Stem Cells Regrow Damaged Teeth

healthy-teeth

The stem cells in our teeth can be energized to fill in chips, cracks, and cavities, researchers say, and the findings could one day possibly make dental cement obsolete.

The work has been conducted just in mice so far, but the research, published Monday in the journal Scientific Reports, highlights a way to motivate stem cells to repair tooth defects at a scale they normally can?t, with a drug that already has some safety testing behind it. It also demonstrates the potential of a type of stem cell therapy in which the cells are stimulated in place, rather than taken out, manipulated, and put back in.

?We?re mobilizing stem cells in the body and it works,? said Paul Sharpe, a researcher at King?s College London and an author of the new paper. ?If it works for teeth, chances are it could work for other organs.?

Experts not involved with the work noted that while it is in early stages, the simplicity of the approach should ease its path into the next phases of research that show whether it might produce the same results in people.

?These important steps close down the translational gap and bring this discovery a step closer to future clinical applications,? Dr. Vanessa Chrepa, a researcher at the University of Washington, wrote in an email. ?This work will hopefully set the stage for clinical studies in the near future.?

When teeth lose some of their dentin ? the bony tissue beneath the enamel that makes up the bulk of the tooth ? the stem cells tucked deep inside mount a recovery effort and manufacture new dentin (which is also spelled dentine). The problem, Sharpe said, is that the natural repair mechanism can only regrow small amounts of dentin and can?t make up all that is lost when a tooth suffers a serious injury, contracts a major infection, or takes on the sharp end of a dentist?s drill.

Because of the limits of the teeth?s ability to repair themselves, dentists have to fill or seal teeth to prevent further infection and degradation. But dental cement also prevents the tooth from ever returning to its natural, pearly white self.

Sharpe and his team have been trying to understand how the natural repair mechanism works in hopes of converting that understanding into a way to super-power it. As part of their research, they discovered that a group of molecules called glycogen synthase kinase inhibitors (or GSK-3 inhibitors) boosts the stem cells? ability to stimulate production of dentin beyond what normally occurs.

For the new study, the researchers drilled tiny holes into mice?s molars to expose the tooth?s pulp, where the stem cells live. They then inserted collagen sponges that had been soaked in one of three types of GSK-3 inhibitors and covered the tooth.

After six weeks, the researchers removed the teeth and found that the sponges had dissolved and the lost dentin had mostly been regenerated.

?They?ve harnessed the signaling pathway that promotes natural repair,? said Megan Pugach, a researcher at the Forsyth Institute in Cambridge, Mass., and at the Harvard School of Dental Medicine, who was not involved with the research.

Sharpe and his team are now conducting similar studies in rats to make sure the approach can generate enough dentin to fill in larger holes in larger teeth before trying to study the method in people. But two aspects of the approach could help ease its path into clinical trials.

Anti-Aging Effects of the Mediterranean Diet On Brain Health

mediterranean-diet

A new study shows that older people who followed a Mediterranean diet retained more brain volume over a three-year period than those who did not follow the diet as closely. The study is published in the January 4, 2017, online issue of Neurology?, the medical journal of the American Academy of Neurology. But contrary to earlier studies, eating more fish and less meat was not related to changes in the brain.

The Mediterranean diet includes large amounts of fruits, vegetables, olive oil, beans, whole grains, moderate amounts of fish, dairy and wine, and limited red meat and poultry.

“As we age, the brain shrinks and we lose brain cells which can affect learning and memory,” said study author Michelle Luciano, PhD, of the University of Edinburgh in Scotland. “This study adds to the body of evidence that suggests the Mediterranean diet has a positive impact on brain health.”

Researchers gathered information on the eating habits of 967 Scottish people around age 70 who did not have dementia. Of those people, 562 had an MRI brain scan around age 73 to measure overall brain volume, gray matter volume and thickness of the cortex, which is the outer layer of the brain. From that group, 401 people then returned for a second MRI at age 76. These measurements were compared to how closely participants followed the Mediterranean diet.

The participants varied in how closely their dietary habits followed the Mediterranean diet principles. People who didn’t follow as closely to the Mediterranean diet were more likely to have a higher loss of total brain volume over the three years than people who followed the diet more closely. The difference in diet explained 0.5 percent of the variation in total brain volume, an effect that was half the size of that due to normal aging.

The results were the same when researchers adjusted for other factors that could affect brain volume, such as age, education and having diabetes or high blood pressure.

There was no relationship between grey matter volume or cortical thickness and the Mediterranean diet.

The researchers also found that fish and meat consumption were not related to brain changes, which is contrary to earlier studies.

“It’s possible that other components of the Mediterranean diet are responsible for this relationship, or that it’s due to all of the components in combination,” Luciano said.

Luciano noted that earlier studies looked at brain measurements at one point in time, whereas the current study followed people over time.

“In our study, eating habits were measured before brain volume was, which suggests that the diet may be able to provide long-term protection to the brain,” said Luciano. “Still, larger studies are needed to confirm these results.”

Reference: 1.Michelle Luciano, Janie Corley, Simon R. Cox, Maria C. Vald?s Hern?ndez, Leone C.A. Craig, David Alexander Dickie, Sherif Karama, Geraldine M. McNeill, Mark E. Bastin, Joanna M. Wardlaw, Ian J. Deary. Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort. Neurology, 2017; 10.1212/WNL.0000000000003559 DOI: 10.1212/WNL.0000000000003559

Can Pomegranates Extend Youthful Vitality and Lifespan?

Pomegranates

Are pomegranates really the superfood we’ve been led to believe will counteract the aging process? Up to now, scientific proof has been fairly weak. And some controversial marketing tactics have led to skepticism as well. A team of scientists from EPFL wanted to explore the issue by taking a closer look at the secrets of this plump pink fruit. They discovered that a molecule in pomegranates, transformed by microbes in the gut, enables muscle cells to protect themselves against one of the major causes of aging. In nematodes and rodents, the effect is nothing short of amazing. Human clinical trials are currently underway, but these initial findings have already been published in the journal Nature Medicine.

As we age, our cells increasingly struggle to recycle their powerhouses. Called mitochondria, these inner compartments are no longer able to carry out their vital function, thus accumulate in the cell. This degradation affects the health of many tissues, including muscles, which gradually weaken over the years.

One molecule plays David against the Goliath of aging

The scientists identified a molecule that, all by itself, managed to re-establish the cell’s ability to recycle the components of the defective mitochondria: urolithin A. “It’s the only known molecule that can relaunch the mitochondrial clean-up process, otherwise known as mitophagy,” says Patrick Aebischer, co-author on the study. “It’s a completely natural substance, and its effect is powerful and measurable.”

The team started out by testing their hypothesis on the usual suspect: the nematode C. elegans. It’s a favorite test subject among aging experts, because after just 8-10 days it’s already considered elderly. The lifespan of worms exposed to urolithin A increased by more than 45% compared with the control group.

These initial encouraging results led the team to test the molecule on animals that have more in common with humans. In the rodent studies, like with C. elegans, a significant reduction in the number of mitochondria was observed, indicating that a robust cellular recycling process was taking place. Older mice, around two years of age, showed 42% better endurance while running than equally old mice in the control group.

Before heading out to stock up on pomegranates, however, it’s worth noting that the fruit doesn’t itself contain the miracle molecule, but rather its precursor. That molecule is converted into urolithin A by the microbes that inhabit the intestine. Because of this, the amount of urolithin A produced can vary widely, depending on the species of animal and the flora present in the gut microbiome. Some individuals don’t produce any at all. If you’re one of the unlucky ones, it’s possible that pomegranate juice won’t do you any good.

For those without the right microbes in their guts, however, the scientists are already working on a solution. The study’s co-authors founded a start-up company, which has developed a method to deliver finely calibrated doses of urolithin A. The company is currently conducting first clinical trials testing the molecule in humans in European hospitals.

According to study co-author Johan Auwerx, it would be surprising if urolithin A weren’t effective in humans. “Species that are evolutionarily quite distant, such as C elegans and the rat, react to the same substance in the same way. That’s a good indication that we’re touching here on an essential mechanism in living organisms.”

Urolithin A’s function is the product of tens of millions of years of parallel evolution between plants, bacteria and animals. According to Chris Rinsch, co-author, this evolutionary process explains the molecule’s effectiveness: “Precursors to urolithin A are found not only in pomegranates, but also in smaller amounts in many nuts and berries. Yet for it to be produced in our intestines, the bacteria must be able to break down what we’re eating. When, via digestion, a substance is produced that is of benefit to us, natural selection favors both the bacteria involved and their host. Our objective is to follow strict clinical validations, so that everyone can benefit from the result of these millions of years of evolution.”

Reference: 1.Dongryeol Ryu, Laurent Mouchiroud, P?n?lope A Andreux, Elena Katsyuba, Norman Moullan, Amandine A Nicolet-dit-F?lix, Evan G Williams, Pooja Jha, Giuseppe Lo Sasso, Damien Huzard, Patrick Aebischer, Carmen Sandi, Chris Rinsch & Johan Auwerx. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, July 2016 DOI: 10.1038/nm.4132

Plant Pigment Linked To Cognitive Performance Across Lifespan

Stem Cells

A large study of older adults links consumption of a pigment found in leafy greens to the preservation of “crystallized intelligence,” the ability to use the skills and knowledge one has acquired over a lifetime.

The nutrient is lutein and the study is reported in the journal Frontiers in Aging Neuroscience.

Humans acquire lutein through the diet, primarily by eating leafy green vegetables, cruciferous vegetables such as broccoli, or egg yolks, according to University of Illinois graduate student Marta Zamroziewicz, who led the study with Illinois psychology professor Aron Barbey. It accumulates in the brain, embedding in cell membranes, where it likely plays “a neuroprotective role,” she said.

Lutein is also available as a dietary supplement which is typically extracted from the marigold plant and taken at a dosage of 20 mg per day. Most health food stores carry lutein which is often combined with zeaxanthin another nutrient from marigolds.

“Previous studies have found that a person’s lutein status is linked to cognitive performance across the lifespan,” Zamroziewicz said. “Research also shows that lutein accumulates in the gray matter of brain regions known to underlie the preservation of cognitive function in healthy brain aging.”

The study enrolled 122 healthy participants aged 65 to 75 who solved problems and answered questions on a standard test of crystallized intelligence. Researchers also collected blood samples to determine blood serum levels of lutein and imaged participants’ brains using MRI to measure the volume of different brain structures.

The team focused on parts of the temporal cortex, a brain region that other studies suggest plays a role in the preservation of crystallized intelligence.

The researchers found that participants with higher blood serum levels of lutein tended to do better on tests of crystallized intelligence. Serum lutein levels reflect only recent dietary intakes, Zamroziewicz said, but are associated with brain concentrations of lutein in older adults, which reflect long-term dietary intake.

Those with higher serum lutein levels also tended to have thicker gray matter in the parahippocampal cortex, a brain region that, like crystallized intelligence, is preserved in healthy aging, the researchers report.

“Our analyses revealed that gray-matter volume of the parahippocampal cortex on the right side of the brain accounts for the relationship between lutein and crystallized intelligence,” Barbey said. “This offers the first clue as to which brain regions specifically play a role in the preservation of crystallized intelligence, and how factors such as diet may contribute to that relationship.”

“Our findings do not demonstrate causality,” Zamroziewicz said. “We did find that lutein is linked to crystallized intelligence through the parahippocampal cortex.”

“We can only hypothesize at this point how lutein in the diet affects brain structure,” Barbey said. “It may be that it plays an anti-inflammatory role or aids in cell-to-cell signaling. But our finding adds to the evidence suggesting that particular nutrients slow age-related declines in cognition by influencing specific features of brain aging.”

Study Reference: Marta K. Zamroziewicz, Erick J. Paul, Chris E. Zwilling, Elizabeth J. Johnson, Matthew J. Kuchan, Neal J. Cohen, Aron K. Barbey. Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults. Frontiers in Aging Neuroscience, 2016; 8 DOI: 10.3389/fnagi.2016.00297

Staying Young and Extending Life By Resetting Blood Proteins

Stem Cells

A number of studies have been done where older animals were given blood from younger animals to find out if that would increase life span. It did and also improved the health of the older animals. In a new study, scientists are trying to reverse aging in older humans by filtering bad proteins from their blood and return it to a more youthful state. This comes after a study on mice showed that the procedure had some promise. For instance there was evidence that the blood cells from the younger mice produced muscle repair in the older mice. Now researchers from California are trying to replicate the results in older people in a clinical trial. The aim of this radical approach is to alter levels of bad proteins in the blood of older people. These proteins are believed to be responsible for hampering the growth of healthy tissue. This could help in the prevention of age-related disease and possibly slow down the aging process. The study was published in the journal Nature Communications.

This is part of what we are doing with Stem Cell 100 and Stem Cell 100+. They contain compounds for instance that up regulate longevity genes and help the blood and tissues to a younger state. Of course this occurs over time.

The animal study was co-funded by Calico, which is a life extension company owned by Google. The experiment was reversed on mice with old blood infused into young mice. The results showed a reduction in new liver and brain cells in the young mice and impaired performance in strength. This gave more credibility to the original experiment. In the human trial, older blood will pass through a machine that will try to reset proteins to a healthier level in the hope that body tissues will be properly maintained thus slowing down aging.

This new study is one of many that show key molecules in the blood can alter the pace of aging in body tissue. When these proteins are at low levels the body is healthy, but as we get older these protein levels can change. The team is now considering a more practical approach to control the levels of the proteins without blood transfusions. According to one scientist, these new treatments could prevent diabetes, Alzheimer’s, and Parkinson?s disease.

Another scientist Tony Wyss-Coray, from Stanford University was not convinced by the study and pointed out that only four pairs of mice were used in the experiment. In past experiments on animals, a procedure called parabiosis was used to swap blood between animals by conjoining them surgically. In this study, scientists did not use surgery but instead transferred blood through a tube and pump controlled by a computer.

The team is now working on devices that filter blood in more advanced ways to reduce high levels of the bad proteins. This will return the proteins to more youthful levels. The key here is to remove the inhibitor molecules and then to return the filtered blood back to the recipient. This medical procedure could result in life extension that could give people an extra three decades of life without any critical illnesses. This advanced treatment could become available within 3 years.

The Berkley team is currently brainstorming for ideas on how to normalize the levels of one particular protein considered to be the inhibitor. They hope clinical trials will start within six months and start producing results within three years. Scientist could be on the verge of transforming our lives by slowing the aging process and stopping age-related diseases.

References: Justin Rebo, Melod Mehdipour, Ranveer Gathwala, Keith Causey, Yan Liu, Michael J. Conboy & Irina M. Conboy. A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature Communications, 2016; doi:10.1038/ncomms13363

Colon Bacteria Turn Host Genes On or Off Depending Upon Diet

Colon Bacteria

New research provides further evidence of the important role that gut microbes play in health by revealing they alter host gene expression in a diet-dependent manner. Using mice, the researchers discovered that a Western diet prevents many of the gene expression changes of a plant rich diet. This provides important and additional evidence of the importance of eating lots of fruits and vegetables.

A study of the relationship between colon bacteria, diet and the genes of the host by a team at the University of Wisconsin-Madison (UW-Madison) was published in the journal Molecular Cell.

Genes found in strips of DNA contained in chromosomes are the blueprint for making organisms and sustaining life. However, while their DNA makeup is relatively fixed, genes respond to changes in environment.

Interactions with the environment do not change the genes, but they alter their expression by switching them on and off through chemical tags on the DNA.

The complete set of genetic material contained in our genes is called the genome, and the multitude of molecules that tell the genome what to do is called the epigenome.

Our gut is home to trillions of microbes altogether, they can weigh up to 2 kilograms. They not only help to digest food via fermentation, but in the process produce molecules called metabolites that influence health and disease for instance, to improve immune function and defend against infection.

In their paper, the UW-Madison researchers explain that while we have discovered that the colonies of microbes in our digestive tract collectively termed the gut microbiota produce a myriad of metabolites that affect health and disease, the underlying molecular mechanisms are poorly understood.

For their study, the researchers used mice raised on two different diets: one rich in plant carbohydrates (mimicking a human diet rich in fruits and vegetables) and the other high in simple sugars and fats (mimicking a Western diet).

The researchers found that a small group of short-chain fatty acids metabolites produced when gut bacteria ferment nutrients from plants were communicating with the cells of the host animals through the epigenome.

One of the investigators, John M. Denu, a UW-Madison professor of biomolecular chemistry and a senior researcher at the Wisconsin Institute for Discovery, says the short-chain fatty acids, and potentially many others, are partially responsible for the communication with epigenome.

When Prof. Denu and colleagues compared the mice fed on a Western-style diet with the ones on a diet rich in plant carbohydrates, they found the Western-style diet prevents many of the epigenetic changes that occur in the plant-rich diet.

In a further set of experiments, the researchers then supplemented the diet of mice raised in a germ-free environment (so they have no gut microbiota to speak of) with the short-chain fatty acids metabolites of gut bacteria fermentation.

They found that the short-chain fatty acid supplements restored the types of epigenetic changes seen in normal mice raised on the plant-rich diet.

Prof. Denu suggests their findings help show “the collection of three short-chain fatty acids produced in the plant-based diet are likely major communicators. We see that it is not just the microbe. It’s microbial metabolism.”

He and his colleagues also note that while foods rich in fat and sugar – hallmarks of the Western diet are more easily digested, they are not necessarily a good source of nutrients for gut microbes. This results in a less diverse microbiome, and less communication with the epigenome, they suggest.

They conclude that their findings have “profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health.”

Another surprising result of the study is that the communication between the gut microbiome and the host reaches beyond the colon. For example, the team found evidence of communication with cells of the liver and fatty tissue of the gut.

Can Lost Neurons Be Replaced?

Neurons

The human brain is a biological wonder with considerable skills. Regeneration, unfortunately, isn?t one of them.

Save for one tiny V shaped region within the hippocampus, the human brain?s ability to rebuild itself is limited. When neurons die, there?s no backup reserve of cells to replace them. Brain trauma such as a blow to the head, a stroke, or neurodegeneration can be brutally final. You?re not getting lost neurons back.

An obvious solution is to supply a broken brain with additional neurons, like swapping a broken stick of RAM with a new one. But a single neuron forms thousands of intricate connections to others near and far, and often these connections are established early in development.

Can a foreign transplant really assimilate into mature neuronal networks after injury and automatically repair broken circuitry? According to a new study recently published in Nature, the answer is a promising yes.

In mice with brain lesions, a German team showed that within two months of transplantation, foreign embryonic neurons matured and fully incorporated into an existing network within the hosts? visual brain region.

Amazingly, the adoptee neurons were nearly indistinguishable from the brain?s native ones and they carried the right information, established functional input and output circuitries, and performed the functions of the damaged neurons.

“To date, this is the most comprehensive study of the circuit integration of transplanted neurons into the adult brain, and the only study so far to follow the integration of individual cells throughout their life span in the new host,” says study author Susanna Falkner, a PhD student at the Max Planck Institute of Neurobiology to Singularity Hub.

It?s a tour de force demonstration of brain plasticity that gives hope to cell transplantation therapies for devastating brain disorders like traumatic brain injury, Parkinson?s and Alzheimer?s disease.

Cell transplantation studies are nothing new, but almost all previous studies used infant animals rather than adults as hosts.

“Early postnatal brains are still developing and thus are much more plastic and receptive for grafts,” explains Falkner.

Although a handful of attempts at grafting stem cells into adult mice brains have been published, so far no one has convincingly demonstrated that the grafts could mature and function in a foreign brain.

To start off, the team used a powerful laser to precisely damage a small bit of brain tissue within a mouse?s visual cortex.

The scientists picked the brain region with care. “We know so much about the functions of the nerve cells in this region and the connections between them that we can readily assess whether the implanted nerve cells actually perform the tasks normally carried out by the network, ” explains study author Dr. Mark H?bener.

They then isolated immature neurons from the outermost layer of mice embryos and labeled them with a fluorescent protein tag. Under the microscope, these tags light up in brilliant reds and greens, which makes the transplanted cells easily distinguishable from the host?s native neurons. Using a long, thin needle, the embryonic neurons were then injected straight into the damaged mouse cortex.

The team next carefully crafted a “cranial window” by removing parts of the skull above the injection site and fitting it with a clear glass panel. This way, scientists were able to observe individual neurons for long periods of time through the window without harming the delicate cortex or risking infection.

Over the course of just a month, the transplanted neurons sprouted long, tortuous branches characteristic of cortical neurons. Tiny mushroom shaped structures called spines popped up on the neurons? output wires (dendrites), a process often seen in normal brain development. Since synapses grow on these bulbous spines, this suggested that the transplants were actively forming connections with other neurons in the brain.

One month after transplantation, the team mapped the newly added neurons? connections of which brain regions they projected to and which regions they received information from. Not only was the wiring exquisitely accurate, with some extending across the entire brain, the strengths of those connections were also similar to those formed by the laser ablated neurons.

“The very fact that the cells survived and continued to develop was very encouraging,” says H?bener. “But things got really exciting when we took a closer look at the electrical activity of the transplanted cells.”

Neurons from a part of the visual cortex called V1 are very picky about what sorts of stimuli they respond to. For example, a neuron may only fire when it detects black and white lines presented at a 45 degree angle, but not at any other angles. This is called tuning, which develops early in life. Promiscuous V1 neurons are bad news without selective activation, they pump noise into the circuit.

By 15 weeks after transplantation, the new neurons adopted the functional quirks of V1 neurons, consistently responding more strongly towards certain line orientations than others. They remained fully functional for the entire year long duration of the study.

“These findings demonstrate that the implanted nerve cells have integrated with high precision into a neuronal network into which, under normal conditions, new nerve cells would never have been incorporated,” explains lead author Dr. Magdalena Gotz at the Ludwig Maximilians University in Munich, Germany.

So what does this mean for repairing a degenerating human brain?

“This proof of principle study shows that?the lesioned adult brain is still capable of integrating new building blocks,” says Falkner. “Neuronal replacement therapies may be realistic, at least at times when a sufficient part of the pre-existing neuronal network is still available.”

Cell replacement therapy has been tried in Parkinson?s disease for at least two decades, but with mixed results. Impure sources of donor cells, pre-implant processing, suboptimal grafting procedures and side effects could all contribute, explains Falker.

Then there?s the issue that real world brain injuries aren?t so sterile and precise. A whack to the head, for example, can trigger inflammatory and other signals that turn the brain into a hostile environment unreceptive to neuron implants.

But the team is hopeful that their regime can help in those situations as well.

“We are doing this now in more realistic models, in models of traumatic and ischemic brain injury and all I can say is that it looks pretty good,” says Gotz.

Supply is also a problem isolating neurons from aborted fetuses isn?t a practical solution but recent advances in cell reprogramming could be a readily available answer.

Scientists can already directly turn skin cells into neurons, for example. Other groups have also shown that glia cells the other major cell type in the brain can shed their identity and transform into neurons under the right conditions. Then there are iPSCs, in which a patient?s skin cell is deprogrammed into stem cells and further developed into neurons.

It?s becoming more possible to get defined mixtures of cells to match the afflicted cell type in the diseased brain, says Falkner.

“Once neurons die, there is, at the moment, no real therapy to make these neurons come back. Surely, at some point in the future, these approaches will be used in the clinic,” says Gotz.

How Anti-Aging Can Save the Economy

Global Increase in Aging Population

The human race is now going through the biggest macroeconomic change in history. This change has two faces. First, life expectancies have nearly doubled in the West since the beginning of the 20th century. This change is even more rapid in formerly undeveloped regions as they catch up to Western technologies.

The other aspect is falling birth rates, which seem correlated to longer life spans. Fertility rates (births per woman) have fallen below replacement rates globally for the first time ever. And in many developed countries, fertility rates are alarmingly low.

A fertility rate of at least 2.1 children per woman is needed for native population stability in the West. It can be 2.5 or more where infant mortality is higher.

Japan and Germany are now at about 1.4 children per woman and falling. Singapore, Greece, and Spain are at about 1.3 births per woman. Within decades, whole nations will be at 1 birth per woman.

This means the next generation will be half the size of the last.

Every generation, from now on, will be smaller than the last. For economists and demographers, this problem is represented by the old-age dependency ratio (OADR).
The OADR refers to the number of people in a society who contribute to the economy compared to those who depend on transfer payments of some kind. Most social programs for the aged as well as pension plans were developed when the OADR was much healthier.

As life spans have lengthened, the OADR has deteriorated. There are two reasons for this. Longer lives mean that more people are moving to the dependent column of the balance sheet. At the same time, falling birth rates have reduced the number of workers in the contributor column.

In 1950, there were about 17 workers in America for every retired person. Today, there are less than three contributors to each retired dependent. This ratio continues to worsen simply because people are living longer and birth rates are falling.

In the US today, politicians say that the economy is doing fine. But if that were true, we?d be running budget surpluses. Instead, the US government is borrowing nearly 30 cents of every dollar spent. Transfer payments to the elderly now account for about 30% of federal spending. The roughly $20 trillion dollar national debt continues to grow, and unfunded liabilities are 10 to 20 times that amount (depending on who?s doing the math).

Former head of the Federal Reserve Allen Greenspan has long been known as an optimist. He?s held the view that market forces are robust enough to counter political recklessness. But recently, Greenspan admitted that he has lost his positive outlook. The reason, in his words, is that ?we have a 9% annual rate of increase in entitlements, which is mandated by law. It has got nothing to do with the economy. It has got to do with age and health and the like.?

Our current economic woes aren?t rooted in traditional economic policies. The problem is ?age and health and the like.? In other words, it?s the OADR.

Increasing the number of people on the contributor side of the balance sheet won?t solve the problem. Japan, Germany, Italy, and the Scandanavian countries have spent billions trying to increase birth rates. And they?ve failed. Even if they succeeded, it wouldn?t help in time. It takes decades for newborns to enter the work force.

The best way to prevent the demise of Western economies and the eventual Greek-style collapse of social programs and pension plans is longer life and health spans. If more people can remain healthy and work or invest longer, it would produce the economic growth we need to fund the innovation that will usher in an unparalleled era of prosperity.

Politicians and unions claim that voters won?t accept an increase in retirement ages, but Americans are already working longer than ever before. In fact, the evidence shows that most people would work longer and save more to pay their own way if they could.

According to a study by Zoya Financial, almost two-thirds of Americans have to retire earlier than planned. This is largely due to problems with their health or that of their spouse.

Anti-aging strategies and biotechnologies aren?t just needed from the point of view of the individual. They are, quite literally, the only way to save modern economies from the unintended consequences of increased life spans? the collapsing OADR.

The mainstream scientific community is starting to accept that we must move from a model of disease treatment to anti-aging. Effective anti-aging therapeutics are in labs right now and will greatly increase health spans and working careers, saving Western economies and cultures from ruin in the process.

Bureaucratic and political inertia, though, is slowing the approval and adoption of these life and economy-saving solutions. The establishment will eventually come around, but only kicking and screaming.

Hence the world truly needs more medical professionals, and patients who can spread the word that the old model of treating diseases is obsolete, inhumane, and fiscally suicidal.

~ Written by Patrick Cox

Regenerating Damaged Nerves

Spinal Cord

Injuries to the spinal cord often cause paralysis and other permanent disabilities because severed nerve fibers do not regrow on their own. During the past few years a number of paralyzed patients have experienced remarkable improvement as a result of Stem Cell Therapy. When their own stem cells or those extracted from cord blood were injected into the spinal column they went straight to the damaged nerves and helped them regenerate. One limitation is that the treatment must be given as soon as possible after the injury. When the same injections were given to patients who had been paralyzed for a year or more they were rarely successful. During the first few months after a spinal injury the nerves lose their ability to regenerate even with the introduction of new stem cells.

Now, scientists of the German Center for Neurodegenerative Diseases (DZNE) have succeeded in releasing a molecular brake that prevents the regeneration of nerve connections. Treatment of mice with Pregabalin, a drug that acts upon the growth inhibiting mechanism, caused damaged nerve connections to regenerate. Researchers led by neurobiologist Frank Bradke report on these findings in the journal Neuron.

Human nerve cells are interconnected in a network that extends to all parts of the body. In this way control signals are transmitted from head to toe, while sensory inputs flow in the opposite direction. For this to happen, impulses are passed from neuron to neuron, not unlike a relay race. Damages to this wiring system can have drastic consequences particularly if they affect the brain or the spinal cord. This is because the cells of the central nervous system are connected by long projections. When severed, these projections, which are called axons, are unable to regrow.

Neural pathways that have been injured can only regenerate if new connections arise between the affected cells. In a sense, the neurons have to stretch out their arms, i.e. the axons have to grow. In fact, this happens in the early stages of embryonic development. However, this ability disappears in the adult. Can it be reactivated? This was the question Professor Bradke and co-workers asked themselves. “We started from the hypothesis that neurons actively down-regulate their growth program once they have reached other cells, so that they don’t overshoot the mark. This means, there should be a braking mechanism that is triggered as soon as a neuron connects to others,” says Dr. Andrea Tedeschi, a member of the Bradke Lab and first author of the current publication.

In mice and cell cultures, the scientists started an extensive search for genes that regulate the growth of neurons. “That was like looking for the proverbial needle in the haystack. There are hundreds of active genes in every nerve cell, depending on its stage of development. To analyze the large data set we heavily relied on bioinformatics. To this end, we cooperated closely with colleagues at the University of Bonn,” says Bradke. “Ultimately, we were able to identify a promising candidate. This gene, known as Cacna2d2, plays an important role in synapse formation and function, in other words in bridging the final gap between nerve cells.” During further experiments, the researchers modified the gene’s activity, e.g. by deactivating it. In this way, they were able to prove that Cacna2d2 does actually influence axonal growth and the regeneration of nerve fibers.

Cacna2d2 encodes the blueprint of a protein that is part of a larger molecular complex. The protein anchors ion channels in the cell membrane that regulate the flow of calcium particles into the cell. Calcium levels affect cellular processes such as the release of neurotransmitters. These ion channels are therefore essential for the communication between neurons.

In further investigations, the researchers used Pregabalin (PGB), a drug that had long been known to bind to the molecular anchors of calcium channels. Over a period of several weeks, they administered PGB to mice with spinal cord injuries. As it turned out, this treatment caused new nerve connections to grow.

“Our study shows that synapse formation acts as a powerful switch that restrains axonal growth. A clinically-relevant drug can manipulate this effect,” says Bradke. In fact, PGB is already being used to treat lesions of the spinal cord, albeit it is applied as a pain killer and relatively late after the injury has occurred. “PGB might have a regenerative effect in patients, if it is given soon enough. In the long term this could lead to a new treatment approach. However, we don’t know yet.”

In previous studies, the DZNE researchers showed that certain cancer drugs can also cause damaged nerve connections to regrow. The main protagonists in this process are the microtubules, long protein complexes that stabilize the cell body. When the microtubules grow, axons do as well. Is there a connection between the different findings? “We don’t know whether these mechanisms are independent or whether they are somehow related,” says Bradke. “This is something we want to examine more closely in the future.”

Hyperelastic Bone – Regeneration Breakthrough

Stem Cell Clinics Map

A Northwestern Engineering research team has developed a 3-D printable ink that produces a synthetic bone implant that rapidly induces bone regeneration and growth. This hyperelastic “bone” material, whose shape can be easily customized, one day could be especially useful for the treatment of bone.

Bone implantation surgery is never an easy process, but it is particularly painful and complicated for children. With both adults and children, often times bone is harvested from elsewhere in the body to replace the missing bone, which can lead to other complications and pain. Metallic implants are sometimes used, but this is not a permanent fix for growing children.

“Adults have more options when it comes to implants,” said Ramille N. Shah, who led the research. “Pediatric patients do not. If you give them a permanent implant, you have to do more surgeries in the future as they grow. They might face years of difficulty.”

Shah and her team aim to change the nature of bone implants, and they particularly want to help pediatric patients. Shah is an assistant professor of materials science and engineering in Northwestern’s McCormick School of Engineering and of surgery in the Northwestern University Feinberg School of Medicine.

The new study, evaluating the material with human stem cells and within animal models, was published online September 28 by the journal Science Translational Medicine. Adam E. Jakus, a postdoctoral fellow in Shah’s laboratory, is the paper’s first author.

Shah’s 3-D printed biomaterial is a mix of hydroxyapatite (a calcium mineral found naturally in human bone) and a biocompatible, biodegradable polymer that is used in many medical applications, including sutures. Shah’s hyperelastic “bone” material shows great promise in in vivo animal models; this success lies in the printed structure’s unique properties. It’s majority hydroxyapatite yet hyperelastic, robust and porous at the nano, micro and macro levels.

“Porosity is huge when it comes to tissue regeneration, because you want cells and blood vessels to infiltrate the scaffold,” Shah said. “Our 3-D structure has different levels of porosity that is advantageous for its physical and biological properties.”

While hydroxyapatite has been proven to induce bone regeneration, it is also notoriously tricky to work with. Clinical products that use hydroxyapatite or other calcium phosphate ceramics are hard and brittle. To compensate for that, previous researchers created structures composed mostly of polymers, but this shields the activity of the bioceramic. Shah’s bone biomaterial, however, is 90 percent by weight percent hydroxyapatite and just 10 percent by weight percent polymer and still maintains its elasticity because of the way its structure is designed and printed. The high concentration of hydroxyapatite creates an environment that induces rapid bone regeneration.

“Cells can sense the hydroxyapatite and respond to its bioactivity,” Shah said. “When you put stem cells on our scaffolds, they turn into bone cells and start to up-regulate their expression of bone specific genes. This is in the absence of any other osteo-inducing substances. It’s just the interaction between the cells and the material itself.”

That’s not to say that other substances couldn’t be combined into the ink. Because the 3-D printing process is performed at room temperature, Shah’s team was able to incorporate other elements, such as antibiotics, into the ink.

“We can incorporate antibiotics to reduce the possibility of infection after surgery,” Shah said. “We also can combine the ink with different types of growth factors, if needed, to further enhance regeneration. It’s really a multi-functional material.”

One of the biggest advantages, however, is that the end product can be customized to the patient. In traditional bone transplant surgeries, the bone — after it’s taken from another part of the body — has to be shaped and molded to exactly fit the area where it is needed. Physicians would be able to scan the patient’s body and 3-D print a personalized product using Shah’s synthetic material. Alternatively, due to its mechanical properties, the biomaterial can also be easily trimmed and cut to size and shape during a procedure. Not only is this faster, but alsoless painful compared to using autograft material.

Shah imagines that hospitals may one day have 3-D printers, where they can print customized implants while the patient waits.

“The turnaround time for an implant that’s specialized for a customer could be within 24 hours,” Shah said. “That could change the world of craniofacial and orthopaedic surgery, and, I hope, will improve patient outcomes.”

Reference: 1.A. E. Jakus, A. L. Rutz, S. W. Jordan, A. Kannan, S. M. Mitchell, C. Yun, K. D. Koube, S. C. Yoo, H. E. Whiteley, C.-P. Richter, R. D. Galiano, W. K. Hsu, S. R. Stock, E. L. Hsu, R. N. Shah. Hyperelastic “bone”: A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial. Science Translational Medicine, 2016; 8 (358): 358ra127 DOI: 10.1126/scitranslmed.aaf7704