How to Improve Sleep

As we age, we typically experience declines in the quality of our sleep. Mindfulness meditation is a self-administered approach that intentionally focuses one’s attention on the emotions, thoughts and sensations occurring in the present moment. David Black, from University of Southern California (California, USA), and colleagues enrolled 49 men and women, ages 55 years and older, whoe experienced moderately (or greater) disturbed sleep, who were divided into two groups. One group visited the study center for six weekly two-hour sessions of a course in Mindfulness Awareness Practices for daily living. Those included meditation, eating, walking, movement and friendly or loving-kindness practices. A certified teacher led the exercises and also instructed participants to meditate for five minutes daily, gradually increasing to 20 minutes daily. The other group attended six weeks of a sleep hygiene and education course, where they learned about sleep problems, and self-care methods for improving sleep, and weekly behavioral sleep hygiene strategies. Prior to the start of the six-week programs, the average sleep quality questionnaire score was 10. At the end of the study period, those in the meditation group demonstrated improvement in their sleep score by an average of 2.8 points, compared to 1.1 points in the sleep hygiene group. Among those in the meditation group, daytime impairments, including symptoms of insomnia, fatigue and depression, were improved as well. The study authors conclude that: “Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life.”


David S. Black, PhD, MPH1; Gillian A. O?Reilly, BS1; Richard Olmstead, PhD2; Elizabeth C. Breen, PhD2; Michael R. Irwin, MD2. Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances

Life Extension Genes Discovered

Out of a ‘haystack’ of 40,000 genes from three different organisms, scientists at ETH Zurich and a research consortium in Jena have found genes that are involved in physical ageing. If you influence only one of these genes, the healthy lifespan of laboratory animals is extended and possibly that of humans, too.

With advancements in molecular genetic methods in recent decades, the search for the genes involved in the aging process has greatly accelerated. Until now, this was mostly limited to genes of individual model organisms such as the C. elegans nematode, which revealed that around one percent of its genes could influence life expectancy. However, researchers have long assumed that such genes arose in the course of evolution and in all living beings whose cells have a preserved a nucleus from yeast to humans.

Combing through 40,000 genes

Researchers at ETH Zurich and the JenAge consortium from Jena have now systematically gone through the genomes of three different organisms in search of the genes associated with the aging process that are present in all three species and thus derived from the genes of a common ancestor. Although they are found in different organisms, these so-called orthologous genes are closely related to each other, and they are all found in humans, too.

In order to detect these genes, the researchers examined around 40,000 genes in the nematode C. elegans, zebra fish and mice. By screening them, the scientists wanted to determine which genes are regulated in an identical manner in all three organisms in each comparable aging stage young, mature and old; i.e. either are they upregulated or downregulated during aging.

As a measure of gene activity, the researchers measured the amount of messenger RNA (mRNA) molecules found in the cells of these animals. mRNA is the transcript of a gene and the blueprint of a protein. When there are many copies of an mRNA of a specific gene, it is very active; the gene is upregulated. Fewer mRNA copies, to the contrary, are regarded as a sign of low activity, explains Professor Michael Ristow, coordinating author of the recently published study and Professor of Energy Metabolism at ETH Zurich.

Out of this volume of information, the researchers used statistical models to establish an intersection of genes that were regulated in the same manner in the worms, fish and mice. This showed that the three organisms have only 30 genes in common that significantly influence the aging process.

Reduce gene activity, live longer

By conducting experiments in which the mRNA of the corresponding genes were selectively blocked, the researchers pinpointed their effect on the aging process in nematodes. With a dozen of these genes, blocking them extended the lifespan by at least five percent.

One of these genes proved to be particularly influential: the bcat-1 gene. “When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent,” says Ristow.

The researchers were also able to explain how this gene works: the bcat-1 gene carries the code for the enzyme of the same name, which degrades so-called branched-chain amino acids. Naturally occurring in food protein building blocks, these include the amino acids L-leucine, L-isoleucine and L-valine.

When the researchers inhibited the gene activity of bcat-1, the branched-chain amino acids accumulated in the tissue, triggering a molecular signalling cascade that increased longevity in the nematodes. Moreover, the timespan during which the worms remained healthy was extended. As a measure of vitality, the researchers measured the accumulation of aging pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced. All of these parameters improved when the scientists inhibited the activity of the bcat-1 gene.

The scientists also achieved a life-extending effect when they mixed the three branched-chain amino acids into the nematodes’ food. However, the effect was generally less pronounced because the bcat-1 gene was still active, which meant that the amino acids continued to be degraded and their life-extending effects could not develop as effectively.

Conserved mechanism

Ristow has no doubt that the same mechanism occurs in humans. “We looked only for the genes that are conserved in evolution and therefore exist in all organisms, including humans,” he says.

In the present study, he and his Jena colleagues from the Leibniz Institute on Aging, the Leibniz Institute for Natural Product Research and Infection Biology, the Jena University Hospital and the Friedrich Schiller University purposefully opted not to study the impact on humans. But a follow-up study is already being planned. “However we cannot measure the life expectancy of humans for obvious reasons,” says the ETH professor. Instead, the researchers plan to incorporate various health parameters such as cholesterol or blood sugar levels in their study to obtain indicators on the health status of their subjects.

Health costs could be massively reduced

Ristow says that the multiple branched-chain amino acids are already being used to treat liver damage and are also added to sport nutrition products. “However, the point is not for people to grow even older, but rather to stay healthy for longer,” says the internist. The study will deliver important indicators on how the aging process could be influenced and how age-related diseases such as diabetes or high blood pressure could be prevented. In light of unfavourable demographics and steadily increasing life expectancy, it is important to extend the healthy life phase and not to reach an even higher age that is characterised by chronic diseases, argue the researchers. With such preventive measures, an elderly person could greatly improve their quality of life while at the same time cutting their healthcare costs by more than half.

Blood and Aging

We have all heard those particularly haunting tales about witches remaining ever youthful by imbibing a young woman?s blood, but until a few years ago these tales were only told to frighten children before bed. Last year, SAGE reported on a study where the blood of a young mouse was sufficient to rejuvenate an older mouse. This study lent credence to the idea that there must be something substantially different in young blood compared to old.

To examine the changes that occur in blood as an individual ages, Dr. Andrew Johnson?s lab, at NIH/NHLBI (National Institute of Health/National Heart, Lung and Blood Institute) conducted an extensive study using thousands of patient blood samples, the study was then replicated, further verifying the results.

The researchers chose to analyze the blood samples transcriptome, a measurement of the RNA transcripts from each gene. The compilation of RNA transcripts is a reflection of the relative expression levels of the genome at a given point in time. The choice to examine the transcriptome was pivotal, as all the cells in an organism will have the same DNA and this DNA does not generally change during the person?s lifetime, thus making DNA genomic analysis less useful for an age-related study. What does change over a person?s lifetime is modifications of DNA, which genes are expressed from the DNA and the relative levels of expression of each gene.

The study, which has been published in Nature Communications, used certain types of blood cells and brain tissue to examine the age-associated changes in gene expression. In a remarkable show of replication, the study was initially performed with blood samples from individuals of European ancestry and then replicated in additional European ancestry samples, totaling an amazing 14,983 individual European ancestry samples. The study was then extended to various ethnic groups, including samples from individuals of Hispanic, African, or Native American ancestry. The study identified 1,497 genes in blood cells and/or brain tissue that showed significantly differential expression patterns in older individuals when compared to younger individuals.

The expression of the gene can either be negatively correlated (expressed at a lower level) or positively correlated (expressed at a higher level) in relation to chronological age. There were three distinct groups of genes that were negatively correlated with chronological age. The first group included three subgroups: ribosomal genes (factories on which a RNA is translated into a protein), mitochondrial genes (energy factories of the cells), and genes associated with DNA replication and repair (DNA maintenance and fidelity). All of the genes associated with these subgroups are vitally important to the health of a cell and tissue. The second large group consisted of genes associated with immunity. The third large group was composed of genes that code for the actual ribosomal subunits. Decreased gene expression could help explain the decreased ?health? of older cells and increased mutation rates in older cells. There were also four groups of genes positively correlated with age, which were focused on cellular structure, immunity, fatty acid metabolism, and lysosome activity. Several of the genes in these clusters had been previously identified in other age-related screens in various model organisms, further supporting this study?s methods and findings.

Another interesting finding in this study involved epigenetic patterns, specifically methylation on cytosines (one of the four nucleotide bases in DNA) and the predictive. Epigenetics can be thought of as the ?grammar? of DNA, as it doesn?t change the underlying pattern of DNA base pairs, but rather instructs how a gene is to be expressed. Methylation on cytosines is an epigenetic mark that can have a regulatory effect on how or if a gene is expressed. Methylation patterns are also dynamic, meaning that this pattern can change over time. This study showed that those genes whose expression pattern changed with age were highly enriched for the presence of regulatory cytosines. This could indicate how gene expression is controlled as the individual ages. There are several targeted methylation therapies in development that might potentially offer the ability to effectively and safely alter these methylation patterns for therapeutic purposes. The authors found that by combining the transcriptomic expression patterns and the epigenetic patterns a ?chronological? age predictor could be used to better understand an individual?s ?age? in terms of health. Further refinement is needed, but this type of predictor could have a substantial impact on prediction, diagnosis and treatment of individuals, perhaps even allowing for preventive treatments before symptoms progress to disease level changes.

The sheer magnitude of this study, from the number of samples to the ethnic diversity of the participants, makes it a pioneer in the rapidly expanding field of transcriptomics. Until a few years ago, the methods and budgets did not exist for such a study to take place, but as the technology continues to increase, costs decline and more data will become available, enhancing our understanding of aging and allowing for us to better cope with age-associated changes. The 1,497 genes identified as being associated with chronological age offer a plethora of new targets from which we can better understand the aging process and age-related diseases. With the current progress being made in the gene therapy and drug fields it is possible that some of these 1,497 genes could potentially be manipulated to ameliorate many age-related diseases.

Coconut Oil Decreases Funguses in the Digestive System

A new inter-disciplinary study led by researchers at Tufts University found that coconut oil effectively controlled the overgrowth of a fungal pathogen called Candida albicans (C. albicans) in mice. In humans, high levels of C. albicans in the gastrointestinal tract can lead to bloodstream infections, including invasive candidiasis. The research, published in mSphere, suggests that it might be possible to use dietary approaches as an alternative to antifungal drugs in order to decrease the risk of infections caused by C. albicans.

C. albicans, a common fungal pathogen, is part of the gastrointestinal tract’s normal flora and well-regulated by the immune system. When the immune system is compromised, however, the fungus can spread beyond the GI tract and cause disease. Systemic infections caused by C. albicans can lead to invasive candidiasis, which is the fourth most common blood infection among hospitalized patients in the United States according to the CDC. The infection is most common among immunocompromised patients, including premature infants and older adults.

Antifungal drugs can be used to decrease and control C. albicans in the gut and prevent it from spreading to the bloodstream, but repeated use of antifungal drugs can lead to drug resistant-strains of fungal pathogens. In order to prevent infections caused by C. albicans, the amount of C. albicans in the gastrointestinal tract needs to be reduced.

The team, led by microbiologist Carol Kumamoto and nutrition scientist Alice H. Lichtenstein, investigated the effects of three different dietary fats on the amount of C. albicans in the mouse gut: coconut oil, beef tallow and soybean oil. A control group of mice were fed a standard diet for mice. Coconut oil was selected based on previous studies that found that the fat had antifungal properties in the laboratory setting.

A coconut oil-rich diet reduced C. albicans in the gut compared to a beef tallow-or soybean oil-rich diet. Coconut oil alone, or the combination of coconut oil and beef tallow, reduced the amount of C. albicans in the gut by more than 90% compared to a beef tallow-rich diet.

“Coconut oil even reduced fungal colonization when mice were switched from beef tallow to coconut oil, or when mice were fed both beef tallow and coconut oil at the same time. These findings suggest that adding coconut oil to a patient’s existing diet might control the growth of C. albicans in the gut, and possibly decrease the risk of fungal infections caused by C. albicans,” said Kumamoto, Ph.D., a professor of molecular biology and microbiology at Tufts University School of Medicine and member of the molecular microbiology and genetics program faculties at the Sackler School of Graduate Biomedical Sciences.

“Food can be a powerful ally in reducing the risk of disease,” said Alice H Lichtenstein, D.Sc., director of the Cardiovascular Nutrition Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “This study marks a first step in understanding how life-threatening yeast infections in susceptible individuals might be reduced through the short-term and targeted use of a specific type of fat. As exciting as these findings are, we have to keep in mind that the majority of adult Americans are at high risk for heart disease, the number one killer in the U.S. The potential use of coconut oil in the short term to control the rate of fungal overgrowth should not be considered a prophylactic approach to preventing fungal infections.”

“We want to give clinicians a treatment option that might limit the need for antifungal drugs. If we can use coconut oil as a safe, dietary alternative, we could decrease the amount of antifungal drugs used, reserving antifungal drugs for critical situations,” said first author Kearney Gunsalus, Ph.D., an Institutional Research and Academic Career Development (IRACDA) postdoctoral fellow at the Sackler School in Kumamoto’s lab.


Carol Kumamoto et al. Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans. mSphere, November 2015 DOI: 10.1128/mSphere.00020-15

Health Benefits of Coconut Oil


A simple tablespoon daily of coconut oil could promote weight loss and improve cardiovascular health, reveals a new clinical study.

A new study titled, A coconut extra virgin oil-rich diet increases HDL cholesterol and decreases waist circumference and body mass in coronary artery disease patients, holds great promise in those suffering from overweight, obesity, and heightened cardiovascular disease risk, and against which pharmaceutical approaches often fail.

Coconut oil was once considered a bad fat, as it contains saturated fatty acids which conventional nutritionists did not distinguish from synthetically produced ones such as margarine. We know far better now, and increasingly, natural sources of saturated fats are gaining appreciation as not only not-bad, but actually beneficial, particularly for the brain.

The new study evaluated the health effects of a nutritional treatment with extra virgin coconut oil, focusing primarily on how it affects HDL cholesterol and a range of anthropmetric measurements (e.g. body weight, size, circumference).

The average age of the participants was 62.4 years, with 70% of elderly individuals, and 63.2% of males. All of them were hypertensive and 94.5% had blood lipid profiles indicating dyslipidemia and on standard, cholesterol lowering drug treatment.

In the first phase, a three month period, 136 enrollees were put on a standardized diet. From the third month onward, the 116 who completed the first phase were place in two intervention groups: 22 remained on the diet, and 92 were put on the diet + 13 ml (.43 ounces) daily of extra virgin coconut oil, which is equivalent to about 14 grams, or about 1 Tablespoon (15 grams).

The results of the the three-month coconut oil intervention showed that relative to the standard diet, the coconut group saw a decrease in all six of the bodily parameters measured, including:

Weight: -.6 kilograms (1.322 pounds)
Body Mass Index: ? .2 kg/m2
Waist Circumference: -2.1 cm
Neck Perimeter: -4 cm

This study is far more powerful than may first meet the eye. For instance, at present, pharmaceutical interventions to raise HDL cholesterol lack solid scientific support. Only yesterday, I reported on a new JAMA review which revealed an astounding number of medical procedures have no benefit, even harm, wherein it was concluded that , In patients with low HDL-C levels who are treated with statins, there is no clinical benefit to HDL-C targeted therapies. Considering the fact that pharmaceutical interventions to lower HDL cholesterol have a wide range of serious side effects, the new finding that coconut oil may provide a natural alternative with side benefits, is all the more encouraging.

Additionally, midsection fat, also known as abdominal obesity, is a serious risk factor for cardiovascular events and cardiac mortality. In fact, a 2007 study published in the journal Circulation found that of three risk factors evaluated for heart attack, namely, abdominal obesity, abnormal lipids, and smoking, abdominal obesity was the most powerful: 48.5%, versus 40.8% for abnormal lipids, and 38.4% for smoking.

When one considers these two factors, any safe, diet-based lifestyle modification that can safely raise HDL-C cholesterol, and reduce midsection fat and related anthropometric parameters such as BMI and midsection circumference, is a home run.

This is, of course, not the first time we have reported on the powerful health benefits of coconut oil. In fact, it doesn’t take months, or even days, to observe positive changes in certain populations. We reported previously on what can only be described as an amazing study where just one dose of coconut oil derived medium chain triglycerides produced positive cognitive changes in Alzheimer’s patients in only 90 minutes. You can read about it in greater detail here: MCT Fats Found In Coconut Oil Boost Brain Function In Only One Dose.

Why Does Caloric Restriction Increase Lifespan?

As medicine has improved, we are increasing our ability to treat disease and improve longevity. The deterioration of the body with age, though, is a whole other matter.

Scientists suggest that all we might need is some “house-keeping” of the brain, according to research just published in an early edition of the journal PNAS by a Portuguese team from the Centre for Neuroscience and Cell Biology (CNC) of the University of Coimbra.

The researchers might have also solved a 70-year old mystery: How can calorie restriction (a diet with low calories without malnutrition) delay ageing and increase longevity in animals from dogs to mice?

In their new study, Claudia Cavadas and her group have discovered that the key to this diet appears to be its ability to increase autophagy – the mechanism that recycles unwanted molecules in the cells, thereby avoiding malfunction in the hypothalamus, which has just been identified as the “control centre” for ageing. They also have identified the molecule that controls the process. It’s called neuropeptide Y (NPY), and its discovery raises the possibility that NPY could be used to develop techniques to control aging instead of just treating its consequences, like we do now.

The discovery may be a key to stopping the development of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s, a huge step forward, considering that science has thus far been incapable of treating, stopping or even fully understanding them. And in a rapidly aging world, a better control of these kinds of problems can prove crucial for everyone’s survival.

In fact, according to the UN, in less than a decade, 1 billion people will be older than 60. In Japan, more than 30% of the population is older than 60 years old, and in Europe, 16% of the population is over 65. So it is clear that our increasingly aging population needs to be kept as healthy and active as possible, or it will be financially and socially impossible for the world to cope. It is no surprise, then, that research to understand and control the deteriorating effects of aging is now a priority.

One thing that has been clear for a while now is that autophagy (or better, a reduction of it) is at the centre of the aging process. Low levels of autophagy?that is, impaired cellular “house-keeping”? is linked to ageing and age-related neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and Huntington’s diseases. This is easily explained as autophagy clears the cellular “debris” keeping neurons in good working order. The importance of the process in the brain is no surprise, since neurons have a lower ability to replenish themselves once they die or malfunction.

But about a year ago, there was a remarkable discovery that changed the field: The hypothalamus, which is a brain area that regulates energy and metabolism, was identified as the control centre for whole-body aging.

To Cavadas and her group, who have worked on aging and neuroscience for a long time, this was particularly exciting. They knew calorie restriction delayed aging and increased longevity and increased autophagy in the hypothalamus; but they also knew that it did the same to NPY and that mice without NPY did not respond to calorie restriction. Furthermore NPY, like autophagy, diminishes with age. All this, together with the discovery of the new role of the hypothalamus, suggested that this brain area and NPY were the key to the rejuvenating effects of calorie restriction.

So now all that was left was to connect the dots, and for that, the researchers started by taking neurons from the hypothalami of mice and growing them in a medium that mimicked a low caloric diet. They then measured rates of autophagy. As expected, autophagy levels in this calorie-restriction-like medium were much higher than normal, unless NPY was blocked, in which case the medium had no consequences on the neurons. So calorie restriction effect on the hypothalamic autophagy appeared to depend on NPY. To confirm this, the researchers then tested mice genetically modified to produce higher than normal quantities of NYP in their hypothalami. As expected, this led to higher levels of autophagy.

So calorie restriction seems to work by increasing the levels of NPY in the hypothalamus, which in turn triggers an increase in autophagy in its neurons, “rejuvenating” them and delaying aging symptoms. Cavadas and colleagues also identified the biochemical pathways involved in the NPY effect. This, however, is not the whole story, as it still does not explain why in some species, such as wild mice, calorie restriction has no effect.

But by adding a new piece to the puzzle of aging, the group’s research is an important step toward delaying the the body’s deterioration, allowing individuals to have healthier lives until the end, particularly with regard to the brain. Age-related neurodegenerative diseases seem to be unstoppable at the moment, and are not only an economic but also a huge social burden as patients became totally dependent on their families or the state.

In fact, in the US, more than 5 million people already suffer from Alzheimer’s (1 million have Parkinson’s), while in the UK this number is reaching 1 million. Just in the care of dementia patients, the UK health system is spending more than ?26 billion yearly (the equivalent to 38 billion dollars or 36 billion Euros). Age-related neurodegenerative diseases are already the fourth highest disease burden in the western world, and growing.

It will be interesting to further understand the long-debated mystery of the mechanism behind calorie restriction, and test to see if it works on humans as some believe (it does not work, for example, on wild mice). In fact, during World War II in Europe, when food was short, there was a sharp decrease in heart diseases (which are age-related) that rapidly rose once the war ended. The same reduction is observed in Okinawa island in Japan, where people eat on average less 30% of calories than the rest of the country. Whether a coincidence or not, it should be interesting to know what that that means in our “junk-food” society.

New Discovery About Blood Stem Cells


Stem-cell scientists led by the University of Toronto’s Dr. John Dick have discovered a completely new view of how human blood is made, upending conventional dogma from the 1960s.

The findings, published online Nov. 5 in the journal Science, prove ?that the whole classic ?textbook? view we thought we knew doesn?t actually even exist,? says Professor Dick, the principal investigator.

Dick is senior scientist at Princess Margaret Cancer Centre, University Health Network (UHN), and a professor in the department of molecular genetics at U of T.

?Instead, through a series of experiments we have been able to finally resolve how different kinds of blood cells form quickly from the stem cell which is the most potent blood cell in the system and not further downstream as has been traditionally thought,? says Dick, who holds a Canada Research Chair in Stem Cell Biology and is also director of the Cancer Stem Cell Program at the Ontario Institute for Cancer Research.

The research also topples the textbook view that the blood development system is stable once formed. Not so, says Dr. Dick. ?Our findings show that the blood system is two-tiered and changes between early human development and adulthood.?

Co-authors Dr. Faiyaz Notta and Dr. Sasan Zandi from the Dick lab write that in redefining the architecture of blood development, the research team mapped the lineage potential of nearly 3,000 single cells from 33 different cell populations of stem and progenitor cells obtained from human blood samples taken at various life stages and ages.

?Our discovery means we will be able to understand far better a wide variety of human blood disorders and diseases?

For people with blood disorders and diseases, the potential clinical utility of the findings is significant, unlocking a distinct route to personalizing therapy.

Dick says: ?Our discovery means we will be able to understand far better a wide variety of human blood disorders and diseases ? from anemia, where there are not enough blood cells, to leukemia, where there are too many blood cells. Think of it as moving from the old world of black-and-white television into the new world of high definition.?

There are also promising implications for advancing the global quest in regenerative medicine to manufacture mature cell types such as platelets or red blood cells by engineering cells (a process known as inducing pluripotent stem cells), says Dick, who collaborates closely with Professor Gordon Keller of the department of medical biophysics at U of T and a director of UHN?s McEwen Centre for Regenerative Medicine.

?By combining the Keller team?s ability to optimize induced pluripotent stem cells with our newly identified progenitors that give rise only to platelets and red blood cells, we will be able develop better methods to generate these mature cells,? he says. Currently, human donors are the sole source of platelets ? which cannot be stored or frozen ? for transfusions needed by many thousands of patients with cancer and other debilitating disorders.

Today?s discovery builds on Dick?s breakthrough research in 2011, also published in Science, when the team isolated a human blood stem cell in its purest form ? as a single stem cell capable of regenerating the entire blood system.

?Four years ago, when we isolated the pure stem cell, we realized we had also uncovered populations of stem-cell like ?daughter? cells that we thought at the time were other types of stem cells,? says Dick. ?When we burrowed further to study these ?daughters?, we discovered they were actually already mature blood lineages. In other words, lineages that had broken off almost immediately from the stem cell compartment and had not developed downstream through the slow, gradual ?textbook? process.

?So in human blood formation, everything begins with the stem cell, which is the executive decision-maker quickly driving the process that replenishes blood at a daily rate that exceeds 300 billion cells.?

For 25 years, Dick?s research has focused on understanding the cellular processes that underlie how normal blood stem cells work to regenerate human blood after transplantation and how blood development goes wrong when leukemia arises. His research follows on the original 1961 discovery of the blood stem cell by Princess Margaret Cancer Centre scientists Dr. James Till and the late Dr. Ernest McCulloch, which formed the basis of all current stem-cell research.

Better Sleep and Tai Chi Help Produce Healthy Inflammation Levels

A new study published in the current issue of Biological Psychiatry reports that treatment for insomnia, either by cognitive behavioral therapy or the movement meditation tai chi, help produce healthy inflammation levels in older adults over 55 years of age.

“Behavioral interventions that target sleep reduce inflammation and represent a third pillar, along with diet and physical activity, to promote health and possibly reduce the risk of age-related morbidities including depression,” said Dr. Michael Irwin, who conducted this work along with his colleagues at the Cousins Center for Psychoneuroimmunology at the University of California Los Angeles.

For this study, the researchers recruited 123 older adults with insomnia who were randomized to receive one of 3 types of classes: cognitive behavioral therapy for insomnia, the movement meditation tai chi, or a sleep seminar (the control condition).

They found that treatment of sleep disturbance with cognitive behavioral therapy for insomnia reduces insomnia symptoms, reduces levels of a systemic marker of inflammation called C-reactive protein, and reverses activation of molecular inflammatory signaling pathways. These benefits were maintained throughout the study’s 16-month follow-up period.

Tai chi, a lifestyle intervention that targets stress that can lead to insomnia, was also found to reduce inflammation, and did so by reducing the expression of inflammation at the cellular level and by reversing activation of inflammatory signaling pathways. The reduction of cellular inflammation was also maintained during the 16-month follow-up.

Those participants assigned to the sleep seminar classes showed no significant changes in inflammatory markers, as expected.

These results provide an evidence-based molecular framework to understand how behavioral interventions that target sleep may reduce inflammation and promote health.

“This study suggests that there are behavioral approaches that can improve sleep, reduce stress, and thereby improve health,” commented Dr. John Krystal, Editor of Biological Psychiatry. “It is a reminder, once again, that there is no health without mental health.”

Growing Replacement Tissues and Organs for Transplantation with 3D Printer

Using sugar, silicone, and a 3D printer, bioengineers at Rice University and surgeons at the University of Pennsylvania have created an implant with an intricate network of blood vessels that points toward a future of growing replacement tissues and organs for transplantation.

The research may provide a method to overcome one of the biggest challenges in regenerative medicine, i.e., how to deliver oxygen and nutrients to all cells in an artificial organ or tissue implant that takes days or weeks to grow in the lab prior to surgery.

The new study was performed by a research team led by Jordan Miller, Ph.D., assistant professor of bioengineering at Rice, and Pavan Atluri, M.D., assistant professor of surgery at Penn. The study showed that blood flowed normally through test constructs that were surgically connected to native blood vessels. The study (?In vivo anastomosis and perfusion of a 3D printed construct containing microchannel networks?) was published in Tissue Engineering Part C: Methods.

Dr. Miller said one of the hurdles of engineering large artificial tissues, such as livers or kidneys, is keeping the cells inside them alive. Tissue engineers have typically relied on the body’s own ability to grow blood vessels, for example, by implanting engineered tissue scaffolds inside the body and waiting for blood vessels from nearby tissues to spread to the engineered constructs. Dr. Miller noted that that process can take weeks, and cells deep inside the constructs often starve or die from lack of oxygen before they’re reached by the slow-approaching blood vessels.

“We had a theory that maybe we shouldn’t be waiting,” he explained. “We wondered if there were a way to implant a 3D printed construct where we could connect host arteries directly to the construct and get perfusion immediately. In this study, we are taking the first step toward applying an analogy from transplant surgery to 3D printed constructs we make in the lab.”

Dr. Miller and his team thought long-term about what the needs would be for transplantation of large tissues made in the laboratory. “What a surgeon needs in order to do transplant surgery isn’t just a mass of cells; the surgeon needs a vessel inlet and an outlet that can be directly connected to arteries and veins,” he added.

The research team worked together to develop a proof-of-concept construct, a small silicone gel about the size of a small candy gummy bear, using 3D printing. But rather than printing a whole construct directly, the scientists fabricated sacrificial templates for the vessels that would be inside the construct.

It’s a technique pioneered by Dr. Miller in 2012 and inspired by the intricate sugar glass cages crafted by pastry chefs to garnish desserts.

Using an open-source 3D printer that lays down individual filaments of sugar glass one layer at a time, the researchers printed a lattice of would-be blood vessels. Once the sugar hardened, the investigators placed it in a mold and poured in silicone gel. After the gel cured, Dr. Miller’s team dissolved the sugar, leaving behind a network of small channels in the silicone.

“They don’t yet look like the blood vessels found in organs, but they have some of the key features relevant for a transplant surgeon,” said Dr. Miller. “We created a construct that has one inlet and one outlet, which are about 1 millimeter in diameter, and these main vessels branch into multiple smaller vessels, which are about 600 to 800 microns.”

Collaborating surgeons at Penn in Dr. Atluri’s group connected the inlet and outlet of the engineered gel to a major artery in a small animal model. Using Doppler imaging technology, the team observed and measured blood flow through the construct and found that it withstood physiologic pressures and remained open and unobstructed for up to three hours.

“This study provides a first step toward developing a transplant model for tissue engineering where the surgeon can directly connect arteries to an engineered tissue,” said Dr. Miller. “In the future we aim to utilize a biodegradable material that also contains live cells next to these perfusable vessels for direct transplantation and monitoring long term.”

Important Anti-aging Protein Studied by Harvard Team

Back in the 1950s in a weird, vampiric experiment, scientists first showed that connecting the circulatory systems of old and young mice seems to rejuvenate the more elderly animals. A handful of labs have recently been racing to find factors in young blood that may explain this effect. Now, a Harvard University group that claims to have found one such antiaging protein has published a study countering critics who dismissed the work on the molecule as flawed.

Harvard stem cell biologist Amy Wagers, cardiologist Richard Lee of the Harvard-affiliated Brigham and Women?s Hospital in Boston, and their colleagues claim that a specific protein, GDF11, may explain young blood?s beneficial effects. They have reported that blood levels of GDF11 drop in mice as the animals get older and that injecting old mice with GDF11 can partially reverse age-related thickening of the heart. In two papers last year in Science, Wagers and collaborators also reported that GDF11 can rejuvenate the rodents? muscles and brains.

Last May, however, a group led by muscle disease researcher David Glass of the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts, reported that the antibody the Harvard team used to measure levels of GDF11 also detected myostatin (also known as GDF8), a similar protein that hinders muscle growth. The Novartis group concluded from a different assay that GDF11 levels in blood actually rise with age in rats and people. And in their lab, GDF11 injections inhibited muscle regeneration in young mice.

Now, the Wagers and Lee group says the assay Novartis used to detect GDF11 and GDF8 was itself flawed. They found that the main protein detected by the antibody test is immunoglobulin, another protein that rises in blood level with age. Mice lacking the gene for immunoglobulin tested negative for the active form of GDF11/8 that the Novartis assay was thought to reveal, they report today online in Circulation Research.

?They actually had very consistent findings to ours with respect to the blood levels of GDF11/8 with the antibody we all used,? Wagers says. But ?their interpretation was confused by this case of mistaken identity.? A recently published study by University of California, San Francisco, researchers finding that GDF11/8 blood levels decline with age in people and are low in those with heart disease supports the contention that GDF11 has an antiaging role, her paper notes.

The Harvard team?s paper also disputes a recent study in which cardiac physiologist Steven Houser?s group at Temple University in Philadelphia, Pennsylvania, found that GDF11 injections have no effect on heart thickness in older mice. The problem, according to Wagers, is that commercially purchased GDF11 can vary in the actual level and activity of protein. ?It wasn?t something that affected us early on, but we figured out it was an issue,? she says. That lot-to-lot variability likely explains why the Houser group didn?t see any effects from GDF11 at the same apparent dose the Harvard group reported using, she adds. (Lee says his group now suspects that the dose was higher than they realized.)

To back up their earlier results, Wagers and collaborators again show in the new paper that daily GDF11 injections can shrink heart muscle in both old and new mice. But this time they note another observation: The mice also lost weight. ?We don?t have much insight into that right now, but we?re looking into it,? Wagers says. She says the findings suggest that as with other hormones, GDF11 may have ?a therapeutic window? for beneficial effects?too much may cause harm.

Houser says he agrees that one of the Novartis team?s assays for GDF11 was probably detecting immunoglobulin. But Houser notes that the group also used a different assay to detect GDF11 and that isn?t challenged by the new paper. (David Glass makes the same point.) Sorting out what role GDF11 may play in aging is important, Houser adds. ?I’m going to be 65 in a couple months. I’d love to have something that improves my heart, brain, and muscle function,? Houser says. ?I think the field is going to figure this out and this is another piece of the puzzle.?