molecular targets for drug therapies to influence these genetic programs.

“If humans could get over the fibrosis hurdle in the same way that salamanders do, the system that blocks regeneration in humans could potentially be broken,” Godwin explained. “We don’t know yet if it’s only scarring that prevents regeneration or if other factors are involved. But if we’re really lucky, we might find that the suppression of scarring is sufficient in and of itself to unlock our endogenous ability to regenerate.”

The prevailing view in regenerative biology has been that the major obstacle to heart regeneration in mammals is insufficient proliferation of cardiomyocytes, or heart muscle cells. But Godwin found that cardiomyocyte proliferation is not the only driver of effective heart regeneration. His findings suggest that research efforts should pay more attention to the genetic signals controlling scarring.

The extraordinary incidence of disability and death from heart disease, which is the world’s biggest killer, is directly attributable to scarring. When a human experiences a heart attack, scar tissue forms at the site of the injury. While the scar limits further tissue damage in the short term, over time its stiffness interferes with the heart’s ability to pump, leading to disability and ultimately to terminal heart failure.

In addition to regenerating heart tissue following a heart attack, the ability to unlock dormant capabilities for regeneration through the suppression of scarring also has potential applications for the regeneration of tissues and organs lost to traumatic injury, surgery and other diseases, Godwin said.

Godwin’s findings are a validation of the MDI Biological Laboratory’s unique research approach, which is focused on studying regeneration in a diverse range of animal models with the goal of gaining insight into how to trigger dormant genetic pathways for regeneration in humans. In the past year and a half, laboratory scientists have discovered three drug candidates with the potential to activate regeneration in humans.

“Our focus on the study of animals with amazing capabilities for regenerating lost and damaged body parts has made us a global leader in the field of regenerative medicine,” said Kevin Strange, Ph.D., MDI Biological Laboratory president. “James Godwin’s discovery of the role of macrophages in heart regeneration demonstrates the value of this approach: we won’t be able to develop rational and effective therapies to enhance regeneration in humans until we first understand regeneration works in animals like salamanders.”

Godwin, who is an immunologist, originally chose to look at the function of the immune system in regeneration because its role as the equivalent of a first responder at the site of an injury means that it is responsible for preparing the ground for tissue repairs. The recent study was a follow-up to an earlier study which found that macrophages also play a critical role in limb regeneration.

The next step is to study the function of macrophages in salamanders and compare them with their human and mouse counterparts. Ultimately, Godwin would like to understand why macrophages produced by adult mice and humans don’t suppress scarring in the same way as in axolotls and then identify molecules and pathways that could be exploited for human therapies.

Godwin holds a dual appointment with The Jackson Laboratory, also located in Bar Harbor, which is focused on the mouse as a model animal. The dual appointment allows him to conduct experiments that compare genetic programming in the highly regenerative animals used as models at the MDI Biological Laboratory with genetic programming in neonatal and adult mice.

Reference: J. W. Godwin, R. Debuque, E. Salimova, N. A. Rosenthal. Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape. npj Regenerative Medicine, 2017; 2 (1) DOI: 10.1038/s41536-017-0027-y

Adult Stem Cells

Scientists at The Scripps Research Institute (TSRI) have found a new approach to the “reprogramming” of ordinary adult cells into stem cells.

In a study published in an Advance Online paper in Nature Biotechnology, the TSRI scientists screened a library of 100 million antibodies and found several that can help reprogram mature skin-like cells into stem cells known as induced pluripotent stem cells (IPSCs).

Making IPSCs from more mature types of cells normally involves genetic engineering by inserting four transcription factor genes into the DNA of those cells. The new approach uses antibodies identified by the scientists that can be applied to mature cells where they bind to proteins on the cell surface as a substitute for three of the standard transcription factor gene insertions.

IPSCs that are made using genetic engineering have many unknown risks associated with them and are not currently utilized outside of research studies. This new discovery opens the possibility of taking a persons own cells, reverse aging them back into young stem cells and then using those to replace aged or damaged cells throughout the body.

“This result suggests that ultimately we might be able to make IPSCs without putting anything in the cell nucleus, which potentially means that these stem cells will have fewer mutations and overall better properties,” said study senior author Kristin Baldwin, associate professor in TSRI’s department of neuroscience.

IPSCs can be made from patients’ own cells, and have a multitude of potential uses in personalized cell therapies and organ regeneration. However, none of IPSCs’ envisioned clinical uses has yet been realized, in part because of the risks involved in making them.

The standard IPSC induction procedure, developed a decade ago and known as OSKM, involves the insertion into adult cells of genes for four transcription factor proteins: Oct4, Sox2, Klf4 and c-Myc. With these genes added and active, the transcription factor proteins they encode are produced and in turn reprogram the cells to become IPSCs.

One problem with this procedure is that this nuclear reprogramming typically yields a collection of IPSCs with variable properties. “This variability can be a problem even when we’re using IPSCs in the laboratory for studying diseases,” Baldwin said.

In contrast, during ordinary animal development, cell identity is altered by molecular signals that come in from outside the cell and induce changes in gene activity, without any risky insertions of DNA. To find natural pathways like these through which ordinary cells could be turned into IPSCs Baldwin and her laboratory teamed up with the TSRI laboratory of Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry. Lerner has helped pioneer the development and screening of large libraries of human antibodies for finding new antibody-based drugs and scientific probes.

In this case, the team, including graduate student Joel W. Blanchard and postdoctoral research associate Jia Xie, who were lead authors, set up a library of about 100 million distinct antibodies and used it to find any that could substitute for OSKM transcription factors.

In an initial set of experiments, the researchers tried to identify antibodies that can replace both Sox2 and c-Myc. They established a large population of mouse fibroblast cells — often used to make IPSCs in experiments — and inserted the genes for the other two transcription factors, Oct4 and Klf4. Next they added their huge library of antibody genes to the population of cells, such that each cell ended up containing the genes for one or more of the antibodies.

The scientists could then observe which of the cells began forming stem cell colonies indicating that one of the antibodies produced by those cells had successfully replaced the functions of Sox2 and c-Myc and triggered the switch in cell identity. Sequencing the DNA of these cells allowed the researchers to determine the antibodies responsible.

In this way, the TSRI team discovered two antibodies that can be substituted for both Sox2 and c-Myc, and in a similar set of tests they found two antibodies that can replace a third transcription factor, Oct4. The scientists showed that instead of inserting these transcription factor genes they could simply supply the antibodies to the fibroblast cells in culture.

In this initial study, the scientists were unable to find antibodies that replace the function of the fourth OSKM transcription factor, Klf4. However, Baldwin expects that with more extensive screening she and her colleagues eventually will find antibody substitutes for Klf4 as well. “That one I think is going to take us a few more years to figure out,” she said.

The antibody-screening approach in principle allows scientists not only to find antibodies that can replace OSKM transcription factors, but also to study the natural signaling pathways through which these antibodies work.

In a proof of this principle, the scientists found that one of the Sox2-replacing antibodies binds to a protein on the cell membrane called Basp1. This binding event blocks Basp1’s normal activity and thus removes the restraints on WT1, a transcription factor protein that works in the cell nucleus. WT1, unleashed, then alters the activity of multiple genes, ultimately including Sox2’s, to promote the stem cell state using a different order of events than when using the original reprogramming factors.

The TSRI researchers now plan larger, more complex antibody-screening studies using human cells rather than mouse cells.

Reference: Joel W Blanchard, Jia Xie, Nadja El-Mecharrafie, Simon Gross, Sohyon Lee, Richard A Lerner, Kristin K Baldwin. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries. Nature Biotechnology, 2017; DOI: 10.1038/nbt.3963

Ketogenic Foods

As more people live into their 80s and 90s, researchers have delved into the issues of health and quality of life during aging. A recent mouse study at the UC Davis School of Veterinary Medicine sheds light on those questions by demonstrating that a high fat, or ketogenic, diet not only increases longevity but also improves physical strength.

“The results surprised me a little,” said nutritionist Jon Ramsey, senior author of the paper that appears in the September issue of Cell Metabolism. “We expected some differences, but I was impressed by the magnitude we observed a 13 percent increase in median life span for the mice on a high fat vs high carb diet. In humans, that would be seven to 10 years. But equally important, those mice retained quality of health in later life.”

Ramsey has spent the past 20 years looking at the mechanics that lead to aging, a contributing factor to most major diseases that impact rodents and humans alike. While calorie restriction has been shown in several studies to slow aging in many animals, Ramsey was interested in how a high fat diet may impact the aging process.

Ketogenic diets have gained popularity for a variety of health benefit claims, but scientists are still teasing out what happens during ketosis, when carbohydrate intake is so low that the body shifts from using glucose as the main fuel source to fat burning and producing ketones for energy.

The study mice were split into three groups: a regular rodent high-carb diet, a low carb/high fat diet, and a ketogenic diet (89-90 percent of total calorie intake). Originally concerned that the high fat diet would increase weight and decrease life span, the researchers kept the calorie count of each diet the same.

“We designed the diet not to focus on weight loss, but to look at metabolism,” Ramsey said. “What does that do to aging?”

In addition to significantly increasing the median life span of mice in the study, the ketogenic diet increased memory and motor function (strength and coordination), and prevented an increase in age-related markers of inflammation. It had an impact on the incidence of tumors as well.

“In this case, many of the things we’re looking at aren’t much different from humans,” Ramsey said. “At a fundamental level, humans follow similar changes and experience a decrease in overall function of organs during aging. This study indicates that a ketogenic diet can have a major impact on life and health span without major weight loss or restriction of intake. It also opens a new avenue for possible dietary interventions that have an impact on aging.”

Reference: Megan N. Roberts, Marita A. Wallace, Alexey A. Tomilov, Zeyu Zhou, George R. Marcotte, Dianna Tran, Gabriella Perez, Elena Gutierrez-Casado, Shinichiro Koike, Trina A. Knotts, Denise M. Imai, Stephen M. Griffey, Kyoungmi Kim, Kevork Hagopian, Fawaz G. Haj, Keith Baar, Gino A. Cortopassi, Jon J. Ramsey, Jose Alberto Lopez-Dominguez. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metabolism, 2017; 26 (3): 539 DOI: 10.1016/j.cmet.2017.08.005

lroot on September 1st, 2017

fruit and vegetables

Nutrition has been linked to cognitive performance, but researchers have not pinpointed what underlies the connection. A new study by University of Illinois researchers found that monounsaturated fatty acids a class of nutrients found in olive oils, nuts and avocados are linked to general intelligence, and that this relationship is driven by the correlation between MUFAs and the organization of the brain’s attention network.

The study of 99 healthy older adults, recruited through Carle Foundation Hospital in Urbana, compared patterns of fatty acid nutrients found in blood samples, functional MRI data that measured the efficiency of brain networks, and results of a general intelligence test. The study was published in the journal NeuroImage.

“Our goal is to understand how nutrition might be used to support cognitive performance and to study the ways in which nutrition may influence the functional organization of the human brain,” said study leader Aron Barbey, a professor of psychology. “This is important because if we want to develop nutritional interventions that are effective at enhancing cognitive performance, we need to understand the ways that these nutrients influence brain function.”

“In this study, we examined the relationship between groups of fatty acids and brain networks that underlie general intelligence. In doing so, we sought to understand if brain network organization mediated the relationship between fatty acids and general intelligence,” said Marta Zamroziewicz, a recent Ph.D. graduate of the neuroscience program at Illinois and lead author of the study.

Studies suggesting cognitive benefits of the Mediterranean diet, which is rich in MUFAs, inspired the researchers to focus on this group of fatty acids. They examined nutrients in participants’ blood and found that the fatty acids clustered into two patterns: saturated fatty acids and MUFAs.

“Historically, the approach has been to focus on individual nutrients. But we know that dietary intake doesn’t depend on any one specific nutrient; rather, it reflects broader dietary patterns,” said Barbey, who also is affiliated with the Beckman Institute for Advanced Science and Technology at Illinois.

The researchers found that general intelligence was associated with the brain’s dorsal attention network, which plays a central role in attention-demanding tasks and everyday problem solving. In particular, the researchers found that general intelligence was associated with how efficiently the dorsal attention network is functionally organized used a measure called small-world propensity, which describes how well the neural network is connected within locally clustered regions as well as across globally integrated systems.

In turn, they found that those with higher levels of MUFAs in their blood had greater small-world propensity in their dorsal attention network. Taken together with an observed correlation between higher levels of MUFAs and greater general intelligence, these findings suggest a pathway by which MUFAs affect cognition.

“Our findings provide novel evidence that MUFAs are related to a very specific brain network, the dorsal attentional network, and how optimal this network is functionally organized,” Barbey said. “Our results suggest that if we want to understand the relationship between MUFAs and general intelligence, we need to take the dorsal attention network into account. It’s part of the underlying mechanism that contributes to their relationship.”

Barbey hopes these findings will guide further research into how nutrition affects cognition and intelligence. In particular, the next step is to run an interventional study over time to see whether long-term MUFA intake influences brain network organization and intelligence.

“Our ability to relate those beneficial cognitive effects to specific properties of brain networks is exciting,” Barbey said. “This gives us evidence of the mechanisms by which nutrition affects intelligence and motivates promising new directions for future research in nutritional cognitive neuroscience.”

Reference: Marta K. Zamroziewicz, M. Tanveer Talukdar, Chris E. Zwilling, Aron K. Barbey. Nutritional status, brain network organization, and general intelligence. NeuroImage, 2017; 161: 241 DOI: 10.1016/j.neuroimage.2017.08.043

lroot on August 14th, 2017

Aerobic Exercise

Scientists have observed that more aerobically fit individuals have better memories. To investigate this phenomenon, they used magnetic resonance elastography (MRE), which measures the firmness and elasticity of organs, and found that fit individuals had a firmer, more elastic hippocampus a region of the brain associated with memory.

“MRE is a technique that has been used in organs like the liver, where it can assess the tissue stiffness and offers a reliable, non-invasive method for diagnosing hepatic fibrosis,” explains Guoying Liu, Ph.D. Director of the NIBIB program on Magnetic Resonance Imaging. “This study now demonstrates the tremendous potential for MRE to provide new quantitative biomarkers for assessing brain health as it relates to physical fitness.”

The research was performed by Aron K. Barbey, Associate Professor, Departments of Psychology and Bioengineering at the University of Illinois at Urbana-Champaign, along with his colleagues at Illinois, and with collaborators from Northeastern University in Boston and the University of Delaware. Their results are reported in the March issue of the journal NeuroImage.

The work was based on well established observations of atrophy and reduced size of the hippocampus in cognitively declining seniors. Given that long-known phenomenon, the researchers were puzzled by the fact that in young adults there was a correlation between fitness and memory, but the size of the hippocampus was the same in both groups.

“Most of the work in this area has relied on changes in the size of the hippocampus as a measure of hippocampal health and function. However, in young adults, although we see an increase in memory in more aerobically fit individuals, we did not see differences in hippocampal size,” said Barbey. “Because size is a gross measure of the structural integrity of the hippocampus, we turned to MRE, which provides a more thorough and qualitative measure of changes associated with function in this case memory.”

The investigators explained that MRE gives a better indication of the microstructure of the hippocampus the structural integrity of the entire tissue. And it does this by basically “bouncing” the organ, very gently, and measuring how it responds.

MRE is often described as being similar to a drop of water hitting a still pond to create the ripples that move out in all directions. A pillow under the subject’s head generates harmless pulses, known as shear waves, that travel through the hippocampus. MRE instruments measure how the pulsed waves change as they move through the brain and those changes give an extremely accurate measure and a color-coded picture of the consistency of the tissue: soft, hard and stiff, or firm with some bounce or elasticity.

The healthy hippocampus is like a firm pillow that quickly bounces back into shape after you press your finger into it as opposed to a mushy pillow that would retain your finger mark and not rebound to its original shape.

The researchers studied 51 healthy adults: 25 men and 26 women ages 18-35. They measured the participants’ performance on a memory test as well as their aerobic fitness levels, and used MRE to measure the elasticity of the hippocampus.

They found that those with higher fitness levels also had more elastic tissue in the hippocampus and scored the best on memory tests. Given the many studies showing the association between hippocampal health and memory in seniors and children, which was based on the size of the hippocampus, the results strongly suggest that MRE is a method that reveals that there is also an association between the health of the hippocampus and memory in young adults.

Said Barbey, “MRE turned out to be a fantastic tool that enabled us to demonstrate the importance of the hippocampus in healthy young adults and the positive effect of fitness. We are excited about using MRE to look at other brain structures.”

“And, of course, if these results are more widely disseminated,” Barbey concludes, “they could certainly serve as tremendous motivation for people concerned about getting forgetful as they age, to get moving and try to stay fit.”

Reference: Hillary Schwarb, Curtis L. Johnson, Ana M. Daugherty, Charles H. Hillman, Arthur F. Kramer, Neal J. Cohen, Aron K. Barbey. Aerobic fitness, hippocampal viscoelasticity, and relational memory performance. NeuroImage, 2017; 153: 179 DOI: 10.1016/j.neuroimage.2017.03.061

lroot on August 11th, 2017

Sun

Sunbathers may want to avoid midnight snacks before catching some rays.

A study in mice from the O’Donnell Brain Institute and UC Irvine shows that eating at abnormal times disrupts the biological clock of the skin, including the daytime potency of an enzyme that protects against the sun’s harmful ultraviolet radiation.

Although further research is needed, the finding indicates that people who eat late at night may be more vulnerable to sunburn and longer term effects such as skin aging and skin cancer, said Dr. Joseph S. Takahashi, Chairman of Neuroscience at UT Southwestern Medical Center’s Peter O’Donnell Jr. Brain Institute.

“This finding is surprising. I did not think the skin was paying attention to when we are eating,” said Dr. Takahashi, also an Investigator with the Howard Hughes Medical Institute.

The study showed that mice given food only during the day an abnormal eating time for the otherwise nocturnal animals sustained more skin damage when exposed to ultraviolet B (UVB) light during the day than during the night. This outcome occurred, at least in part, because an enzyme that repairs UV-damaged skin xeroderma pigmentosum group A (XPA) shifted its daily cycle to be less active in the day.

Mice that fed only during their usual evening times did not show altered XPA cycles and were less susceptible to daytime UV rays.

“It is likely that if you have a normal eating schedule, then you will be better protected from UV during the daytime,” said Dr. Takahashi, holder of the Loyd B. Sands Distinguished Chair in Neuroscience. “If you have an abnormal eating schedule, that could cause a harmful shift in your skin clock, like it did in the mouse.”

Previous studies have demonstrated strong roles for the body’s circadian rhythms in skin biology. However, little had been understood about what controls the skin’s daily clock.

The latest research published in Cell Reports documents the vital role of feeding times, a factor that scientists focused on because it had already been known to affect the daily cycles of metabolic organs such as the liver.

The study found that besides disrupting XPA cycles, changing eating schedules could affect the expression of about 10 percent of the skin’s genes.

However, more research is needed to better understand the links between eating patterns and UV damage in people, particularly how XPA cycles are affected, said Dr. Bogi Andersen of University of California, Irvine, who led the collaborative study with Dr. Takahashi.

“It’s hard to translate these findings to humans at this point,” said Dr. Andersen, Professor of Biological Chemistry. “But it’s fascinating to me that the skin would be sensitive to the timing of food intake.”

Dr. Takahashi, noted for his landmark discovery of the Clock gene regulating circadian rhythms, is researching other ways in which eating schedules affect the biological clock. A study earlier this year reinforced the idea that the time of day food is eaten is more critical to weight loss than the amount of calories ingested. He is now conducting long-term research measuring how feeding affects aging and longevity.

Reference: 1Hong Wang, Elyse van Spyk, Qiang Liu, Mikhail Geyfman, Michael L. Salmans, Vivek Kumar, Alexander Ihler, Ning Li, Joseph S. Takahashi, Bogi Andersen. Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage. Cell Reports, 2017; 20 (5): 1061 DOI: 10.1016/j.celrep.2017.07.022

lroot on August 7th, 2017

Nonochip

Researchers at The Ohio State University Wexner Medical Center and Ohio State’s College of Engineering have developed a new technology, Tissue Nanotransfection (TNT), that can generate any cell type of interest for treatment within the patient’s own body. This technology may be used to repair injured tissue or restore function of aging tissue, including organs, blood vessels and nerve cells. Results of the regenerative medicine study were published in the journal Nature Nanotechnology.

“By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining,” said Dr. Chandan Sen, director of Ohio State’s Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State’s College of Engineering in collaboration with Ohio State’s Nanoscale Science and Engineering Center.

Researchers studied mice and pigs in these experiments. In the study, researchers were able to reprogram skin cells to become vascular cells in badly injured legs that lacked blood flow. Within one week, active blood vessels appeared in the injured leg, and by the second week, the leg was saved. In lab tests, this technology was also shown to reprogram skin cells in the live body into nerve cells that were injected into brain-injured mice to help them recover from stroke.

“This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you’re off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary,” said Sen, who also is executive director of Ohio State’s Comprehensive Wound Center.

TNT technology has two major components: First is a nanotechnology-based chip designed to deliver cargo to adult cells in the live body. Second is the design of specific biological cargo for cell conversion. This cargo, when delivered using the chip, converts an adult cell from one type to another, said first author Daniel Gallego-Perez, an assistant professor of biomedical engineering and general surgery who also was a postdoctoral researcher in both Sen’s and Lee’s laboratories.

TNT doesn’t require any laboratory-based procedures and may be implemented at the point of care. The procedure is also non-invasive. The cargo is delivered by zapping the device with a small electrical charge that’s barely felt by the patient.

“The concept is very simple,” Lee said. “As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So, this is the beginning, more to come.”

Researchers plan to start clinical trials next year to test this technology in humans, Sen said.

Reference: Daniel Gallego-Perez, Durba Pal, Subhadip Ghatak, Veysi Malkoc, Natalia Higuita-Castro, Surya Gnyawali, Lingqian Chang, Wei-Ching Liao, Junfeng Shi, Mithun Sinha, Kanhaiya Singh, Erin Steen, Alec Sunyecz, Richard Stewart, Jordan Moore, Thomas Ziebro, Robert G. Northcutt, Michael Homsy, Paul Bertani, Wu Lu, Sashwati Roy, Savita Khanna, Cameron Rink, Vishnu Baba Sundaresan, Jose J. Otero, L. James Lee, Chandan K. Sen. Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nature Nanotechnology, 2017; DOI: 10.1038/nnano.2017.134