Dr Bryant Villeponteau the formulator of Stem Cell 100 and other Life Code nutraceuticals was recently interviewed by Dr Mercola who owns the largest health web site on the internet. Dr. Villeponteau is also the author of Decoding Longevity an new book which will be released during December. He is a leading researcher in novel anti-aging therapies involving stem cells an area in which he has been a pioneer for over three decades.
Stem cell technology could have a dramatic influence on our ability to live longer and replace some of our failing parts, which is the inevitable result of the aging process. With an interest in aging and longevity, Dr. Villeponteau started out by studying developmental biology. “If we could understand development, we could understand aging,” he says. Later, his interest turned more toward the gene regulation aspects. While working as a professor at the University of Michigan at the Institute of Gerontology, he received, and accepted, a job offer from Geron Corporation—a Bay Area startup, in the early ‘90s.
“They were working on telomerase, which I was pretty excited about at the time. I joined them when they first started,” he says. “We had an all-out engagement there to clone human telomerase. It had been cloned in other animals but not in humans or mammals.”
If you were to unravel the tip of the chromosome, a telomere is about 15,000 bases long at the moment of conception in the womb. Immediately after conception, your cells begin to divide, and your telomeres begin to shorten each time the cell divides. Once your telomeres have been reduced to about 5,000 bases, you essentially die of old age.
“What you have to know about telomerase is that it’s only on in embryonic cells. In adult cells, it’s totally, for the most part, turned off, with the exception of adult stem cells,” Dr. Villeponteau explains. “Adult stem cells have some telomerase – not full and not like the embryonic stem cells, but they do have some telomerase activity.”
Most of the research currently being done, both in academia and industrial labs, revolves around either embryonic stem cells, or a second type called induced pluripotent stem cells (iPS). Dr. Villeponteau, on the other hand, believes adult stem cells are the easiest and most efficient way to achieve results.
That said, adult stem cells do have their drawbacks. While they’re your own cells, which eliminates the problem of immune-related issues, there’s just not enough of them. Especially as you get older, there are fewer and fewer adult stem cells, and they tend to become increasingly dysfunctional too. Yet another hurdle is that they don’t form the tissues that they need to form…
To solve such issues, Dr. Villeponteau has created a company with the technology and expertise to amplify your adult stem cells a million-fold or more, while still maintaining their ability to differentiate all the different cell types, and without causing the cells to age. Again, it is the adult stem cell’s ability to potentially cure, or at least ameliorate, many of our age-related diseases by regenerating tissue that makes this field so exciting.
Dr Villeponteau believes you can add many years, likely decades, to your life simply by eating right, exercising (which promotes the production of muscle stem cells, by the way) and living an otherwise clean and healthy lifestyle. Extreme life extension, on the other hand, is a different matter.
His book, Decoding Longevity, covers preventive strategies to prolong your life, mainly diet, exercise, and supplements. A portion of the book also covers future developments in the area of more radical life extension, such as stem cell technology.
If you would like to read the entire interview here is a link to the text version:
Now researchers have found a way not just to stop, but, reverse the aging process. The key is something called a telomere. We all have them. They are the tips or caps of your chromosomes. They are long and stable in young adults, but, as we age they become shorter, damaged and frayed. When they stop working we start aging and experience things like hearing and memory loss.
In a recent study published in the peer reviewed journal Nature scientists took mice that were prematurely aged to the equivalent of 80-year-old humans, added an enzyme and essentially turned their telomeres back on. After the treatment they were the physiological equivalent of young adults. You can see the before and after pictures in the videos above. Brain function improved, their fertility was restored it was a remarkable reversal of the aging process. In the top video the untreated mouse shows bad skin, gray hair and it is balding. The mouse with it’s telomeres switched back on has a dark coat color, the hair is restored and the coat has a nice healthy sheen to it. Even more dramatic is the change in brain size. Before treatment the aged mice had 75% of a normal size brain like a patient with severe Alzheimers. After the telomeres were reactivated the brain returned to normal size. As for humans while it is just one factor scientists say the longer the telomeres the better the chances for a more graceful aging.
The formal study Telomere dysfunction induces metabolic and mitochondrial compromise was published in Nature.
Additional information published by Harvard can be found in the following articles.
While scientists are not yet able to accomplish the same results in humans we believe we have developed a nutraceutical to help prolong youth and possibly extend life until age reversal therapy for humans becomes available.
New evidence that adult stem cells are critical to human aging has recently been published on a study done on a super-centenarian woman that lived to be 115 years. At death, her circulating stem cell pool had declined to just two active stem cells from stem cell counts that are typically more than a thousand in younger adults. Super-centenarians have survived all the normal diseases that kill 99.9% of us before 100 years of age, so it has been a mystery as to what actually kills these hardy individuals. This recent data suggest that stem cell decline may be the main contributor to aging. If so, stabilizing stem cells may be the best thing one can do to slow your rate of aging.
There are many theories of aging that have been proposed. For example, damage to cells and tissues from oxidative stress has been one of the most popular fundamental theories of aging for more than half a century. Yet antioxidant substances or genes that code antioxidant enzymes have proven largely ineffective in slowing aging when tested in model animals. Thus, interest by scientists has shifted to other hypotheses that might provide a better explanation for the slow declines in function with age.
Stem cells provide one such promising mechanism of aging. Of course, we all know that babies are young and vigorous, independent of the age of their parents. This is because adults have embryonic stem cells that can generate young new cells needed to form a complete young baby. Indeed, these embryonic stem cells are the product of continuously evolving stem cell populations that go back to the beginning of life on earth over 3.5 billion years ago!
In adults, the mostly immortal embryonic stem cells give rise to mortal adult stem cells in all the tissues of the body. These adult stem cells can regenerate your cells and tissues as they wear out and need replacement. Unfortunate, adult stem cells also age, which leads to fewer cells and/or loss of function in cell replacement. As functional stem cells decline, skin and organs decline with age.
The somatic mutation burden in healthy white blood cells (WBCs) is not well known. Based on deep whole-genome sequencing, we estimate that approximately 450 somatic mutations accumulated in the nonrepetitive genome within the healthy blood compartment of a 115-yr-old woman. The detected mutations appear to have been harmless passenger mutations: They were enriched in noncoding, AT-rich regions that are not evolutionarily conserved, and they were depleted for genomic elements where mutations might have favorable or adverse effects on cellular fitness, such as regions with actively transcribed genes. The distribution of variant allele frequencies of these mutations suggests that the majority of the peripheral white blood cells were offspring of two related hematopoietic stem cell (HSC) clones. Moreover, telomere lengths of the WBCs were significantly shorter than telomere lengths from other tissues. Together, this suggests that the finite lifespan of HSCs, rather than somatic mutation effects, may lead to hematopoietic clonal evolution at extreme ages.
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:
11. Sweet bell peppers
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
6. Frozen sweet peas
11. Honeydew melon
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.”
Neil Charness, professor of psychology and a leading authority on aging and cognition, teamed up with Wally Boot, associate professor of psychology, and graduate student Dustin Souders to test the theory that brain games help preserve cognitive function.
Charness, who’s also the director of FSU’s Institute for Successful Longevity, said an increasing number of people believe brain training helps protect them against memory loss or cognitive disorders.
“Brain challenges like crossword games are a popular approach, especially among baby boomers, as a way to try to protect cognition,” Charness said.
That popularity has turned the brain-training industry into a billion-dollar business. Brain games are available online and through mobile apps that typically sell for about $15 a month or $300 for lifetime memberships.
Be skeptical of ads declaring you can rev up your brain’s performance by challenging it with products from the growing brain-training industry.
Science does not support many of the claims.
That’s according to a new study published in the science journal Frontiers in Aging Neuroscience from a team of Florida State University researchers.
“Our findings and previous studies confirm there’s very little evidence these types of games can improve your life in a meaningful way,” said Boot, an expert on age-related cognitive decline.
Advertising for this rapidly growing business sector has sometimes used inflated claims. The Federal Trade Commission fined one brain-training company $50 million for false advertising, which was later lowered to $2 million.
“More companies are beginning to be fined for these types of inflated claims and that’s a good thing,” Boot said. “These exaggerated claims are not consistent with the conclusions of our latest study.”
The FSU team’s study focused on whether brain games could boost the “working memory” needed for a variety of tasks. In their study, they set up one group of people to play a specially designed brain-training video game called “Mind Frontiers,” while another group of players performed crossword games or number puzzles.
All players were given lots of information they needed to juggle to solve problems. Researchers tested whether the games enhanced players’ working memory and consequently improved other mental abilities, such as reasoning, memory and processing speed.
That’s the theory behind many brain games: If you improve overall working memory, which is fundamental to so much of what we do every day, then you can enhance performance in many areas of your life.
The team examined whether improving working memory would translate to better performance on other tasks or as the researchers called it: “far transfer.”
In short, no.
“It’s possible to train people to become very good at tasks that you would normally consider general working memory tasks: memorizing 70, 80, even 100 digits,” Charness said. “But these skills tend to be very specific and not show a lot of transfer. The thing that seniors in particular should be concerned about is, if I can get very good at crossword puzzles, is that going to help me remember where my keys are? And the answer is probably no.”
Charness has spent much of his career the past 45 years trying to wrap his brain around the way the mind functions and how it ages. With the senior population continuing to grow 45 million Americans are 65 or older Charness understands their concerns about preserving brain function and remaining independent.
“People have real concerns about loss of cognition and loss of memory as they age, so they do all kinds of things to try to stave off cognitive decline,” Charness said.
Charness noted that other research finds aerobic exercise, rather than mental exercise, is great for your brain. Physical exercise can actually cause beneficial structural changes in the brain and boost its function. He predicts “exer-gaming,” which combines exercise with brain games, will increase in popularity in the 21st century.
“I wouldn’t come away from our article totally discouraged,” Charness said. “It’s another piece of the puzzle that we’re all trying to assemble. It’s discouraging in the sense that we can’t find far transfer and that seems to be a fairly consistent finding in research. But if your real goal is to improve cognitive function and brain games are not helping, then maybe you are better off getting aerobic exercise rather than sitting in front of the computer playing these games.”
Reference: Souders Dustin J., Boot Walter R., Blocker Kenneth, Vitale Thomas, Roque Nelson A., Charness Neil. Evidence for Narrow Transfer after Short-Term Cognitive Training in Older Adults. Frontiers in Aging Neuroscience, 2017; DOI: 10.3389/fnagi.2017.00041
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
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/
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.
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
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.