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 July 5th, 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 July 3rd, 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

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

Whether using embryonic or adult stem cells, coercing these master cells to convert to the desired target cell and reproduce flawlessly is difficult. Now an international team of researchers has a two-part system that can convert the cells to the targets and then remove the remnants of that conversion, leaving only the desired DNA behind to duplicate.

“One difficulty with human pluripotent stem cells is that you can’t use them directly,” said Xiaojun Lian, assistant professor of biomechanical engineering, biology and a member of the Huck Institutes of the Life Sciences, Penn State. They need to be the right type of differentiated cells for each tissue in the body.

Normally, pluripotent stem cells induced from both adult and embryonic cells receive a chemical signal to change from a stem cell to a functional cell. Pluripotent stem cells can change to any cell in the human body. However, this natural cell change is part of a complex series of triggers controlled by DNA. Researchers have in the past inserted DNA into the pluripotent cells to convert them, but remnants of the inserted DNA remain.

In this current work, published in a recent issue of Scientific Reports, the researchers are not incorporating a piece of DNA that will tell the cells to convert, but DNA that will make the cell glow green when illuminated by a blue light. This marker allows the researchers to see that the DNA plasmid is incorporated into the cell, and that it is completely gone upon removal. A plasmid is a circular piece of DNA that contains functional DNA fragments that control gene expression in cells.

“We wanted to explore the limits for turning the conversion on and off and to have the ability to control the level of expression and removal of DNA after conversion,” said Lauren N. Randolph, doctoral student in bioengineering, Penn State.

Previous approaches incorporated the appropriate DNA to switch on the conversions, but did not completely remove all the DNA inserted.

The researchers are using a Tet-On 3G inducible PiggyBac system that is a plasmid they named XLone to achieve insertion, activation and removal. The PiggyBac portion of the system includes the DNA to insert that DNA into the cell’s DNA. The Tet-On 3G portion contains the necessary signaling information. This system also makes the cells more sensitive to doxycycline, which is the drug used to initiate the conversion.

“We are using abundant multiple copies of the plasmid to increase the likelihood that it gets in and does what it is supposed to do and actually follows through reproduction of the cells,” said Lian.

If only one or a few plasmids are inserted into the cell, the new DNA could just be silenced. Insertion of multiple plasmids assures that at least one will function.

“The first advantage with our system is that it does not have any leakage expression,” said Randolph. “If we don’t induce the system with doxycycline, we get nothing.”

The second advantage is that once the cells are reproducing as heart cells or nerve cells, the plasmid can be removed and the cells continue to reproduce without any remnant of the plasmid system.

While the researchers are currently aiming to understand and study gene function and directed cell differentiation in human stem cells, eventually they would like to be able to create cell-based therapies.

Reference: Lauren N. Randolph, Xiaoping Bao, Chikai Zhou, Xiaojun Lian. An all-in-one, Tet-On 3G inducible PiggyBac system for human pluripotent stem cells and derivatives. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-01684-6

lroot on June 29th, 2017

Fit 70 Year Old

Is 70 the new 60? A new Stony Brook University-led study to be published in PLOS ONE uses new measures of aging to scientifically illustrate that one’s actual age is not necessarily the best measure of human aging itself, but rather aging should be based on the number of years people are likely to live in a given country in the 21st Century.

The study combines the new measures of aging with probabilistic projections from the United Nations and predicts an end to population aging in the U.S. and other countries before the end of the century. Population aging when the median age rises in a country because of increasing life expectancy and lower fertility rates is a concern for countries because of the perception that population aging leads to declining numbers of working age people and additional social burdens.

According to Warren Sanderson, Professor of Economics at Stony Brook University and the lead author, this study’s projections imply that as life expectancies increase people are generally healthier with better cognition at older ages and countries can adjust public policies appropriately as to population aging.

Population aging could peak by 2040 in Germany and by 2070 in China, according to the study, which combines measures of aging with probabilistic population projections from the UN. In the USA, the study shows very little population aging at all in the coming century.

Traditional population projections categorize “old age” as a simple cutoff at age 65. But as life expectancies have increased, so too have the years that people remain healthy, active, and productive. In the last decade, IIASA researchers have published a large body of research showing that the very boundary of “old age” should shift with changes in life expectancy, and have introduced new measures of aging that are based on population characteristics, giving a more comprehensive view of population aging.

The study combines these new measures with UN probabilistic population projections to produce a new set of age structure projections for four countries: China, Germany, Iran, and the USA.

“Both of these demographic techniques are relatively new, and together they give us a very different, and more nuanced picture of what the future of aging might look like,” says Professor Sanderson, also a researcher at IIASA. He wrote the article with Sergei Scherbov, leader of the Re-Aging Project at IIASA, and Patrick Gerland, chief of the mortality section of the Population Division of the United Nations.

One of the measures used in the paper looks at life expectancy as well as years lived to adjust the definition of old age. Probabilistic projections produce a range of thousands of potential scenarios, so that they can show a range of possibilities of aging outcomes.

For China, Germany, and the USA, the study showed that population aging would peak and begin declining well before the end of the century. Iran, which had an extremely rapid fall in fertility rate in the last 20 years, has an unstable age distribution and the results for the country were highly uncertain.

“We chose these four countries for analysis because they have very different population structures and projections, and so they allow us to test this methodology across a range of possible scenarios,” summarizes Scherbov.

Abstract: “We merge two methodologies, prospective measures of population aging and probabilistic population forecasts. We compare the speed of change and variability in forecasts of the old age dependency ratio and the prospective old age dependency ratio as well as the same comparison for the median age and the prospective median age. While conventional measures of population aging are computed on the basis of the number of years people have already lived, prospective measures are computed also taking account of the expected number of years they have left to live. Those remaining life expectancies change over time and differ from place to place. We compare the probabilistic distributions of the conventional and prospective measures using examples from China, Germany, Iran, and the United States. The changes over time and the variability of the prospective indicators are smaller than those that are observed in the conventional ones. A wide variety of new results emerge from the combination of methodologies. For example, for Germany, Iran, and the United States the likelihood that the prospective median age of the population in 2098 will be lower than it is today is close to 100 percent.”

Reference: Warren C. Sanderson, Sergei Scherbov, Patrick Gerland. Probabilistic population aging. PLOS ONE, 2017; 12 (6): e0179171 DOI: 10.1371/journal.pone.0179171

lroot on June 28th, 2017

Infinity Symbol

Emma Morano passed away last April. At 117 years old, the Italian woman was the oldest known living human being.

Super centenarians, such as Morano and Jeanne Calment of France, who famously lived to be 122 years old, continue to fascinate scientists and have led them to wonder just how long humans can live. A study published in Nature last October concluded that the upper limit of human age is peaking at around 115 years.

Now, however, a new study in Nature by McGill University biologists Bryan G. Hughes and Siegfried Hekimi comes to a starkly different conclusion. By analyzing the lifespan of the longest-living individuals from the USA, the UK, France and Japan for each year since 1968, Hekimi and Hughes found no evidence for such a limit, and if such a maximum exists, it has yet to be reached or identified, Hekimi says.

Far into the foreseeable future

“We just don’t know what the age limit might be. In fact, by extending trend lines, we can show that maximum and average lifespans, could continue to increase far into the foreseeable future,” Hekimi says. Many people are aware of what has happened with average lifespans. In 1920, for example, the average newborn Canadian could expect to live 60 years; a Canadian born in 1980 could expect 76 years, and today, life expectancy has jumped to 82 years. Maximum lifespan seems to follow the same trend.

It’s impossible to predict what future lifespans in humans might look like, Hekimi says. Some scientists argue that technology, medical interventions, and improvements in living conditions could all push back the upper limit.

“It’s hard to guess,” Hekimi adds. “Three hundred years ago, many people lived only short lives. If we would have told them that one day most humans might live up to 100, they would have said we were crazy.”

Reference: Bryan G. Hughes, Siegfried Hekimi. Many possible maximum lifespan trajectories. Nature, 2017; 546 (7660): E8 DOI: 10.1038/nature22786

lroot on June 15th, 2017

Toxins in Your Tap Water

America has a drinking water crisis. An NRDC study has found that contaminants that may harm human health are found in tap water in every state in the nation. This is a problem even for people who don’t drink tap water since water borne toxins can be absorbed through the skin and lungs while bathing and into food if used for cooking.

Established in 1974, the Safe Drinking Water Act is one of the bedrock environmental laws in the United States, consisting of rules that regulate about 100 contaminants found in drinking water. NRDC has documented serious problems with our outdated and deteriorating water infrastructure, widespread violations and inadequate enforcement of the Safe Drinking Water Act for more than 25 years.

The study shows that in 2015 alone, there were more than 80,000 reported violations of the Safe Drinking Water Act by community water systems. Nearly 77 million people were served by more than 18,000 of these systems with violations in 2015. These violations included exceeding health-based standards, failing to properly test water for contaminants, and failing to report contamination to state authorities or the public. What’s worse, 2015 saw more than 12,000 health-based violations in some 5,000 community water systems serving more than 27 million people.

In 2016, the publication “What’s in Your Water: Flint and Beyond” detailed the lead crisis in Flint, Michigan, and contextualized a larger, national crisis around lead in drinking water. The new study picks up where that one left off, detailing a stunning number of violations of the Safe Drinking Water Act around the nation.

1. Combined Disinfectants and Disinfection Byproducts

Exposure to these contaminants can lead to cancer and may be linked to reproductive impacts such as miscarriages and birth defects. In 2015, there were 11,311 violations (4,591 health-based) at community water systems serving 25,173,431 people (12,584,936 health-based). Formal enforcement measures were taken in 12.4 percent of all cases and 23.0 percent of health-based cases.

2. Total Coliform

The presence of coliforms in drinking water indicates that possible presence of organisms that can cause diarrhea, cramps, nausea, and headaches in otherwise-healthy people. These impacts can be much more serious and even life-threatening for children, the elderly, and immune-compromised people. In 2015, there were 10,261 violations (2,574 health-based) at community water systems serving 17,768,807 people (10,118,586 health-based). Formal enforcement was taken in 8.8 percent of cases (and 8.3 percent of health-based cases).

3. Combined Surface, Ground Water, and Filter Backwash Rules

Exposure to some of these pathogens, such as Cryptosporidium or Giardia, can cause severe gastrointestinal distress, nausea, and diarrhea. They can cause serious, life-threatening infections for the very young, elderly, and immune-compromised. In 2015 there were 5,979 violations (1,790 health-based) at community water systems serving 17,312,604 people (5,336,435 health-based). Formal enforcement was taken in 13.7 percent of cases (28.2 percent of health-based cases).

4. Nitrites and Nitrates

Exposure can lead to blue baby syndrome in infants (potentially leading to death in extreme cases), developmental effects, and cardiovascular disease. In extreme cases, blue baby syndrome can be severe and lead to death. In 2015, there were 1,529 violations (459 health-based) at community water systems serving 3,867,431 people (1,364,494 health-based). Formal enforcement action was taken in 11.3 percent of all cases (and 27.9 percent of health-based cases).

5. Lead and Copper

Exposure to lead is particularly toxic to children and can cause serious, irreversible damage to their developing brains and nervous systems. Lead exposure can also cause miscarriages and stillbirths in pregnant women, as well as fertility issues, cardiovascular and kidney effects, cognitive dysfunction, and elevated blood pressure in healthy adults. In 2015, there were 8,044 violations (303 health-based) by systems serving 18,350,633 people (582,302 health-based). Formal enforcement action was taken in 12.0 percent of the cases (and in 14.2 percent of health-based cases).

6. Radionuclides

Exposure can lead to cancers and compromised kidney function. In 2015, there were 2,297 violations (962 health-based) in community water systems serving 1,471,364 people (445,969 health-based). Formal enforcement was taken in 11.7 percent of all cases (and 16.1 percent of health-based cases).

7. Arsenic

A known human carcinogen, exposure can lead to cancers, development effects, pulmonary disease, or cardiovascular disease. In 2015, there were 1,537 violations (1,135 health-based) at community water systems serving 1,842,594 people (358,323 health-based). Formal enforcement was taken in 28.9 percent of cases (37.1 percent of health-based cases).

8. Synthetic Organic Contaminants

Exposure can lead to cancers, developmental effects, central nervous system and reproductive difficulties, endocrine issues, or liver and kidney problems. In 2015 there were 6,864 violations (17 health-based) serving 2,669,594 people (301,099 health-based). Formal enforcement action was taken in 7.3 percent of cases (and 5.9 percent of health-based cases).

9. Inorganic Contaminants

Exposure can lead to increased cholesterol, kidney damage, hair loss, skin irritation, and cancer. In 2015, there were 1,505 violations (291 health-based) in community water systems serving 1,312,643 people (83,033 health-based). Formal enforcement was taken in 5.2 percent of cases (15.1 percent of health-based cases).

10. Volatile Organic Contaminants

Exposure can lead to cancers; developmental, skin, and reproductive issues; and cardiovascular problems. Exposure can also cause adverse effects on the liver, kidneys, and immune and nervous systems. In 2015 there were 10,383 violations (15 of them health-based) at community water systems serving 3,451,072 people (5,276 health-based). Formal enforcement was taken in 6.1 percent of cases (and 26.7 percent of health-based cases).

11. Public Notification

All community water systems are required to directly deliver information about their drinking water quality to each customer once a year. In 2015 there were 13, 202 violations by community water systems serving 8,381,050 people. Formal enforcement action was taken in 10.3 percent of cases.

The take away from this is to either install a water purifier or use natural spring water. Purifiers are also available for showers and are typically installed between the shower head and pipe.

Walking my way to 100

New research from Brigham Young University reveals you may be able to slow one type of aging the kind that happens inside your cells. As long as you’re willing to sweat.

“Just because you’re 40, doesn’t mean you’re 40 years old biologically,” Tucker said. “We all know people that seem younger than their actual age. The more physically active we are, the less biological aging takes place in our bodies.”

The study, published in the medical journal Preventive Medicine, finds that people who have consistently high levels of physical activity have significantly longer telomeres than those who have sedentary lifestyles, as well as those who are moderately active.

Telomeres are the protein endcaps of our chromosomes. They’re like our biological clock and they’re extremely correlated with age; each time a cell replicates, we lose a tiny bit of the endcaps. Therefore, the older we get, the shorter our telomeres.

Exercise science professor Larry Tucker found adults with high physical activity levels have telomeres with a biological aging advantage of nine years over those who are sedentary, and a seven-year advantage compared to those who are moderately active. To be highly active, women had to engage in 30 minutes of jogging per day (40 minutes for men), five days a week.

“If you want to see a real difference in slowing your biological aging, it appears that a little exercise won’t cut it,” Tucker said. “You have to work out regularly at high levels.”

Tucker analyzed data from 5,823 adults who participated in the CDC’s National Health and Nutrition Examination Survey, one of the few indexes that includes telomere length values for study subjects. The index also includes data for 62 activities participants might have engaged in over a 30-day window, which Tucker analyzed to calculate levels of physical activity.

His study found the shortest telomeres came from sedentary people–they had 140 base pairs of DNA less at the end of their telomeres than highly active folks. Surprisingly, he also found there was no significant difference in telomere length between those with low or moderate physical activity and the sedentary people.

Although the exact mechanism for how exercise preserves telomeres is unknown, Tucker said it may be tied to inflammation and oxidative stress. Previous studies have shown telomere length is closely related to those two factors and it is known that exercise can suppress inflammation and oxidative stress over time.

“We know that regular physical activity helps to reduce mortality and prolong life, and now we know part of that advantage may be due to the preservation of telomeres,” Tucker said.

Reference: Larry A. Tucker. Physical activity and telomere length in U.S. men and women: An NHANES investigation. Preventive Medicine, Volume 100, July 2017, Pages 145–151

Bone Fracture

A Cedars-Sinai-led team of investigators has successfully repaired severe limb fractures in laboratory animals with an innovative technique that cues bone to regrow its own tissue. If found to be safe and effective in humans, the pioneering method of combining ultrasound, stem cell and gene therapies could eventually replace grafting as a way to mend severely broken bones.

“We are just at the beginning of a revolution in orthopedics,” said Dan Gazit, PhD, DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.”

Gazit was the principal investigator and co-senior author of the research study, published in the journal Science Translational Medicine.

More than 2 million bone grafts, frequently necessitated by severe injuries involving traffic accidents, war or tumor removal, are performed worldwide each year. Such injuries can create gaps between the edges of a fracture that are too large for the bone to bridge on its own. The grafts require implanting pieces from either the patient’s or a donor’s bone into the gap.

“Unfortunately, bone grafts carry disadvantages,” said Gazit, a professor of surgery at Cedars-Sinai. “There are huge unmet needs in skeleton repair.”

One problem is that enough healthy bone is not always available for repairs. Surgeries to remove a bone piece, typically from the pelvis, and implant it can lead to prolonged pain and expensive, lengthy hospitalizations. Further, grafts from donors may not integrate or grow properly, causing the repair to fail.

The new technique developed by the Cedars-Sinai-led team could provide a much-needed alternative to bone grafts.

In their experiment, the investigators constructed a matrix of collagen, a protein the body uses to build bones, and implanted it in the gap between the two sides of a fractured leg bone in laboratory animals. This matrix recruited the fractured leg’s own stem cells into the gap over a period of two weeks. To initiate the bone repair process, the team delivered a bone-inducing gene directly into the stem cells, using an ultrasound pulse and microbubbles that facilitated the entry of the gene into the cells.

Eight weeks after the surgery, the bone gap was closed and the leg fracture was healed in all the laboratory animals that received the treatment. Tests showed that the bone grown in the gap was as strong as that produced by surgical bone grafts, said Gadi Pelled, PhD, DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author.

“This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.”

The study involved six departments at Cedars-Sinai, plus investigators from Hebrew University in Jerusalem; the University of Rochester in Rochester, New York; and the University of California, Davis.

“Our project demonstrates how scientists from diverse disciplines can combine forces to find solutions to today’s medical challenges and help develop treatments for the patients of tomorrow,” said Bruce Gewertz, MD, surgeon-in-chief and chair of the Department of Surgery at Cedars-Sinai.

Reference: Maxim Bez, Dmitriy Sheyn, Wafa Tawackoli, Pablo Avalos, Galina Shapiro, Joseph C. Giaconi, Xiaoyu Da, Shiran Ben David, Jayne Gavrity, Hani A. Awad, Hyun W. Bae, Eric J. Ley, Thomas J. Kremen, Zulma Gazit, Katherine W. Ferrara, Gadi Pelled, Dan Gazit. In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs. Science Translational Medicine, 2017; 9 (390): eaal3128 DOI: 10.1126/scitranslmed.aal3128

lroot on June 2nd, 2017


Among all the organs in the human body, the liver is something of a superhero. Not only does it defend our bodies against the liquid toxins we regularly ingest, it has the ability to regenerate itself, and, as new research shows, it increases its size by nearly half over the course of a day.

Working in mice, researchers in Switzerland documented this process of regular stretching and shrinking, watching as liver cells swelled in size and contracted up to 40 percent along with the mice’s daily activities. There’s a catch though, a kind of hepatological kryptonite. Their livers only exhibited this ability when the mice followed their normal cycles of eating and resting. They’re nocturnal creatures, and if they began eating during the day when they usually rest, their livers stubbornly refused to grow.

The liver is the only organ known to display such significant cyclical growth, although it does make sense. During the half of the day when we’re not eating, our organs have far less to do. By growing and shrinking to meet demand, our livers are actually trying to save us wasted energy.

The Swiss researchers say that they observed hepatocytes, the main kind of cell in livers, growing during the night when mice were active, something they they attribute largely to an increase in ribosomes, structures in cells that take RNA instructions and use them to produce proteins, among other things. The liver takes material from the food and converts it into useful proteins and other molecules crucial for bodies to function, so possessing more ribosomes means they’re that much better at their jobs. When their daily cycle comes to a close, livers begin breaking down the ribosomes again, like street vendors packing up for the night.

It makes sense that livers would swell when they have to work the hardest. What the researchers found, though, was that it’s not just food intake that tells the liver to ramp up ribosome production — it’s also dependent on what time of day it is. Cells in our livers are also sensitive to circadian rhythms and they found that mouse livers would only begin to grow at night when they ate. Mice fed during the day did not exhibit the same kind of liver growth that their nocturnal counterparts did. The cues that tell the liver to begin preparing for action don’t just come from our food, in other words, they also come from the environment.

Because a bigger liver can work faster and pull out nutrients more efficiently, there’s an obvious advantage to maintaining this kind of cycle. In mice kept nocturnal, there was a noticeable smooth curve of growing and shrinking, and the researchers noticed a 1.6-fold difference in the level of proteins in the liver between the two extremes. In day-fed mice, there was no difference, indicating that their livers weren’t able to produce as much. They published their work Thursday in Cell.

There is evidence that human livers may exhibit the same ability based on a 1986 study that used ultrasound to measure people’s livers over the course of six hours. They found variations of around 20 percent, although they didn’t take any measurements during the night, when our bodily rhythms slow down.

These findings in the liver add to a mounting case for returning to sleep cycles based on environmental cues. Illuminating the night with artificial brilliance has been tied to disrupted sleep cycles in humans, as well as an increased risk for obesity, diabetes, depression and some types of cancer. For millennia, our bodies regulated themselves with the daily rising and setting of the sun, ramping us up when it was light and settling us back down when it got dark. Now, it appears that this extends to our digestive systems as well.

Our livers cleanse toxins from our bodies, produce proteins and chemicals necessary for digestion, recycle old red blood cells and regulate glycogen levels in our bodies. If they aren’t working properly, we can die. While the authors don’t address the implications of their work for humans, their findings could help to explain why it’s unhealthy to go to bed late at night.

Reference: Flore Sinturel, Alan Gerber, Daniel Mauvoisin, Jingkui Wang, David Gatfield, Jeremy J. Stubblefield, Carla B. Green, Frédéric Gachon, Ueli Schibler. Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles. Cell, Volume 169, Issue 4, 651 – 663