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 September 18th, 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 September 15th, 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.

Adult Stem Cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Ketogenic Foods

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

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

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

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

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

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

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

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

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

lroot on September 1st, 2017

fruit and vegetables

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

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

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

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

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

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

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

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

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

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

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

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

lroot on August 14th, 2017

Aerobic Exercise

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

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

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

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

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

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

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

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

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

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

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

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

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

lroot on August 11th, 2017

Sun

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

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

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

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

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

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

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

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

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

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

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

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

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

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

lroot on August 7th, 2017

Nonochip

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

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

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

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

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

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

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

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

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

lroot on August 2nd, 2017

Brain Training

Like much of the rest of the body, the brain loses flexibility with age, impacting the ability to learn, remember, and adapt. Now, scientists at University of Utah Health report they can rejuvenate the plasticity of the mouse brain, specifically in the visual cortex, increasing its ability to change in response to experience. Manipulating a single gene triggers the shift, revealing it as a potential target for new treatments that could recover the brain’s youthful potential. The research was published online in the Proceedings of the National Academy of Sciences (PNAS) on August 8.

“It’s exciting because it suggests that by just manipulating one gene in adult brains, we can boost brain plasticity,” says lead investigator Jason Shepherd, Ph.D., Associate Professor of Neurobiology and Anatomy at University of Utah Health.

“This has implications for potentially reducing normal cognitive decline with aging, or boosting recovery from brain injury after stroke or traumatic brain injury,” he says. Additional research will need to be done to determine whether plasticity in humans and mice is regulated in the same way.

The dramatic way in which the brain changes over time has long captured the imagination of scientists. A “critical window” of brain plasticity explains why certain eye conditions such as lazy eye can be corrected during early childhood but not later in life. The phenomenon has raised the questions: What ordinarily keeps the window open? And, once it’s shut, can plasticity be restored?

Earlier work that Shepherd carried out in collaboration with Mark Bear, Ph.D., a professor at the Massachusetts Institute of Technology and co-author of the current study, showed that the critical window never opens in mice lacking a gene called Arc. Temporarily closing a single eye of a young mouse for a few days deprives the visual cortex of normal input, and the neurons’ electrophysiological response to visual experience changes. By contrast, young mice without Arc cannot adapt to the new experience in the same way.

“Given our previous studies, we wondered whether Arc is essential for controlling the critical period of plasticity during normal brain development,” says Shepherd.

If there is no visual plasticity without Arc, the thinking goes, then perhaps the gene plays a role in keeping the “critical window” open.

In support of the idea, the new investigation finds that in the mouse visual cortex, Arc rises and falls in parallel with visual plasticity. The two peak in teen mice and fall sharply by middle-age, suggesting they are linked.

The researchers probed the connection further in two more ways. First, in collaboration with co-author Harohiko Bito, Ph.D., a professor at the University of Tokyo, they tested mice that have a strong supply of Arc throughout life. At middle-age, these mice responded to visual deprivation as robustly as their juvenile counterparts. By prolonging Arc’s availability, the window of plasticity remained open for longer.

Manipulating Arc is not the first treatment to prolong plasticity. Chronically treating mice with an antidepressant, fluoxetine, and raising rodents in a stimulating environment with toys and plenty of social interaction, are among other paradigms that do the same.

But the second set of experiments raised the bar higher. Viruses were used to deliver Arc to middle age mice, after the critical window had closed. Following the intervention, these older mice responded to visual deprivation as a youngster woulds. In this case even though the window had already shut, Arc enabled it to open once again.

“It was incredible to see that in adult mice, who have gone through normal development and aging, simply overexpressing Arc with a virus restored plasticity,” says co-first author Kyle Jenks, a graduate student in Shepherd’s lab.

The prevailing notion of how plasticity declines is that as the brain develops, inhibitory neurons mature and become stronger. Shepherd explains that he believes their findings add a new dimension for how critical periods of learning are regulated.

“Increased inhibition in the brain makes it harder to express activity-dependent genes, like Arc, in response to experience or learning,” he says. “And that leads to decreased brain plasticity.”

Normally, Arc is rapidly activated in response to stimuli and is involved in shuttling neurotransmitter receptors out of synapses that neurons use to communicate with one another. Additional research will need to be done to understand precisely how manipulating Arc boosts plasticity.

Whether Arc is involved in regulating the plasticity of other neurological functions mediated by other brain structures, like learning, memory, or repair, remains to be tested but will be examined in the future, says Shepherd.

Reference: Kyle R. Jenks, Taekeun Kim, Elissa D. Pastuzyn, Hiroyuki Okuno, Andrew V. Taibi, Haruhiko Bito, Mark F. Bear, and Jason D. Shepherd. Arc restores juvenile plasticity in adult mouse visual cortex. Proceedings of the National Academy of Sciences, August 2017 DOI: 10.1073/pnas.1700866114