lroot on April 25th, 2017

Woman Lifting Dumbbells

A study led by the University of Sydney in Australia has found that gradually increasing muscle strength through activities such as weightlifting improves cognitive function.

The study was conducted in collaboration with the Centre for Healthy Brain Aging at the University of New South Wales and the University of Adelaide.

The results have been published in the Journal of American Geriatrics.

The trial involved a Study of Mental and Resistance Training carried out on patients with mild cognitive impairment between 55-68 years old. Patients with the condition have a higher risk of developing dementia and Alzheimer’s disease.

The findings are particularly significant given the high incidence of dementia and Alzheimer’s disease among the aging population. According to the 2016 World Alzheimer Report, 47 million people worldwide have dementia and this number is expected to triple by 2050.

In the United States, the figure predicted for people with Alzheimer’s disease in 2050 is 13.8 million.

Due to the high cost of care for patients with dementia, the World Alzheimer Report recommends moving beyond specialist care. The report suggests a holistic approach that focuses on improving the quality of life for people living with the condition.

Seen in this context, a link between physical training and improving brain function might be a step in the right direction.

How a disciplined weightlifting schedule can improve cognition

The trial looked at progressive resistance training such as weightlifting and the functioning of the brain.

The study examined 100 older adults living with mild cognitive impairment which refers to older patients who have cognitive difficulties that are noticeable but not significant enough to interfere with their daily activities.

Eighty percent of patients diagnosed with mild cognitive impairment develop Alzheimer’s disease after approximately 6 years.

For the trial, patients with mild cognitive impairment were divided into four groups and assigned a range of activities. These included a combination of resistance exercise including weightlifting and placebo resistance in the form of seated stretching. Activities also included computerized cognitive training and its placebo equivalent.

The cognitive training and placebo activities did not yield cognitive improvements.

However, the study did demonstrate a proportional relation between improvement in brain function and improvement in muscle strength.

Previous studies have shown a positive link between physical exercise and cognitive function, but the trial led by Dr. Mavros provides further information on the type, quality, and frequency of exercise needed to get the full cognitive benefits.

In the trial, participants did weightlifting sessions twice a week for 6 months, working to at least 80 percent of their peak strength. The weights were gradually increased as participants got stronger, all the while maintaining their peak strength at 80 percent.

“The more we can get people doing resistance training like weightlifting, the more likely we are to have a healthier aging population,” says Dr. Mavros. “The key, however, is to make sure you are doing it frequently, at least twice a week, and at a high intensity so that you are maximizing your strength gains. This will give you the maximum benefit for your brain.”

This is also the first time a study has shown a clear causal link between increasing muscle strength and improving brain function in patients over 55 years old who have MCI.

It has been suggested that exercise indirectly helps prevent the onset of Alzheimer’s disease and lowers the risk of cognitive impairment. Exercise helps with physiological processes such as glucoregulation and cardiovascular health. When these are sub-optimal, they increase the risk of cognitive impairment and Alzheimer’s disease.

Exercise also improves other cognitive processes, such as selective attention, planning, organizing, and multitasking.

Some studies have also suggested a connection between an increase in the size of certain brain areas and exercise training.

With age, the hippocampus is known to reduce in size, which leads to cognitive impairment. However, aerobic exercise has shown an increase in the size of the anterior hippocampus by 2 percent, which can improve spatial memory.

Earlier this year, a team of researchers that included Dr. Mavros released a similar test where they noticed cognitive improvement after weightlifting.

Using functional magnetic resonance, they analyzed changes in the brain after 6 months of progressive resistance training and computerized cognitive training in older adults. They found that progressive resistance training such as weightlifting “significantly improved global cognition.”

Authors of this study pointed out that it remains unclear whether physical training in itself stops the degenerative effects of old age, or whether they boost some other mechanisms that support cognition.

Although muscle strength seems to be clearly connected with cognitive impairment, the mechanism behind it is still not entirely evident.

In the future, Mavros and team hope to uncover it by connecting the increases in brain size to muscle strength and cognitive improvement.

lroot on April 17th, 2017

Adult Stem Cells

Wellcome Trust Sanger Institute scientists and their collaborators at the University of Cambridge have created a new technique that simplifies the production of human brain and muscle cells allowing millions of functional cells to be generated in just a few days. The results published in Stem Cell Reports open the door to producing a diversity of new cell types that could not be made before.

Human pluripotent stem cells offer the ability to create any tissue, including those which are typically hard to access, such as brain cells.

In a human, it takes nine to twelve months for a single brain cell to develop fully. To create human brain cells, including grey matter (neurons) and white matter (oligodendrocytes) from an induced pluripotent stem cell, it can take between three and twenty weeks using current methods. However, these methods are complex and time-consuming, often producing a mixed population of cells.

The new platform technology, OPTi-OX, optimises the way of switching on genes in human stem cells. Scientists applied OPTi-OX to the production of millions of nearly identical cells in a matter of days. In addition to the neurons, oligodendrocytes, and muscle cells the scientists created in the study, OPTi-OX holds the possibility of generating any cell type at unprecedented purities, in this short timeframe.

To produce the neurons, oligodendrocytes, and muscle cells, scientists altered the DNA in the stem cells. By switching on carefully selected genes, the team “reprogrammed” the stem cells and created a large and nearly pure population of identical cells. The ability to produce as many cells as desired combined with the speed of the development gives an advantage over other methods. The new method opens the door to drug discovery, and potentially therapeutic applications in which large amounts of cells are needed.

An author of the study, Dr Ludovic Vallier from the Wellcome Trust Sanger Institute said: “What is really exciting is we only needed to change a few ingredients — transcription factors — to produce the exact cells we wanted in less than a week. We over-expressed factors that make stem cells directly convert into the desired cells, thereby bypassing development and shortening the process to just a few days.”

OPTi-OX has applications in various projects, including the possibility to generate new cell types which may be uncovered by the Human Cell Atlas. The ability to produce human cells so quickly means the new method will facilitate more research.

Joint first author, Daniel Ortmann from the University of Cambridge, said: “When we receive a wealth of new information on the discovery of new cells from large scale projects, like the Human Cell Atlas, it means we’ll be able to apply this method to produce any cell type in the body, but in a dish.”

Mark Kotter, lead author and Clinician from the University of Cambridge, said: “Neurons produced in this study are already being used to understand brain development and function. This method opens the doors to producing all sorts of hard-to-access cells and tissues so we can better our understanding of diseases and the response of these tissues to newly developed therapeutics.”

Reference: Matthias Pawlowski, Daniel Ortmann, Alessandro Bertero, Joana M. Tavares, Roger A. Pedersen, Ludovic Vallier, Mark R.N. Kotter. Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes. Stem Cell Reports, 2017; DOI: 10.1016/j.stemcr.2017.02.016

fruit and vegetables

More and more Americans are demanding food free of synthetic chemicals. But tests by the U.S. Department of Agriculture found that nearly 70 percent of samples of 48 types of conventionally grown produce were contaminated with pesticide residues.

The USDA found a total of 178 different pesticides and pesticide breakdown products on the thousands of produce samples it analyzed. The pesticides persisted on fruits and vegetables even when they were washed and, in some cases, peeled.

But there are stark differences in the number and amount of pesticides on various types of produce. The Environmental Working Group’s annual Shopper’s Guide to Pesticides in Produce lists the 12 fruits and vegetables with the most pesticide residues, and the 15, for which few, if any, residues were detected.

When buying organic produce is not an option, use the Shopper’s Guide to choose foods lower in pesticide residues. With the Shopper’s Guide, you can have the health benefits of a diet rich in fruits and vegetables while limiting your exposure to pesticides.

This year the list of produce with the highest loads of pesticide residues includes, in order starting with the highest contamination:

1. Strawberries
2. Spinach
3. Nectarines
4. Apples
5. Peaches
6. Celery
7. Grapes
8. Pears
9. Cherries
10. Tomatoes
11. Sweet bell peppers
12. Potatoes

Each of these foods tested positive for a number of different pesticide residues and contained higher concentrations of pesticides than other produce. More than 98 percent of samples of strawberries, spinach, peaches, nectarines, cherries and apples tested positive for residue of at least one pesticide. A single sample of strawberries showed 20 different pesticides. Spinach samples had, on average, twice as much pesticide residue by weight than any other crop.

The Environmental Working Group’s list of produce least likely to contain pesticide residues included:

1. Sweet Corn
2. Avocados
3. Pineapples
4. Cabbage
5. Onions
6. Frozen sweet peas
7. Papayas
8. Asparagus
9. Mangoes
10. Eggplant
11. Honeydew melon
12. Kiwis
13. Cantaloupe
14. Cauliflower
15. Grapefruit

Relatively few pesticides were detected on these foods, and tests found low total concentrations of pesticide residues on them. Avocados and sweet corn were the cleanest with only 1 percent of the samples showing any detectable pesticides. More than 80 percent of pineapples, papayas, asparagus, onions and cabbage had no pesticide residues. No single fruit sample from the cleanest list tested positive for more than four types of pesticides. Multiple pesticide residues are extremely rare on these vegetables. Only 5 percent of had two or more pesticides.

Most processed foods typically contain one or more ingredient derived from genetically engineered crops, such as corn syrup and corn oil made from predominantly GMO starchy field corn. Yet GMO food is not often found in the produce section of American supermarkets. A small percentage of zucchini, yellow squash and sweet corn is genetically modified. Most Hawaiian papaya is GMO. Other varieties of GMO foods are currently being tested. The USDA may approve them in the future.

Because federal law does not require labeling of genetically engineered produce, people who want to avoid GMO crops can purchase organically grown sweet corn, papaya, zucchini and yellow squash. For processed foods, look for items that are certified organic.

People who eat organic produce eat fewer pesticides. A 2015 study by Cynthia Curl of the University of Washington found that people who report they “often or always” buy organic produce had significantly less organophosphate insecticides in their urine samples. This was true even though they reported eating 70 percent more servings of fruits and vegetables per day than adults reporting they “rarely or never” purchase organic produce. Several long-term observational studies have indicated that organophosphate insecticides may impair children’s brain development.

In 2012, the American Academy of Pediatrics issued an important report that said children have “unique susceptibilities to [pesticide residues’] potential toxicity.” The pediatricians’ organization cited research that linked pesticide exposures in early life to “pediatric cancers, decreased cognitive function, and behavioral problems.” It advised its members to urge parents to consult “reliable resources that provide information on the relative pesticide content of various fruits and vegetables.”

lroot on April 11th, 2017

Clock

Aging in humans (and animals) can be seen as either an inevitable process of wear and tear or as an inherent biological program by which the lifespan of each species is more or less predetermined. Recent research has shown that DNA methylation, an epigenetic modification which alters how DNA is read and expressed without altering the underlying sequence, can show age related changes. A sub-set of these modifications are so accurate that chronological age in humans can be predicted +/- 3.6 years from any tissue or fluid in the body (Horvath S. 2013). This is by far the best biomarker of age available and is referred to as the epigenetic clock. Interestingly, analysis of DNA methylation can also provide information on biological age, which is a measure of how well your body functions compared to your chronological age. For instance, people who are centenarians have a slower clock.

But, how does this epigenetic clock work? And is it possible to change the ticking rate? Researchers at the Babraham Institute and the European Bioinformatics Institute have now identified a mouse epigenetic aging clock. This work, published today in Genome Biology, shows that changes in DNA methylation at 329 sites in the genome are predictive of age in the mouse with an accuracy of +/- 3.3 weeks. Considering that humans live to approximately 85 years and mice to 3 years, the accuracy of the mouse and human clocks (better than 5%) are surprisingly similar.

Using the mouse model, researchers also showed that lifestyle interventions known to shorten lifespan sped up the clock. For example, removing the ovaries in female mice accelerates the clock, something that is also observed in early menopause in women. And interestingly a high fat diet which we know is detrimental to human health also accelerates the ageing clock. Remarkably, researchers were able to detect changes to the epigenetic clock as early as 9 weeks of age, bearing in mind that the lifespan of a mouse can easily be more than 3 years, this represents a massive reduction in both time and cost which the researchers believe will accelerate future ageing discoveries.

Tom Stubbs, PhD Student in the Reik group at the Babraham Institute and lead author of the paper, said: “The identification of a human epigenetic ageing clock has been a major breakthrough in the ageing field. However, with this finding came a number of questions about its conservation, its mechanism and its function. Our discovery of a mouse epigenetic ageing clock is exciting because it suggests that this epigenetic clock may be a fundamental and conserved feature of mammalian ageing. Importantly, we have shown that we can detect changes to the ticking rate in response to changes, such as diet, therefore in the future we will be able to determine the mechanism and function of this epigenetic clock and use it to improve human health.”

Dr. Marc Jan Bonder, postdoctoral researcher at the European Bioinformatics Institute, adds: “Dissecting the mechanism of this mouse epigenetic ageing clock will yield valuable insights into the aging process and how it can be manipulated in a human setting to improve health span.”

With further study, scientists will be able to understand the inner mechanistic workings of such a clock (for example using knowledge about enzymes that regulate DNA methylation in the genome) and change its ticking rate in the mouse model. This will reveal whether the clock is causally involved in aging, or whether it is a read-out of other underlying physiological processes. These studies will also suggest approaches to wind the aging clock back in order to rejuvenate tissues or even a whole organism.

Professor Wolf Reik, Head of the Epigenetics Programme at the Babraham Institute, said: “It is fascinating to imagine how such a clock could be built from molecular components we know a lot about (the DNA methylation machinery). We can then make subtle changes in these components and see if our mice live shorter, or more interestingly, longer.” Such studies may provide deeper mechanistic insights into the ageing process and whether lifespan in a species is in some way programmed.”

Reference: Thomas M. Stubbs, Marc Jan Bonder, Anne-Katrien Stark, Felix Krueger, Ferdinand von Meyenn, Oliver Stegle, Wolf Reik. Multi-tissue DNA methylation age predictor in mouse. Genome Biology, 2017; 18 (1) DOI: 10.1186/s13059-017-1203-5

lroot on April 3rd, 2017

Skin Stem Cells

When a person is severely burned it is a serious skin injury. Typically the treatment involves grafting a layer of skin from a healthy part of the body to the injured area. Once the grafted skin heals which can take some time there is usually very unsightly scarring which the person has to live with the rest of their life. If the scarring is on the face the disfigurement can cause major emotional problems. Also grafted skin often lacks flexibility which leads to pain, stiffness and other problems.

What if there was a way to isolate stem cells from healthy skin, process them and spray them on the burned or injured area. The stem cells would generate fresh new skin within days and without scarring or other problems associated with grafting. This might seem like one of those articles about a stem cell technology that is in the research and development stage with the prospect that it will be available for actual human treatment in 10 or 15 years, however it has already been successfully used to treat human burn patients in Europe. An actual example is shown in the before and after image. This treatment can also be used for cosmetic purposes such as replacing scar tissue with healthy new skin.

The CellMist™ Solution is a new invention that involves a liquid suspension containing a patient’s own regenerative skin stem cells. A small sample (as little as a square inch) of the patient’s skin is quickly processed to liberate the stem cells from surrounding tissue. The resulting product is referred to as the ‘CellMist™ Solution’ containing the patient’s stem cells. The CellMist™ Solution is placed in a device called the SkinGun™ for spray application onto the patient’s wound.

The SkinGun™ sprays the cells onto wound sites to begin healing. Unlike conventional aerosol and pump systems, this next-generation fluid sprayer does not expose fragile cells to strong forces that can tear them apart. Instead the SkinGun™ gently delivers the CellMist™ Solution directly to the wound site using a positive-pressure air stream.

RenovaCare, a developer of novel medical grade liquid spray devices and patented CellMist™ and SkinGun™ technologies*, announced favorable outcomes from laboratory studies conducted by Berlin-Brandenburg Center for Regenerative Therapies (BCRT), a translational research center at Charité Universitätsmedizin Berlin, one of the world’s largest university hospitals.

The goal was to work towards the use of CellMist™ and SkinGun™ technologies to quickly isolate a patient’s own stem cells and gently spray them onto burns and wounds for rapid self-healing. The results of a new study provide pre-clinical support for first isolating keratinocytes from skin samples, and subsequently achieving even and gentle spray application without harming these powerful yet delicate cells.

Charité scientists presented their findings from in vitro studies at the EPUAP Focus Meeting 2016 in Berlin, Germany. Data demonstrated that human skin stem cells sprayed with the company’s patented SkinGun™ device maintained 97.3% viability. Cell viability is essential to regenerating skin for burns, wounds, and cosmetic applications. Cell growth was comparable to pipetting, the industry’s widely accepted ‘gold-standard’ for the deposition of cells.

The results show that the described method consistently allows isolating keratinocytes with characteristics suitable for therapeutic applications. This indicates that use of the SkinGun™ for spray application of keratinocytes may allow for even distribution of cells with no impairment of cell viability or cell growth when evaluated in vitro, in contrast to those evaluations with conventionally seeded cells, according to study authors, Dr. Christa Johnen, Nadja Strahl, and Dr. Katrin Zeilinger.

Among specific aims of the study, was evaluation of several factors important to the regeneration of human skin, including cell yield, viability, metabolic activity, and cell growth. Positive results were reported from experiments related to each of these investigations. After spraying skin stem cells using the RenovaCare SkinGun™, investigators recorded favorable metabolic activity from measurements of glucose consumption and lactate release. Cell morphology was evaluated by microscopic observation, and cell integrity was determined by LDH release.

The study was funded by RenovaCare, Inc. Tissue samples for skin cell isolation were obtained from surgical treatments with approval of the Charité ethical committee.

*RenovaCare products are currently in development. They are not available for sale in the United States. There is no assurance that the company’s planned or filed submissions to the U.S. Food and Drug Administration, if any, will be accepted or cleared by the FDA.

RenovaCare, Inc. is developing first-of-their-kind autologous (self-donated) stem cell therapies for the regeneration of human organs, and novel medical grade liquid sprayer devices.

In addition to its liquid spray devices for wound irrigation, the company’s pipeline products under development target the body’s largest organ, the skin. The RenovaCare CellMist™ System will use the patented SkinGun™ to spray a liquid suspension of a patient’s stem cells – the CellMist™ Solution – onto wounds. RenovaCare is developing its CellMist™ System as a promising new alternative for patients suffering from burns, chronic and acute wounds, and scars. In the U.S. alone, this $45 billion market is greater than the spending on high-blood pressure management, cholesterol treatments, and back pain therapeutics.

A video of a patient who was treated for severe burns can be viewed at http://renovacareinc.com/2016/07/burn-recovery-video-state-trooper/

lroot on March 28th, 2017

Astaxanthin

Life Code supplements are formulated to improve the quality of life and increase lifespan. An important study has just been released showing that one of the many ingredients (Astaxathin) in our nutraceutical supplement EpiMax upregulates the FOX03 longevity gene. We use a natural Astaxathin derived from algae which includes other lipid soluble anti-oxidants and synergistic co-factors.

The University of Hawaii John A. Burns School of Medicine (“JABSOM”) and Cardax, Inc., a Honolulu based life sciences company, jointly announced the results of the animal study evaluating the effectiveness of Astaxathin and demonstrating that it holds promise in anti-aging therapy.

“All of us have the FOXO3 gene, which protects against aging in humans,” said Dr. Bradley Willcox, MD, Professor and Director of Research at the Department of Geriatric Medicine, JABSOM, and Principal Investigator of the National Institutes of Health-funded Kuakini Hawaii Lifespan and Healthspan Studies. “But about one in three persons carry a version of the FOXO3 gene that is associated with longevity. By activating the FOXO3 gene common in all humans, we can make it act like the “longevity” version. Through this research, we have shown that Astaxanthin “activates” the FOXO3 gene,” said Willcox.

“This preliminary study was the first of its kind to test the potential of Astaxanthin to activate the FOXO3 gene in mammals,” said Dr. Richard Allsopp, PhD, Associate Professor, and researcher with the JABSOM Institute of Biogenesis Research.

In the study, mice were fed either normal food or food containing a low or high dose of the Astaxanthin compound CDX-085 which is a synthetically manufactured Astaxanthin. The animals that were fed the higher amount of the Astaxanthin compound experienced a significant increase in the activation of the FOXO3 gene in their heart tissue. Because only a limited amount of naturally produced Astaxathin is available a synthetic version has the advantage that unlimited quantities can be manufactured.

“We found a nearly 90% increase in the activation of the FOXO3 “Longevity Gene” in the mice fed the higher dose of the Astaxanthin compound CDX-085,” said Dr. Allsopp.

Astaxanthin is a naturally occurring compound found in seafood such as shrimp, lobster, and salmon, and is typically sourced from algae, krill, or synthesis. Multiple animal studies have demonstrated that Astaxanthin provides heart, liver, blood and other benefits.

Astaxanthin is the active ingredient in CDX-085, Cardax’s patented second generation compound. “This proprietary compound, like our first generation product ZanthoSyn, delivers Astaxanthin to the blood stream with superior absorption and purity, but in a more concentrated form, allowing higher doses per capsule and improved dosing convenience,” said Watumull. In animal study results published in peer-reviewed papers, CDX-085 statistically significantly lowered triglycerides by 72% as well as atherosclerosis and blood clots.

Researchers with the Kuakini Hawaii Lifespan Study, sponsored by the National Institutes of Health and Kuakini Medical Center, discovered that for those who have a certain gene (the FOXO3 “G” genotype) there is “extra protection” against the risk of death as you get older, compared to average persons. Using data from the Kuakini Hawaii Lifespan Study, a substudy of the 50-year Kuakini Honolulu Heart Program (Kuakini HHP), and the National Institute on Aging’s Health, Aging and Body Composition (Health ABC) study as a replication cohort, researchers found that people with this FOXO3 gene have an impressive 10% reduced risk of dying overall over a 17 year period. Data are based on a 17-year prospective cohort study of 3,584 older American men of Japanese ancestry from the Kuakini HHP cohort study and a 17-year prospective replication study of 1,595 white and 1,056 African-American elderly individuals from the Health ABC cohort.

lroot on March 22nd, 2017

Stem Cells

UC San Francisco scientists identified a previously unknown pool of blood making stem cells in the lungs capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted. Using video microscopy in the living mouse lung, the scientists have revealed that the lungs play this previously unrecognized role in blood production. As reported online March 22, 2017 in Nature, the researchers found that the lungs produced more than half of the platelets blood components required for the clotting that stanches bleeding in the mouse circulation.

“This finding definitely suggests a more sophisticated view of the lungs that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said pulmonologist Mark R. Looney, MD, a professor of medicine and of laboratory medicine at UCSF and the new paper’s senior author. “What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The findings could have major implications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

Mouse lungs produce more than 10 million platelets per hour, live imaging studies show

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-author Matthew F. Krummel, PhD, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said Emma Lefrançais, PhD, a postdoctoral researcher in Looney’s lab and co-first author on the new paper.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature estimated at 1 million per mouse lung.

Newly discovered blood stem cells in the lung can restore damaged bone marrow

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, also a postdoctoral researcher in the Looney lab and the paper’s other co-first author. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation — much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” said Looney, who is also an attending physician on UCSF’s pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation and lung biology. The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. “We’re seeing more and more that the stem cells that produce the blood don’t just live in one place but travel around through the blood stream. Perhaps ‘studying abroad’ in different organs is a normal part of stem cell education.”

Reference: 1.Emma Lefrançais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier, Beñat Mallavia, Fengchun Liu, David M. Sayah, Emily E. Thornton, Mark B. Headley, Tovo David, Shaun R. Coughlin, Matthew F. Krummel, Andrew D. Leavitt, Emmanuelle Passegué, Mark R. Looney. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, 2017; DOI: 10.1038/nature21706

Coconuts

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

Coconut oil was once considered a “bad fat” since it contains saturated fatty acids, however it has a different chemical structure than saturated fats from animals or those that are synthetically produced such as margarine and other hydrogenated oils. Natural sources of saturated fats are gaining appreciation as beneficial, particularly for the brain. Even saturated fats from animals are not necessarily bad. It is excessive arachidonic acid which is found in the fat of grain fed animals such as most beef that is best avoided. That is caused by their diet which is too high in omega-6 polyunsaturated fatty acids and lacking omega-3 fatty acids. Meat from 100% grass fed beef or buffalo contains less arachidonic acid and a healthy balance of the two types of polyunsaturated fats.

The new study evaluated the health effects of consuming extra virgin coconut oil, focusing on how it affects heart health and a range of measurements including body weight, size, and circumference.

The average age of the participants was 62.4 years, 70% were elderly individuals, and 63.2% were males. During the first phase which lasted three months, 136 enrollees were put on a standardized diet. From the third month onward, the 116 who completed the first phase were placed in two groups with 22 remaining on the diet while 92 were put on the diet with .43 ounces daily of extra virgin coconut oil, which is equivalent to about 1 Tablespoon.

The results of the 3 month study showed that relative to the standard diet, the coconut oil group saw a decrease in all six of the bodily parameters measured, including weight loss of 1.3 pounds and waist size reduction of almost an inch. Additional testing also showed improvements in cardiovascular health. Previous studies of coconut oil have shown many benefits including improved cognition and enhanced nutrient absorption.

One of the advantages of coconut oil is that it does not oxidize during cooking as is the case with most other oils. That is one of the reasons why hydrogenated oils were created. Unfortunately they contain dangerous trans fatty acids so are best avoided. Back in the 1980’s many doctors and dieticians thought that coconut oil was bad because of it’s saturated oil content. Since then dozens of studies have found the opposite to be true. Also demographic studies have typically shown better heart health in countries where coconuts are eaten regularly.

lroot on March 1st, 2017

Autophagy

A molecular key to aging of the blood and immune system has been discovered in new research conducted at UC San Francisco, raising hope that it may be possible to find a way to slow or reverse many of the effects of aging.

The key is a link between the health of a rare population of adult stem cells that arise early in development and are responsible for replenishing all blood cell types throughout a lifetime, and a newly identified role for autophagy, an important cellular cleanup and recycling process that was the focus of the 2016 Nobel Prize in Physiology or Medicine.

In their new study, published online March 1 in Nature, the UCSF team discovered that in addition to its normal role in cellular waste-processing, autophagy also is needed for the orderly maintenance of blood-forming hematopoietic stem cells (HSCs), the adult stem cells that give rise to red blood cells, which carry oxygen, and to platelets, as well as the entire immune system.

The researchers found that autophagy keeps HSCs in check by allowing metabolically active HSCs to return to a resting, quiescent state akin to hibernation. This is the default state of adult HSCs, allowing their maintenance for a lifetime.

According to Emmanuelle Passegué, PhD, the senior scientist for the study, “This is a previously unknown role for autophagy in stem cell biology.”

Failure to activate autophagy has profound impacts on the blood system, Passegué’s team found, leading to the unbalanced production of certain types of blood cells. Defective autophagy also diminished the ability of HSCs to regenerate the entire blood system when they were transplanted into irradiated mice, a procedure similar to bone marrow transplantation.

The researchers determined that 70 percent of HSCs from old mice were not undergoing autophagy, and these cells exhibited the dysfunctional features common among old HSCs. However, the 30 percent of old HSCs that did undergo autophagy looked and acted like HSCs from younger mice.

Passegué led the study while she was a professor of medicine with the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF. In January she became an Alumni Professor in the Department of Genetics & Development and the director of the Columbia Stem Cell Initiative at Columbia University Medical Center.

Scientists have identified many different tissue-specific stem cells, all of whose performance declines with age, Passegué said. Finding out how this occurs has been an active area of research, and a focus of her laboratory group in recent years.

In a large series of experiments and analyses, many conducted by the study’s first author, Theodore Ho, a UCSF graduate student, the scientists compared characteristics of HSCs from old mice with those of HSCs from younger mice that had been genetically programmed so that they could not undergo autophagy. They found that loss of autophagy in young mice was sufficient to drive many of the defects that arise naturally in the blood of old mice, including changes in the cellular appearance of HSCs and a disruption in the normal proportions of the various types of blood cells, characteristics of old age.

Previous research had shown that autophagy causes the formation of “sacs” within cells that can engulf and enzymatically digest molecules and even major cellular structures, including mitochondria, the cell’s biochemical power plants. But in the new study, the researchers found that genetically programmed loss of autophagy resulted in the accumulation of activated mitochondria with increased oxidative metabolism that triggered chemical modifications of DNA in HSCs.

These “epigenetic” DNA modifications altered the activities of genes in a way that changed the developmental fate of HSCs. They triggered disproportionate production of certain blood cells and reduced the ability of HSCs to regenerate the entire blood system when transplanted. This result was similar to what the researchers observed in the majority of old HSCs that failed to activate autophagy.

In contrast, the minority of old HSCs that still exhibited significant levels of autophagy were able to keep their mitochondria and metabolism in check, and could re-establish a healthy blood system following transplantation, similar to HSCs from young mice.

However, in a hopeful sign for potential future therapies to rejuvenate blood stem cells, the researchers succeeded in restoring autophagy to old HSCs by treating them with pharmacological agents in a lab dish.

“This discovery might provide an interesting therapeutic angle to use in re-activating autophagy in all of the old HSCs, to slow the aging of the blood system and to improve engraftment during bone marrow or HSC transplantation,” Passegué said. “It is our hope that the end point will be a way to really improve the fitness of stem cells and to use that capability to help the immune systems.”

Reference: Theodore T. Ho, Matthew R. Warr, Emmalee R. Adelman, Olivia M. Lansinger, Johanna Flach, Evgenia V. Verovskaya, Maria E. Figueroa & Emmanuelle Passegué; Autophagy maintains the metabolism and function of young and old stem cells, Nature (2017). DOI: 10.1038/nature21388

lroot on February 22nd, 2017

Stem Cells

Our blood stem cells generate around a thousand billion new blood cells every day. But the blood stem cells’ capacity to produce blood declines as we age. This leads to lowered immunity and other age related problems. Now for the first time, a research team at Lund University in Sweden has succeeded in rejuvenating blood stem cells that had become less functional in aging mice. The study is published in Nature Communications.

When we are young, our blood stem cells produce an even and well-balanced number of red and white blood cells according to need. As we age, however, the capacity of the blood stem cells to produce the number of blood cells we need declines.

“This type of age-related change can have major consequences as it can lead to an imbalance in stem cell production. For example, a reduced production of immune cells or excessive production of other types of cells” explains David Bryder, who headed the study at Lund University.

A fundamental question was whether blood stem cells age differently within a single individual or whether all blood stem cells are equally affected by advancing age. In an initial stage, it was therefore important to genetically mark old blood stem cells, to enable the identification and tracking of those most affected by age. In the next step, these traceable cells were reprogrammed to another type of stem cell known as iPS cells, which can generate all cells in an individual and not only blood cells. When the cells are reprogrammed, their identity is ?re-set”; when these reprogrammed iPS cells formed new blood stem cells, the researchers observed that the re-set had entailed a rejuvenation of the cells.

“We found that there was no difference in blood-generating capacity when we compared the reprogrammed blood stem cells with healthy blood stem cells from a young mouse. This is, as far as we know, the first time someone has directly succeeded in proving that it is possible to recreate the function of young stem cells from a functionally old cell?, says Martin Wahlestedt, the first author of the study.

The research team’s studies have also thereby shown that many age-related changes in the blood system cannot be explained by mutations in the cells’ DNA. If the changes depended on permanent damage at the DNA level, the damage would still be present after the re-set. Instead, epigenetic changes appear to underlie the decline in function associated with advancing age.

“Our findings justify further research to improve the function of human blood stem cells” concludes David Bryder.

Reference: Martin Wahlestedt, Eva Erlandsson, Trine Kristiansen, Rong Lu, Cord Brakebusch, Irving L. Weissman, Joan Yuan, Javier Martin-Gonzalez, David Bryder. Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. Nature Communications, 2017; 8: 14533 DOI: 10.1038/ncomms14533