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:

Transcript of Interview With Dr. Bryant Villeponteau by Dr. Joseph Mercola

lroot on May 17th, 2017

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.

Scientists Find Root Molecular Cause of Declining Health in the Old

Decoding Immortality – Smithsonian Channel Video about the Discovery of Telomerase

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.

lroot on May 12th, 2017

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.

Blood from world’s oldest woman suggests life limit

Time Magazine: Long-Life Secrets From The 115-Year-Old Woman

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

Abstract
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.

Stem Cells

The emergency call issued by the American Red Cross earlier this year was of a sort all too common: Donations of platelets were needed, and desperately. But a new discovery from the University of Virginia School of Medicine may be the key to stopping shortages of these vital blood-clotting cells.

The UVA researchers have identified a “master switch” that they may be able to manipulate to overcome the obstacles that have prevented doctors from producing platelets in large quantities outside the body. “The platelet supply is limited and the demand is growing,” said researcher Adam Goldfarb, MD, of UVA’s Department of Pathology. “The quantities we can produce outside the body are very, very small, and the inability to scale up right now is a major roadblock. We think that our understanding of this pathway is actually a critical step toward fixing that problem.”

Scientists also may be able to use this master switch to battle neonatal thrombocytopenia, a condition that complicates the care of babies who are already at great risk. “It turns out in premature infants and newborns that [the platelet] reserve is compromised. They are less capable of responding to distress and the demand for increased platelet production,” Goldfarb said. “A goodly percentage of those babies, these tiny little babies, require platelet transfusions to keep their platelets up.”

The switch discovered by Goldfarb’s team controls whether the bone marrow produces cells called megakaryocytes of the type seen in adults or of the sort found in infants. This is important because the adult and infantile versions have very different specialties: Adult megakaryocytes are great at making platelets. Lots and lots of them. Infantile megakaryocytes, on the other hand, are much smaller cells, and they concentrate on dividing to produce more megakaryocytes.

The ability to toggle between the two could be a huge asset for doctors. Now, doctors cannot produce large quantities of platelets in the lab and instead must rely on platelet donations for patients. The new finding, however, may help change that. “It’s thought that in our bodies every single megakaryocyte produces like a thousand platelets, and when you do it in culture [outside the body] it’s like 10,” he said. “We think the pathway we’re studying enhances the efficiency of platelet release, and this pathway, we think, could be manipulated in both directions: to suppress the pathway to promote the growth [of megakaryocytes] and then to activate the pathway at some point to enhance the efficiency of platelet release.”

For example, babies might be given a drug that would prompt their bodies to make more platelets. Researcher Kamal Elagib, MBBS, PhD, noted that the research team already has identified compounds that can flip the switch in the lab, but that those compounds likely aren’t the best option for treatment: “Those inhibitors have multiple effects, so there would be side effects,” he said.

The researchers, however, have already identified other drugs that look much more promising. “Our future efforts that Kamal is working on now are to identify better, cleaner, more effective approaches at flipping this switch,” Goldfarb said. “Understanding this process could really enhance the future approaches towards treating patients with low platelet counts.”

Reference: Kamaleldin E. Elagib, Chih-Huan Lu, Goar Mosoyan, Shadi Khalil, Ewelina Zasadzi?ska, Daniel R. Foltz, Peter Balogh, Alejandro A. Gru, Deborah A. Fuchs, Lisa M. Rimsza, Els Verhoeyen, Miriam Sansó, Robert P. Fisher, Camelia Iancu-Rubin, Adam N. Goldfarb. Neonatal expression of RNA-binding protein IGF2BP3 regulates the human fetal-adult megakaryocyte transition. Journal of Clinical Investigation, 2017; DOI: 10.1172/JCI88936

lroot on April 28th, 2017

heart

Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists. Now, Johns Hopkins researchers report success in creating them in the laboratory by implanting stem cells taken from a healthy adult or one with a type of heart disease into newborn rat hearts.

The researchers say the host animal hearts provide the biological signals and chemistry needed by the implanted immature heart muscle cells to progress and overcome the developmental blockade that traditionally stops their growth in lab culture dishes or flasks.

In a summary of the work published Jan. 10 in Cell Reports, the researchers say their method should help advance studies of how heart disease develops, along with the development of new diagnostic tools and stem cell treatments.

“Our concept of using a live animal host to enable maturation of cardiomyocytes can be expanded to other areas of stem cell research and really opens up a new avenue to getting stem cells to mature,” says Chulan Kwon, Ph.D., associate professor of medicine and member of the Johns Hopkins University School of Medicine’s Institute for Cell Engineering, who led the study.

According to Kwon, cell biologists have been historically unable to induce heart muscle cells to get past the point in development characteristic of newborns, even when they let them mature in dishes for a year.

Those neonatal heart cells, Kwon explains, are smaller and rounder than mature adult heart cells and generate very low pumping force. As a result, he adds, they aren’t the best model for heart muscle diseases, nor do they accurately mimic the biology and chemistry of adult heart tissue.

Kwon’s group recently showed that cells kept and grown in lab dishes weren’t turning on the proper genes needed to let the cells transition to maturity, a phenomenon they attributed to the artificial conditions of growing cells in a dish. But they also found that those genes were similar to those activated, or turned on, in the hearts of newborn rats.

In their initial experiments designed to overcome the developmental roadblock, the researchers first created a cell line of immature heart cells taken from mouse embryonic stem cells. They next tagged these cells with a fluorescent protein and injected about 200,000 of the cells into the ventricle or lower heart chamber of newborn nude rats — rats with deficient immune systems that wouldn’t attack and reject the newly introduced cells.

After about a week, Kwon reports, the fluorescent cells were still rounded and immature-looking. After a month, however, the cells looked like adult heart muscle cells — elongated with striped patterns.

When the researchers compared 312 genes in the individual mouse cells grown in the rat hearts to the genes found in both immature heart cells and adult heart muscle cells, they found the cells grown in the rat hearts had more in common with genetics of adult heart muscle cells.

The investigators confirmed that the new heart-grown cells could contract or beat like normal adult heart muscle cells using a type of optical microscopy.

In the next set of proof-of-concept experiments, Kwon’s team worked with human adult skin cells from a healthy human donor that were chemically converted back into a stem cell-like state known as induced pluripotent stem cells. A month after these cells were implanted into newborn rat hearts, the healthy human donor cells appeared rod-shaped and mature.

Kwon cautions that clinical use of these lab-grown cells is years away. But, he says, “The hope is that our work advances precision medicine by giving us the ability to make adult cardiomyocytes from any patient’s own stem cells.” Having that capability, he says, means having a way to test each patient for old and new drug sensitivities and value, and to have a scalable process to create large cell sources for heart regeneration.”

Reference: 1.Gun-Sik Cho, Dong I. Lee, Emmanouil Tampakakis, Sean Murphy, Peter Andersen, Hideki Uosaki, Stephen Chelko, Khalid Chakir, Ingie Hong, Kinya Seo, Huei-Sheng Vincent Chen, Xiongwen Chen, Cristina Basso, Steven R. Houser, Gordon F. Tomaselli, Brian O’Rourke, Daniel P. Judge, David A. Kass, Chulan Kwon. Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy. Cell Reports, 2017; 18 (2): 571 DOI: 10.1016/j.celrep.2016.12.040

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/