Entries in Lifespan Extension (5)

Thursday
Jul072016

YOUNG BLOOD REJUVENATES OUR CELLS

 

 

IT SOUNDS like the dark plot of a vampire movie – Young blood rejuvenates our cells. In October 2014, people with Alzheimer’s disease started to be injected with the blood of young people in the hope that it will reverse some of the damage caused by that condition. But holds promise for individuals suffering for a wide range issues that have impacted their body and effected the quality of their life style. Just imagine the implications of reversing Traumatic Brain Injuries, Parkinson’s, MS, ALS, Repairing Damaged Organs, Surgical Healing, Aging of Skin, Muscle and Vascular Development.

In the first human trial of the effects of young blood, at Stanford University, infusions of blood plasma from young people are being given to older people. The preliminary results have surprised the research team, since it appears that young blood rejuvenates all of the cells within the recipients’ bodies are showing marked improvement.

 

The scientists behind the experiment have evidence on their side that young blood rejuvenates. Work in animals has shown that a transfusion of young mouse blood can improve cognition and the health of several organs in older mice. It could even make those animals look younger. The ramifications for the cosmetics and pharmaceutical industries could be huge, if the same thing happens in people.

The study was published in Nature Medicine in 2014. Immediately, emails flooded in to Wyss-Coray’s inbox. Alzheimer’s patients wanted infusions of young blood. So did numerous aged billionaires interested in the potential that young blood rejuvenates. One, who flies around in a jet with his name emblazoned on the side, invited Wyss-Coray to an Oscars after-party this year. (He didn’t go.) Another correspondent wrote with a more disturbing offer: he said he could provide blood from children of whatever age the scientists required. Wyss-Coray was appalled. “That was creepy,” he said.

But it wasn’t until spring 2012 that plans to form a company emerged. Nikolich, an entrepreneur and neuroscientist at Stanford, had flown to Hong Kong to visit the family of Chen Din-hwa, a Chinese billionaire known as the King of Cotton Yarn. Three years earlier, Chen had died, aged 89, with Alzheimer’s disease. His grandson told Nikolich that towards the end of his life, Chen barely recognised his own family. Then he had a plasma transfusion for an unrelated condition, which seemed to have a spectacular effect. His mind was clearer and he was suddenly cogent. His grandson indicated that Alzheimer’s disease seem to historical effect the male of the family often at an early age.

Nikolich told them about Wyss-Coray’s research and the potential for plasma-based therapies that revitalised the ageing brain. Before long, the conversation turned to starting a company. The family invested a year later. The money got Alkahest established and ready to launch the first human trial of young plasma.

Alkahest’s ultimate goal – to identify the key proteins in plasma that rejuvenate or age human tissues and then manufacture a product that uses them – could take 10 to 15 years. In the near term, the company has another strategy. Earlier this year, the Spanish blood products firm,Grifols, pledged $37.5m for a 45% stake in Alkahest. With another $12.5m, the company will bankroll more research in exchange for rights to Alkahest’s first products. Over the next two years, Alkahest will take human plasma and divide it into fractions that are rich in different proteins. Each fraction will then be tested in mice to see if they boost brain function. Any that do will be swiftly introduced into human trials and developed into the first generation of products.

The Alkahest trial is small. Sha, a specialist in behavioral neurology, can enroll only 18 people aged 50 to 90 with mild to moderate Alzheimer’s disease. Each receives a unit of young human plasma or saline once a week for four weeks. They have the next six weeks off, then have four more weeks of infusions. Those who had plasma first time around get saline and vice versa. The process is blinded, so neither the patients, nor their carers, nor Sha herself, know who is receiving what. Throughout the trial, doctors will look for cognitive improvements. Only at the end of the trial, as soon as October this year, will Sha analyse the findings.

If patients improve with infusions of young plasma, scientists will be ecstatic. But the finding, indicating that young blood rejuvenates, would need to be replicated, ideally at other hospitals, and in more patients, in order to convince researchers. If any benefits stand the test of time, the studies will move on, to tease out the best doses and ages at which to give plasma, how patients’ brains change, and whether improvements make a real difference to the life of someone who can no longer recognize their own family.

Then there is safety. Toying with the ageing process might backfire. Rando is concerned that pumping pro-youthful proteins into people for years could end up giving them cancer. Wyss-Coray agrees it is a worry, but points out that long-term growth hormone therapy appears to be safe. “We just don’t know yet whether or not it will be a problem,” he said.

Rando is more upbeat about infusing patients with pro-youthful proteins for short periods. An elderly person having surgery might get an infusion to help them heal like a teenager. “Let’s say it works. If you can target tissues and improve wound healing in older people, that would be a feasible approach. It would not be about making 90-year-olds younger, or having people live to 150. It’s about healthy living, not longer living,” he said.

In the first human trial of the effects of young blood, at Stanford University, infusions of blood plasma from young people are being given to older people. The preliminary results have surprised the research team, since it appears that all of the cells within the recipients’ bodies are showing marked improvement.

In some countries, there is already a legal market for blood plasma. In the wake of the BSE crisis of the 1990s, plasma donations are not used in the UK. But in the US, donors can make $200 a month (plus loyalty points) from plasma donations. The fresh plasma is separated from the blood, and the red blood cells returned to the bloodstream, in a sitting that lasts 90 minutes. The plasma is used in medical procedures, to treat coagulation disorders and immune deficiencies. The business is completely legitimate, but if young blood rejuvenates our cells is proved to have anti-ageing effects, the risk of backstreet operators setting up will soar. When I asked Wyss-Coray if the prospect worried him, he looked serious. “Absolutely,” he said. “There are always going to be nutcases.”

These are worst-case scenarios. The Stanford trial may find that simply injecting young plasma into old people has little or no effect. Wyss-Coray confesses that he suspects as much. He believes that rejuvenating older people might take a more potent brew than natural plasma. He has in mind a concentrated blend of 10 or 20 pro-youthful factors from young blood, mixed with antibodies that neutralise the effects of ageing factors found in old blood.

“As we get older, we have fewer stem cells and newly born neurons in our brains, and our learning and memory are affected,” says Villeda. “It’s not ddementia it’s just the natural degeneration associated with age.”

 

Amy Wagers emphasizes that no one has convincingly shown that young blood lengthens lives, and there is no promise that it will. Still, she says that young blood, or factors from it, may hold promise for helping elderly people to heal after surgery, or treating diseases of ageing.

Young mice blood has been studied to cause repair of age related damage such as cardiac hypertrophy, muscle dysfunction, demyelination processes and brain vasculature system in old mice. The mouse is the most common model organism for preclinical studies even though it has not proven particularly reliable at predicting the outcome of studies in humans.

Wyss-Coray one of the authors of the study mentioned in the question is a part of board of directors of a biotechnology start-up named Alkahest to explore the therapeutic implications of the mice findings in humans. The young mice blood treatment has been shown to have effects in old mice neural dysfunctions such as

1. Cardiac hypertrophy: Loffredo et.al. have concluded that treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging in 2013.

2. Muscle dysfunction: GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction per conclusions of Sinha M et.al. in 2014.

3. Reversal of demyelination processes: Ruckh JM et.al. in 2012 concluded that enhanced remyelinating (Remyelination is a term for the re-generation of the nerve’s myelin sheath, damaged in many diseases) activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.

4. Improvement of brain vasculature system: Katsimpardi L et.al. in 2014 concluded that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. Studies in mice and Xenopus suggest that this protein is involved in mesodermal formation and neurogenesis during embryonic development. Research shows that there could be multiple forms of GDF11

Sources:

http://www.nature.com/news/ageing-research-blood-to-blood-1.16762

http://randolab.stanford.edu/

http://glennlaboratories.stanford.edu/

http://www.nature.com/news/blood-hormone-restores-youthful-hearts-to-old-mice-1.12971

http://www.bizjournals.com/sanfrancisco/print-edition/2014/01/31/conboy-uc-berkeley-aging-research.html

http://www.bizjournals.com/sanfrancisco/blog/biotech/2014/05/young-blood-stanford-researchers-hope-plasma.html

http://www.bizjournals.com/sanfrancisco/print-edition/2014/01/31/aging-calico-levinson-buck-institute.html

http://www.nytimes.com/2014/05/05/science/young-blood-may-hold-key-to-reversing-aging.html?_r=0

https://www.ucsf.edu/news/2014/01/122211/blood-work-scientists-uncover-surprising-new-tools-rejuvenate-brain

https://www.newscientist.com/article/mg22329831-400-young-blood-to-be-used-in-ultimate-rejuvenation-trial/

http://www.theguardian.com/science/2015/aug/04/can-we-reverse-ageing-process-young-blood-older-people

 

PD Dr. med. Rainer Arendt
FMH Cardiology, Internal Medicine
Regenerative Medicine 

SWISS  PREVENTION  CLINIC
Klausstrasse 10
CH-8008 ZURICH
T +41 43 336 7260
M +41 78 825 0803
F +41 43 336 7261

rainer.arendt@swisspreventionclinic.ch

www.swisspreventionclinic.ch
www.patientcircle.org

Thursday
Jul072016

Can we reverse the ageing process by putting young blood into older people?

A series of experiments has produced incredible results by giving young blood to old mice. Now the findings are being tested on humans. Ian Sample meets the scientists whose research could transform our lives

On an August morning in 2008, Tony Wyss-Coray sat in a conference room at the Veterans Affairs hospital in Palo Alto, California, waiting for his lab’s weekly meeting to begin. Wyss-Coray, a professor of neurology at Stanford University, was leading a young group of researchers who studied ageing and neurodegeneration. As a rule, the gatherings were forgettable affairs – the incremental nature of scientific progress does not lend itself to big surprises. But a lab member scheduled to speak that day had taken on a radical project, and he had new results to share.

Saul Villeda, an ebullient PhD student with slick black hair and a goatee, had spent the past year engrossed in research that called to mind the speculative medical science of the middle ages. He was investigating whether the old and frail could be rejuvenated by infusions of blood from the young. The hypothesis was not as absurd as it might sound.

Villeda’s work took skill. A mouse brain is the size of a peanut. To remove one for inspection is not difficult, but Villeda then had to cut each brain into wafers 1/25th of a millimetre thick using a cryomicrotome, a machine that resembles a benchtop deli slicer. Villeda took multiple slivers from about 40 mice and then stained them with a dye that binds to newborn neurons. Under a microscope the baby brain cells stand out like little brown trees.

The day before the lab meeting, Villeda and his colleague Kurt Lucin arrived early for work. With a small paintbrush, Villeda swept each brain slice, one after another, onto a microscope slide, and counted the tiny brown tree shapes. It took hours: he had about 200 slivers to inspect, from old and young mice. After totting up the newborn neurons in each section, he tapped the number into a statistics program. He finished after 10pm.

Though it was late, Villeda made Lucin stay with him to crunch the numbers. “It had been such a long experiment. I thought, if it doesn’t work, he’s here. We can go and grab a drink,” Villeda told me recently. He clicked a button on the screen marked “analyse”. The statistics program took all the data and calculated the average number of newborn neurons in the brains of each group of mice. A moment later, bar charts popped up on the screen.

Villeda got three hours’ sleep that night. The next morning, he stood up at the lab meeting and revealed to his colleagues what young blood did to the ageing brain. “There was a palpable electricity in the room,” Wyss-Coray recalled. “I remember seeing the images for the first time and saying, ‘Wow.’” Old mice that received young blood experienced a burst of brain cell growth in the hippocampus. They had three to four times as many newborn neurons as their counterparts. But that was not all: old blood had the opposite effect on the brains of young mice, stalling the birth of new neurons and leaving them looking old before their time.

 

Old mice that received young blood experienced a burst of brain cell growth in the hippocampus

 

The other scientists in the room were stunned. Some were sceptical. Could it be real? “This could be big,” said Wyss-Coray. “If an old mouse starts to make more neurons when you give it young blood? That is amazing.”

Since that meeting seven years ago, research on this topic has moved on dramatically. It has led some to speculate that in young blood might lie an antidote to the ravages of old age. But the apparent rejuvenating properties of young blood must be treated with healthy scepticism. The hopes they raise rest solely on mouse studies. No beneficial effects have ever been proven in humans. Then again, no one has ever looked.

That is about to change. In October 2014, Wyss-Coray launched the first human trial of young blood. At Stanford School of Medicine, infusions of blood plasma from young people are being given to older people with Alzheimer’s disease. The results are expected at the end of the year. It is the greatest test yet for the medical potential of young blood.

* * *

For much of history, people sought to halt ageing to achieve immortality – or at least to live for hundreds of years. These days, scientists tend to have more modest aims. In wealthy nations, basic healthcare and medical advances have driven up lifespan for the past century. Five years from now, for the first time in human history, there will be more over-60s than children under five years old. In 2050, two billion people will be 60 or older, nearly double the number today.

Behind that statistic lies a serious problem. People are living longer, but they are not necessarily living better. The old struggle with chronic conditions, often many at once: cancer, respiratory disease, heart disease, diabetes, arthritis, osteoporosis, dementia.

Blood plasma.

 

 

In the first human trial of the effects of young blood, at Stanford University, infusions of blood plasma from young people are being given to older people. Photograph: Ralf Hirschberger/dpa/Corbis

Medical researchers tend to tackle these diseases separately. After all, the illnesses are distinct: cancer arises from mutated DNA; heart disease from clogged up blood vessels; dementia from damaged brain cells. The biological processes that underpin the pathologies vary enormously. Each, then, needs its own treatment. Yet some researchers take another view: the greatest driver of disease in old age is old age itself. So why not invent treatments for ageing?

The idea has caught on, though it is still far from mainstream. Google’s secretive Calico operation, founded in 2013, is putting hundreds of millions of dollars into anti-ageing researchCraig Venter, the genetics entrepreneur, has launched a company called Human Longevity to find the genes that lead to long life. Meanwhile, scientists have asked the US Food and Drug Administration to approve trials of well-known drugs, such as the diabetes treatment, metformin, in the hope of uncovering anti-ageing effects.

 

People are living longer, but they are not necessarily living better. The old struggle with chronic conditions

 

Scientists may never halt the process entirely: ageing is an opaque and complex mingle of molecular pathways. But they might learn how to stop changes that underpin the worst chronic diseases. They want to extend healthspan, not lifespan. The stakes are enormous. Over the next decade, the cost of dementia care in Britain alone will rise to £24bn, a 60% increase on the cost in 2007. Last year, the World Health Organisation called the rise in chronic illness due to the greying population a major public health challenge.

Wyss-Coray is not the first person to wonder whether the answer to the problem of ageing might lie in human blood. One of the first physicians to propose blood transfusions to rejuvenate older people was Andreas Libavius, a German doctor and alchemist. In 1615 he proposed connecting the arteries of an old man to those of a young man. He had high hopes for the procedure. “The hot and spirituous blood of the young man will pour into the old one as if it were from a fountain of youth, and all of his weakness will be dispelled,” he claimed, in an account told in the Textbook of Bloodbanking and Transfusion Medicine by Sally Rudmann. It is unclear how it turned out; there is no record of the transfusion happening.

 

The fledgling years of the Royal Society, founded in London in 1660, witnessed some of the earliest experiments in blood transfusion. When Robert Boyle, one of the society’s founders, compiled a wishlist of scientific projects, the top entry was “The prolongation of life”. That might be achieved, he hoped, by replacing old blood with new.

Progress in science takes more than hope. With no knowledge of blood groups or coagulation factors, the early transfusion experiments were deadly. Before long, the procedure was banned, first in France, and then England. The pope endorsed the bans in 1679, and transfusion all but ceased for a century. When advances in medicine allowed its return, the emphasis was on healing the sick, not helping the aged.

It is 400 years since Libavius proposed that young blood could rejuvenate older people. At the time, the idea was radical and dangerous. Even though modern science has made blood transfusions safe, blood remains a mysterious fluid: it ferries more than 700 proteins and other substances around our bodies; many are known, but what they do is less clear. Wyss-Coray suspects that among them are factors that orchestrate the ageing process. If scientists can understand how they work, the ageing process might be laid bare. It could be slowed down, or perhaps even reversed.

* * *

When Wyss-Coray was in his 20s and 30s, he did not much care about ageing. “You have no understanding of what the problems are,” he recently told me, in his soft Swiss-German accent. Sitting in his office at the Veterans Affairs hospital, surrounded by books on immunology and biology, Wyss-Coray was fashionably unshaven, with a crop of blonde hair and lively blue eyes framed by dark rimmed glasses. “Now I see that the brain starts to slow down. I’m not as quick any more at grasping things, or remembering faces. I used to see a person for a few minutes and I’d remember their face. I couldn’t understand how they’d not remember who I was. And now it happens to me. It annoys the crap out of me.”

For Wyss-Coray, ageing has become much more than a personal bugbear. In 2014, the prestigious US journal, Science, named his work on young blood one of its breakthroughs of the year. He is regularly invited to give talks at conferences and the world’s top universities; in January, he spoke at the World Economic Forum in Davos. “In almost every talk I give, people make comments or jokes about vampires.” He slumped back in his chair and groaned. Another question also crops up: “I have people asking me, ‘Are you taking young blood?’” He assured me that he was not, and screwed up his face in horror, but it’s easy to see why they ask; he looks much younger than his 50 years.

Tony Wyss-Coray.

 Tony Wyss-Coray is a professor of neurology at Stanford university Photograph: Tony Wyss-Coray

Wyss-Coray was the first in his family to go to university. From the start, he set his sights on a career in the US. In 1993, he began as a postdoctoral fellow at the well-regarded Scripps Research Institute in La Jolla, California, studying HIV-related dementia. The work led to Alzheimer’s research, focusing on how the immune system played a role in the disease. In 2002, he joined Stanford University’s medical school, where he remains a faculty member.

Much of Wyss-Coray’s research on Alzheimer’s used mice that were genetically modified to develop the disease. This kind of experimentation has major limitations. Alzheimer’s mice mimic the forms of disease that run in families because of specific mutations, but they cannot tell us much about the origins of the sporadic forms of Alzheimer’s, which account for 99% of human cases. “People always joke: if you’re a mouse and you have Alzheimer’s, we can cure you, no problem,” Wyss-Coray told me. For humans, however, nothing so far has worked.

Frustrated by the limitations of his experiments, Wyss-Coray looked for better ways to understand how the disease first arose in humans. Brain scans and cognitive tests were out – neither revealed anything about disease at the molecular level. Nor would it make sense to study the brains of the dead, as scientists had traditionally done: the subtle neurological changes that lead to Alzheimer’s are set in motion two or three decades before patients are diagnosed, which meant old brains told you how bad the rot got, but not how the rot got started.

Wyss-Coray wondered if blood might hold the answer. Human blood travels 96,000 kilometres along the arteries, veins and capillaries of the circulatory system. It circulates through every organ. What if blood picked up information as it streamed around the body? What if its molecular makeup reflected the state of the brain, as it aged and changed with disease?

He assembled an international team of two dozen scientists to test the idea. They analysed blood plasma from more than 200 Alzheimer’s patients, and compared the profiles with those from healthy people. The findings, published in 2007, made headlines around the world. By measuring the levels of certain proteins in plasma, Wyss-Coray’s team believed they had found an accurate way to diagnose Alzheimer’s years before it began to take its toll. Wyss-Coray set up Satoris, a private company, to commercialise the research.

The study was too good to be true. Wyss-Coray’s later efforts to develop the test showed it was unreliable. In the course of this work, however, he had come across something intriguing. He noticed that in healthy people, the levels of certain proteins in blood fell with age. By 20 years old, most had already dropped steeply. Meanwhile, the levels of other proteins ramped up. Some doubled or tripled in old age. What the changes meant, no one knew.

* * *

One floor up from Wyss-Coray’s lab is the office of Thomas Rando, a neurologist and deputy director of the Stanford Center on Longevity. On his desk sits a small display of chemistry lab glassware and dozens of miniature figurines of the New York Giants. It was Rando who hired Wyss-Coray in 2002. “Tony is incredibly creative,” Rando told me. “He thinks about neuroscience in the context of the whole organism, as opposed to someone who has tunnel vision of the brain.”

In 2005, Rando oversaw a series of important experiments that would become closely intertwined with Wyss-Coray’s work. The question Rando wanted to investigate centred on stem cells. The body’s tissues need stem cells to remain healthy and in good working order, but in older people, stem cells stop doing their job – this is why wounds heal so much slower as we age. Rando wondered whether stem cells failed in old animals because they no longer got the right signals. What if something in young blood turned them back on again? Perhaps he could make older people heal as fast as young ones.

Rando’s experiments involved an unsettling but remarkable procedure in which mice were cut along the flanks and sewn together, wound-on-wound. This procedure, pioneered by the 19th-century French physiologist Paul Bert, is known as parabiosis. Bert’s work on conjoined rats demonstrated that, once their wounds had healed, the animals developed a single, shared circulatory system.

For a long time, experiments involving parabiosis were gruesome. In 1956, Clive McCay, an American gerontologist at Cornell University who was pursuing a similar line of research to Wyss-Coray, described his own attempts to conjoin rats in the Bulletin of the New York Academy of Medicine. “If the two rats are not adjusted to each other,” he wrote, “one will chew the head of the other until it is destroyed.” Grim though it was, McCay’s work hinted that young blood might have rejuvenating properties.

Though other scientists took up McCay’s experiments and got similarly encouraging results, the work was effectively abandoned in the 1970s. Not knowing what to make of their findings, researchers moved on to other projects. Only when parabiosis was resurrected at Stanford did scientists start to make sense of the anti-ageing effects.

 

Parabiosis is different today: ethics committees are strict and the surgical procedure has improved. The animals are genetically matched, so there is no risk of immune rejection. Once they have recovered from the operation, paired animals tend to eat normally and to make nests together. But the procedure is still disturbing – it would be a stretch to call the animals happy.

Scientists in Rando’s lab joined old and young mice for five weeks and looked at how well they repaired little tears in muscle tissue. The young blood activated stem cells in the old mice that swiftly regenerated their damaged muscles. The young mice, however, fared worse for their exposure to old blood. Their stem cells became sluggish, and their tissues healed more slowly. Rando saw hints of another effect too, but needed more evidence before he could publish: the old mice had begun to grow new brain cells.

The results led Wyss-Coray and Rando to collaborate. The kinds of proteins Wyss-Coray had seen rise and fall in blood were known to have effects on biological processes. What if they had driven the changes Rando had seen in muscle? Might they similarly revitalise the brain? Rather than being mere signatures of age, the proteins might be chemical cues for the ageing process itself.

Saul Villeda

 

 

Saul Villeda carried out the early research on the restorative properties of young blood. Photograph: Saul Villeda

Wyss-Coray asked his PhD student Saul Villeda to investigate. Villeda grew up in Pasadena on the outskirts of Los Angeles. His parents had immigrated illegally from Guatemala in the 1970s, and took jobs in factories, or as janitors. They became legal residents when Saul was a boy. Villeda had not planned on being a scientist when he went to college at the University of California in LA. But he enjoyed physiology classes: “I instantly fell in love with research,” he told me. “The idea that you were investigating something completely new and that you could come up with your own experiments to figure things out was amazing.” When he told his parents he wanted to be a university scientist, they didn’t really know what he meant. “I took them to my undergraduate lab to show them what a scientist looked like,” he said. “I think that really helped them understand.”

After Villeda presented his work on conjoined mice to Wyss-Coray at the lab meeting in August 2008, he went on to look at proteins in old and young blood. He found that the old mice, like old humans, had high levels of a protein called CCL11 in their blood. If you injected CCL11 into young mice, their learning and memory declined. The protein hampered the growth of new neurons. The young mice struggled to remember the location of a hidden platform in a water maze, and took longer to recognise a place where they had received a small but unpleasant electric shock. Villeda published the landmark research in 2011.

But the study failed to answer a major question: could proteins in young blood restore the mental capacities that old animals lost? Testing this was by no means easy. A mouse’s wits can be examined in a water maze, but two mice sewn together? It would be impossible to know how much one had led the other. Wyss-Coray believed that rather than experimenting with conjoined mice, the only option was to take blood from young mice, strip out the blood cells, and inject the plasma into old ones. This, too, was difficult. One mouse yields about 200 microlitres of plasma, the yellowish fluid that contains all the proteins. That is enough for two injections into another mouse. For an experiment that requires 10 injections into 10 old mice, you need to siphon the blood from 50 young mice.

Villeda was reluctant to do the experiment. He didn’t think it would work. But he changed his mind when he performed electrical measurements on slices of brain tissue and found that exposure to young blood strengthened the connections between neurons that had weakened in old mice. He went ahead with the plasma injections. Each mouse had one injection every three days for 24 days. The plasma came from three-month-old mice, the equivalent of human beings in their 20s, and went into 18-month-old mice, the equivalent of a human in their 60s.

The results were dramatic. Old mice given young plasma jabs aced the water-maze test, and quickly remembered the cage where they had earlier received an electric shock. They performed like mice half their age. “That time, I showed Tony the data one-on-one,” Villeda told me. “I was freaking out. I said: ‘I have to see this again.’”

Not everyone was impressed. The journal Nature rejected the study in 2012; its reviewers felt the work was not a big enough leap forward. So Wyss-Coray and Villeda sent it along to a sister publication, Nature Medicine. The editors there wanted to know precisely how young blood helped old mice. Villeda, who had just opened his own lab at the University of California in San Francisco, said he would find out.

A microscopic view of a plasma cell inside a blood vessel.

 

A microscopic view of a plasma cell inside a blood vessel. Photograph: Alamy

Villeda looked at how young blood altered the way genes are expressed in old mice. He noticed a stark difference among genes that help neural connections strengthen and weaken, a process crucial for learning and memory. In normal ageing, the genes that control this “synaptic plasticity” become less active. Young plasma jabs ramped the gene activity back up again.

From the pattern of genes affected, Villeda traced the mechanism back to a master regulator in the brain, a protein known as CREB, which behaves like a switch that turns on many genes at once, and is instrumental in memory and learning from birth. To confirm young plasma was working through CREB, Villeda’s PhD student Kristopher Plambeck designed a virus that turned the master regulator off. When they injected the virus into old mice, young plasma had a much reduced effect on their brains. The animals performed better, but only slightly. It showed that young plasma worked through CREB, though not exclusively.

The study was published in Nature Medicine in 2014. Immediately, emails flooded in to Wyss-Coray’s inbox. Alzheimer’s patients wanted infusions of young blood. So did numerous aged billionaires. One, who flies around in a jet with his name emblazoned on the side, invited Wyss-Coray to an Oscars after-party this year. (He didn’t go.) Another correspondent wrote with a more disturbing offer: he said he could provide blood from children of whatever age the scientists required. Wyss-Coray was appalled. “That was creepy,” he said. 

Wyss-Coray and Villeda were not the only scientists making headway in this area. Two members of the team behind Rando’s 2005 paper on stem cells had moved to the University of California, Berkeley, where they found that oxytocin, often called the love hormone, rejuvenated old muscle tissue. Another, Amy Wagers, had begun working at Harvard. She showed that when given young plasma, old mice regained their stamina. On a treadmill, the treated mice ran for an hour on average, compared with only 35 minutes for untreated ones.

Wagers picked out one factor, known as GDF11, as a rejuvenating protein in young blood. In Villeda’s most recent paper, published in July 2015, he found a second factor, B2M, which peaks in the blood of old mice, as it does in old humans: when injected into young mice, B2M impairs their memories.

The studies all point in one direction. Among the hundreds of substances found in blood are proteins that keep tissues youthful, and proteins that make them more aged. Wyss-Coray has a hypothesis: when we are born, our blood is awash with proteins that help our tissues grow and heal. In adulthood, the levels of these proteins plummet. The tissues that secrete them might produce less because they get old and wear out, or the levels might be suppressed by an active genetic programme. Either way, as these pro-youthful proteins vanish from the blood, tissues around the body start to deteriorate. The body responds by releasing pro-inflammatory proteins, which build up in the blood, causing chronic inflammation that damages cells and accelerates ageing.

“This opens an entirely new field. It tells us that the age of an organism, or an organ like the brain, is not written in stone. It is malleable. You can move it in one direction or the other,” says Wyss-Coray. “It’s almost mythological that something in young organisms can maintain youthfulness, and it’s probably true.”

* * *

As a business proposition, the transfusion of young blood raises all kinds of fears. It raises the spectre of a macabre black market, where teenagers bleed for the highest bidder, and young children go missing from the streets. Then there is the danger of unscrupulous dealers selling fake plasma, or plasma unsafe for human infusion. The fears are not unfounded: health has become one of the most lucrative sectors for criminals and con artists.

Havocscope, an online database, tracks the latest prices of all manner of black market goods and services. For $600 you can buy an AK-47 in Europe. A rhino-horn dagger will cost you $14,000. The services of a group of former military snipers? That will be $800,000. The list includes human organs too, mostly lungs, kidneys and livers. Today, a healthy seller can expect about $5,000 for their kidney. The organ broker who handles the deal can make a hefty profit, selling it on for $150,000 to a wealthy patient who needs a transplant.

In some countries, there is already a legal market for blood plasma. In the wake of the BSE crisis of the 1990s, plasma donations are not used in the UK. But in the US, donors can make $200 a month (plus loyalty points) from plasma donations. The fresh plasma is separated from the blood, and the red blood cells returned to the bloodstream, in a sitting that lasts 90 minutes. The plasma is used in medical procedures, to treat coagulation disorders and immune deficiencies. The business is completely legitimate, but if young plasma is proved to have anti-ageing effects, the risk of backstreet operators setting up will soar. When I asked Wyss-Coray if the prospect worried him, he looked serious. “Absolutely,” he said. “There are always going to be nutcases.”

 

The transfusion of young blood raises the spectre of a macabre black market where teenagers bleed for the highest bidder

 

These are worst-case scenarios. The Stanford trial may find that simply injecting young plasma into old people has little or no effect. Wyss-Coray confesses that he suspects as much. He believes that rejuvenating older people might take a more potent brew than natural plasma. He has in mind a concentrated blend of 10 or 20 pro-youthful factors from young blood, mixed with antibodies that neutralise the effects of ageing factors found in old blood.

In January 2014, Wyss-Coray set up Alkahest, a company that aims to separate plasma into its constituent parts, and combine them into a potent, rejuvenating cocktail. In Silicon Valley, scientists frequently launch start-up companies on the back of early-stage research – an alignment of the commercial and the scientific that some researchers still frown upon.  Sergio Della Sala, a professor of human cognitive neuroscience at the University of Edinburgh, warns that creating a business before the science is done can raise a conflict of interest. “Science should first understand then sell,” he said. “We should always be skeptical when these two factors are reversed.”

Wyss-Coray formed Alkahest with Karoly Nikolich, an entrepreneur and neuroscientist at Stanford, who immigrated to the US from Hungary in the 1970s. I met Nikolich at his office in Menlo Park in February. He has thin hair, a full grey moustache and a mind filled with stories. Sat at a table on the sun-drenched roof terrace, Nikolich, handed me an Alkahest business card. The company logo is a blue droplet. Inside it is a golden disc.

Karoly Nikolich.

 Karoly Nikolich, co-founder with Tony Wyss-Coray of Alkahest, the company trying to identify the key proteins in plasma that rejuvenate or age human tissues. Photograph: Karoly Nikolich

Nikolich got to know Wyss-Coray in 2005. He had taken on the job of executive director of the Neuroscience Institute at Stanford University and over the years, Nikolich kept tabs on Wyss-Coray’s progress – from the Alzheimer’s blood test to the rejuvenating properties of young blood. But it wasn’t until spring 2012 that plans to form a company emerged. Nikolich had flown to Hong Kong to visit the family of Chen Din-hwa, a Chinese billionaire known as the King of Cotton Yarn. Three years earlier, Chen had died, aged 89, with Alzheimer’s disease. His grandson told Nikolich that towards the end of his life, Chen barely recognised his own family. Then he had a plasma transfusion for an unrelated condition, which seemed to have a spectacular effect. His mind was clearer. He was suddenly cogent.

Nikolich told them about Wyss-Coray’s research and the potential for plasma-based therapies that revitalised the ageing brain. Before long, the conversation turned to starting a company. The family invested a year later. The money got Alkahest established and ready to launch the first human trial of young plasma.

Alkahest’s ultimate goal – to identify the key proteins in plasma that rejuvenate or age human tissues and then manufacture a product that uses them – could take 10 to 15 years. In the near term, the company has another strategy. Earlier this year, the Spanish blood products firm, Grifols, pledged $37.5m for a 45% stake in Alkahest. With another $12.5m, the company will bankroll more research in exchange for rights to Alkahest’s first products. Over the next two years, Alkahest will take human plasma and divide it into fractions that are rich in different proteins. Each fraction will then be tested in mice to see if they boost brain function. Any that do will be swiftly introduced into human trials and developed into the first generation of products.

And what then? One enormous obstacle for hopes of plasma therapy is the limited supply. In a rough extrapolation from the mouse studies, Nikolich estimates that the globe’s entire plasma supply would be sufficient for only half a million of the world’s 15 million Alzheimer’s patients. “That means big questions about who gets treatment and who does not,” he said.

* * *

A short drive from the Palo Alto Veterans Affairs hospital is Stanford University’s School of Medicine, where the Alkahest trial is running. The woman in charge of the trial is Sharon Sha, a specialist in behavioural neurology who spends much of her time with patients who have Alzheimer’s. When I visited in February, Sha, a cheery woman with dark shoulder-length hair, was running late for a meeting in her third-floor office. But she was delayed for good reason: she had been infusing young plasma into an Alzheimer’s patient enrolled on the trial – a procedure that cannot be rushed.

The Alkahest trial is small. Sha can enrol only 18 people aged 50 to 90 with mild to moderate Alzheimer’s disease. Each receives a unit of young human plasma or saline once a week for four weeks. They have the next six weeks off, then have four more weeks of infusions. Those who had plasma first time around get saline and vice versa. The process is blinded, so neither the patients, nor their carers, nor Sha herself, know who is receiving what. Throughout the trial, doctors will look for cognitive improvements. Only at the end of the trial, as soon as October this year, will Sha analyse the findings.

Sharon Sha.

 

Sharon Sha is in charge of the blood plasma trial at Stanford University’s School of Medicine. Photograph: Sharon Sha

Big questions lie ahead. Even if none of the patients benefit from young plasma, the research is far from finished. The plasma for the trial comes from donors under 30, and it may not be potent enough. The patients on the trial have dementia already, and may be too far gone to rescue.

Earlier this year, John Hardy of University College London, who is the most cited Alzheimer’s researcher in Britain, saw Wyss-Coray’s latest data at a meeting in London. “It’s really interesting work,” he told me. “It’s woken everybody up.” Nonetheless, Hardy is cautious; he suspects that young plasma will be less effective in people than in mice, because people live so much longer, and in far more varied environments. But, he said: “I would guess this will still point us towards pathways involved in ageing more generally.”

If patients improve with infusions of young plasma, scientists will be ecstatic. But the finding would need to be replicated, ideally at other hospitals, and in more patients, in order to convince researchers. If any benefits stand the test of time, the studies will move on, to tease out the best doses and ages at which to give plasma, how patients’ brains change, and whether improvements make a real difference to the life of someone who can no longer recognise their own family.

Then there is safety. Toying with the ageing process might backfire. Rando is concerned that pumping pro-youthful proteins into people for years could end up giving them cancer. Wyss-Coray agrees it is a worry, but points out that long-term growth hormone therapy appears to be safe. “We just don’t know yet whether or not it will be a problem,” he said.

Rando is more upbeat about infusing patients with pro-youthful proteins for short periods. An elderly person having surgery might get an infusion to help them heal like a teenager. “Let’s say it works. If you can target tissues and improve wound healing in older people, that would be a feasible approach. It would not be about making 90-year-olds younger, or having people live to 150. It’s about healthy living, not longer living,” he said.

In the 20 years that Wyss-Coray has lived in the US, his attitude to ageing has swung from disinterest to fascination. Why does a mouse live for three years and a human for 80? He sees its effects on a personal level too. He gets frustrated when a word fails to come as quickly as it once did, but knows how much worse it must be for people noticing the early signs of dementia: their words and memories slipping away into the gloom.

The carers of the patients enrolled in the young-blood trial keep journals to record how well the patients are doing. Among their pages may be signs of hope, that perhaps in the days after an infusion, a patient does a little bit better. “If it actually works? That would be huge. Every patient would want it,” Wyss-Coray said. He smiled. “I’d probably have to turn off my email and go somewhere else.”

 

PD Dr. med. Rainer Arendt
FMH Cardiology, Internal Medicine
Regenerative Medicine 

SWISS  PREVENTION  CLINIC
Klausstrasse 10
CH-8008 ZURICH
T +41 43 336 7260
M +41 78 825 0803
F +41 43 336 7261

rainer.arendt@swisspreventionclinic.ch

www.swisspreventionclinic.ch
www.patientcircle.org

 

Thursday
Jul072016

How young blood might reverse aging. Yes, really

Based on Tony Wyss-Coray’s TED lecture of Aug. 2015

 

 

The famous Fountain of Youth. If you drink its water or you bathe in it, you will get health and youth. Every culture, every civilization has dreamed of finding eternal youth. There are people like Alexander the Great or Ponce De León, the explorer, who spent much of their life chasing the Fountain of Youth. They didn't find it. But what if there was something to it? What if there was something to this Fountain of Youth?

I will share an absolutely amazing development in aging research that could revolutionize the way we think about aging and how we may treat age-related diseases in the future. It started with experiments that showed, in a recent number of studies about growing, that animals -- old mice -- that share a blood supply with young mice can get rejuvenated. What Tom Rando, a stem-cell researcher, reported in 2007, was that old muscle from a mouse can be rejuvenated if it's exposed to young blood through common circulation. This was reproduced by Amy Wagers at Harvard a few years later, and others then showed that similar rejuvenating effects could be observed in the pancreas, the liver and the heart. But what I'm most excited about, and several other labs as well, is that this may even apply to the brain.

So, what we found is that an old mouse exposed to a young environment in this model called parabiosis, shows a younger brain -- and a brain that functions better. And I repeat: an old mouse that gets young blood through shared circulation looks younger and functions younger in its brain. So when we get older -- we can look at different aspects of human cognition, and you can see on this slide here, we can look at reasoning, verbal ability and so forth. And up to around age 50 or 60, these functions are all intact, and as I look at the young audience here in the room, we're all still fine.

But it's scary to see how all these curves go south. And as we get older, diseases such as Alzheimer's and others may develop. We know that with age, the connections between neurons -- the way neurons talk to each other, the synapses -- they start to deteriorate; neurons die, the brain starts to shrink, and there's an increased susceptibility for these neurodegenerative diseases.

One big problem we have -- to try to understand how this really works at a very molecular mechanistic level -- is that we can't study the brains in detail, in living people. We can do cognitive tests, we can do imaging --all kinds of sophisticated testing. But we usually have to wait until the person dies to get the brain and look at how it really changed through age or in a disease. This is what neuropathologists do, for example. So, how about we think of the brain as being part of the larger organism. Could we potentially understand more about what happens in the brain at the molecular level if we see the brain as part of the entire body? So if the body ages or gets sick, does that affect the brain? And vice versa: as the brain gets older, does that influence the rest of the body? And what connects all the different tissues in the body is blood. Blood is the tissue that not only carries cells that transport oxygen, for example, the red blood cells, or fights infectious diseases, but it also carries messenger molecules, hormone-like factors that transport information from one cell to another, from one tissue to another, including the brain. So if we look at how the blood changes in disease or age, can we learn something about the brain? We know that as we get older, the blood changes as well, so these hormone-like factors change as we get older. And by and large, factors that we know are required for the development of tissues, for the maintenance of tissues -- they start to decrease as we get older, while factors involved in repair, in injury and in inflammation -- they increase as we get older.

So there's this unbalance of good and bad factors, if you will. And to illustrate what we can do potentially with that, I want to talk you through an experiment that we did. We had almost 300 blood samples from healthy human beings 20 to 89 years of age, and we measured over 100 of these communication factors, these hormone-like proteins that transport information between tissues. And what we noticed first is that between the youngest and the oldest group, about half the factors changed significantly. So our body lives in a very different environment as we get older, when it comes to these factors. And using statistical or bioinformatics programs, we could try to discover those factors that best predict age -- in a way, back-calculate the relative age of a person. And the way this looks is shown in this graph. So, on the one axis you see the actual age a person lived, the chronological age. So, how many years they lived.

And then we take these top factors that I showed you, and we calculate their relative age, their biological age. And what you see is that there is a pretty good correlation, so we can pretty well predict the relative age of a person. But what's really exciting are the outliers, as they so often are in life. You can see here, the person I highlighted with the green dot is about 70 years of age but seems to have a biological age, if what we're doing here is really true, of only about 45. So is this a person that actually looks much younger than their age? But more importantly: Is this a person who is maybe at a reduced risk to develop an age-related disease and will have a long life -- will live to 100 or more? On the other hand, the person here, highlighted with the red dot, is not even 40, but has a biological age of 65. Is this a person at an increased risk of developing an age-related disease? So in our lab, we're trying to understand these factors better, and many other groups are trying to understand, what are the true aging factors, and can we learn something about them to possibly predict age-related diseases?

So what I've shown you so far is simply correlational, right? You can just say, "Well, these factors change with age," but you don't really know if they do something about aging. So what I'm going to show you now is very remarkable and it suggests that these factors can actually modulate the age of a tissue. And that's where we come back to this model called parabiosis.

 

So, parabiosis is done in mice by surgically connecting the two mice together, and that leads then to a shared blood system, where we can now ask, "How does the old brain get influenced by exposure to the young blood?" And for this purpose, we use young mice that are an equivalency of 20-year-old people, and old mice that are roughly 65 years old in human years.

What we found is quite remarkable. We find there are more neural stem cells that make new neurons in these old brains. There's an increased activity of the synapses, the connections between neurons. There are more genes expressed that are known to be involved in the formation of new memories. And there's less of this bad inflammation. But we observed that there are no cells entering the brains of these animals. So when we connect them, there are actually no cells going into the old brain, in this model. Instead, we've reasoned, then, that it must be the soluble factors, so we could collect simply the soluble fraction of blood which is called plasma, and inject either young plasma or old plasma into these mice, and we could reproduce these rejuvenating effects, but what we could also do now is we could do memory tests with mice.

As mice get older, like us humans, they have memory problems. It's just harder to detect them, but I'll show you in a minute how we do that. But we wanted to take this one step further, one step closer to potentially being relevant to humans. What I'm showing you now are unpublished studies, where we used human plasma, young human plasma, and as a control, saline, and injected it into old mice, and asked, can we again rejuvenate these old mice? Can we make them smarter?

And to do this, we used a test. It's called a Barnes maze. This is a big table that has lots of holes in it, and there are guide marks around it, and there's a bright light, as on this stage here. The mice hate this and they try to escape, and find the single hole that you see pointed at with an arrow, where a tube is mounted underneath where they can escape and feel comfortable in a dark hole. So we teach them, over several days, to find this space on these cues in the space, and you can compare this for humans, to finding your car in a parking lot after a busy day of shopping.

So, let's look at an old mouse here. This is an old mouse that has memory problems, as you'll notice in a moment. It just looks into every hole, but it didn't form this spacial map that would remind it where it was in the previous trial or the last day. In stark contrast, this mouse here is a sibling of the same age, but it was treated with young human plasma for three weeks, with small injections every three days. And as you noticed, it almost looks around, "Where am I?" -- and then walks straight to that hole and escapes. So, it could remember where that hole was.

So by all means, this old mouse seems to be rejuvenated -- it functions more like a younger mouse. And it also suggests that there is something not only in young mouse plasma, but in young human plasma that has the capacity to help this old brain. So to summarize, we find the old mouse, and its brain in particular, are malleable. They're not set in stone; we can actually change them. It can be rejuvenated. Young blood factors can reverse aging, and what I didn't show you -- in this model, the young mouse actually suffers from exposure to the old. So there are old-blood factors that can accelerate aging. And most importantly, humans may have similar factors, because we can take young human blood and have a similar effect. Old human blood, I didn't show you, does not have this effect; it does not make the mice younger.

So, is this magic transferable to humans? We're running a small clinical study at Stanford, where we treat Alzheimer's patients with mild disease with a pint of plasma from young volunteers, 20-year-olds, and do this once a week for four weeks, and then we look at their brains with imaging. We test them cognitively, and we ask their caregivers for daily activities of living. What we hope is that there are some signs of improvement from this treatment. And if that's the case, that could give us hope that what I showed you works in mice might also work in humans.

Now, I don't think we will live forever. But maybe we discovered that the Fountain of Youth is actually within us, and it has just dried out. And if we can turn it back on a little bit, maybe we can find the factors that are mediating these effects, we can produce these factors synthetically and we can treat diseases of aging, such as Alzheimer's disease or other dementias.



PD Dr. med. Rainer Arendt
FMH Cardiology, Internal Medicine
Regenerative Medicine 

SWISS  PREVENTION  CLINIC
Klausstrasse 10
CH-8008 ZURICH
T +41 43 336 7260
M +41 78 825 0803
F +41 43 336 7261

rainer.arendt@swisspreventionclinic.ch

www.swisspreventionclinic.ch
www.patientcircle.org

Tuesday
Jan122016

GOOD HEALTH, REJUVENATION AND LIFESPAN EXTENSION IN  SWITZERLAND

Novel Program 2016

 

PD Dr. med. Rainer Arendt
FMH Cardiology, Internal Medicine
Regenerative Medicine 

SWISS  PREVENTION  CLINIC
Klausstrasse 10
CH-8008 ZURICH
T +41 43 336 7260
M +41 78 825 0803
F +41 43 336 7261

rainer.arendt@swisspreventionclinic.ch

www.swisspreventionclinic.ch
www.patientcircle.org

The Dolder Grand Health & Aesthetic Link 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

LIFESPAN  EXTENSION

 

  • Already today it is possible to increase the telomere length of the chromosomes, translating into an extension of human lifespan by approximately 10 years, by prudent eating, regular exercise, stress relief, regular chelation/detox treatment and especially by epigenetic rejuvenation, i.e. the gut, skin and vaginal microbiome exchange (the Élie Metchnikoff cure), with additional benefits for wellbeing, performance, fertility, increased vitality, and prevention of disease / neurodegeneration / hormonal involution (degeneration) later in life.
  • Recent scientific successes in rejuvenation, extending the lifespan, and discovery of a variety of species (including humans of advanced ages) having negligible senescence (decay due to old age), allow us to cancel accelerated or premature ageing for younger humans, reverse ageing or at least significantly delay it for older humans.
  • Our aim is to extend the lifespan in good health and full vitality

 

EPIGENETICS  AND  MICROBIOME

 

  • Epigenetics is the study, in the field of genetics, of cellular and physiological phenotypic trait variations, caused by external or environmental factors, mainly by the biofilms on our skin, in our mouth, in our lungs, in our gut, in our vagina, placenta and sexual organs,  that switch genes on and off and affect how cells read genes
  • The microbiota or microbiome is the community of commensal, symbiotic microbes that share our body space, or in a stricter sense stick to external or internal body surfaces as a biofilm
  • The microbiome and the human host emerged as a unity along evolution by a process of integration
  • The human microbiome has a significant impact on human development (before birth via the biofilm on the placenta), health and well-being
  • It is the rich array of beneficial microbes in our intestines and in our biofilms that makes us the human beings we are, preserves our health, and determines our lifespan.

 

 

MICROBIOME AND BIOFILMS

 

  • The importance of the commensal microbiota that colonizes the skin, gut, vaginal, placental, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome
  • The human body consists of more than 90% of microbial cells. The gastrointestinal tract harbors trillions of beneficial microorganisms that influence the development and homeostasis of the host. Alterations in composition and function of the microbiota have been implicated in a multitude of metabolic and inflammatory diseases in humans
  • There is a burgeoning scientific field on the role of the human microbiome in ageing, age-related diseases, diabetes, obesity, atherosclerotic diseases,  allergic diseases, autoimmune diseases, neuropsychiatric illnesses, infections, inflammatory bowel disease, and cancer

 

Mayo Clin Proc. 2014;89(1):107-114

Current Opinion in Immunology 2014, 30:54–62

Best Practice & Research Clinical Gastroenterology 27 (2013) 127–137

 

MEASUREMENT OF LIFESPAN

 

  • The chromosomes contain almost all of a cell’s genes. The tips of every chromosome are called the telomeres, they protect the chromosome from damage
  • Each time a cell divides, a little bit of the telomere is lost (therefore, the telomeres are regarded as our biological clock). When the telomeres become very short, the cell can no longer divide and dies
  • Genetic and epigenetic factors, the interaction of the immune and hormonal systems with our microbiota, influence how quickly the telomeres shorten
  • Restauration of the youthful diversity of the human  microbiota, healthy eating styles, increased fitness, stress relief result in longer telomeres reflecting/causing extensions of our lifespan
  • We measure the length of the telomeres in a blood sample as a parameter of lifespan before and after treatment

 

 

 

GENIUS LOCI

Switzerland –the prime destination for health, vitality, rejuvenation and long life 

Since the early 18th century, Switzerland - along with Italy – began to be perceived by the contemporaries as the most beautiful landscapes in Europe. Ever since, it has been regarded a fountain of health, long before the first patients with tuberculosis were sent for the famous sun, air and mountain cures in the early 20th century.  

 

And especially today, Switzerland is a  frontrunner in medical technology, with a healthcare system rightfully acknowledged to be one of the best in the world, with its exceptional quality of care and the excellence of its medical facilities.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

University Hospital, main buildings of the University and the ETH, and the city of Zurich, Switzerland 

 

GOALS OF REGENERATIVE MEDICINE

 

  • Ruling out treatable disease (by a comprehensive checkup examination, imaging, endoscopy, laboratory medicine)
  • Treating treatable disease, alleviating non-treatable disease (based on academic medicine and amended by the newest treatments from cellular, biological medicine, nutrition sciences, sports physiology, lifestyle medicine and neurosciences)
  • Extending the lifespan by restauration of the youthful diversity of our biofilms nIncreasing one’s resources and living well: staying quick-witted, social and sexual
  • Sidestepping risk factors for disease (preventive medicine, cardio-vascular prevention, lifestyle changes, exchanging non-beneficial microbes, neuroprotection)
  • Improving neurofunction, cardiac function by restauration of the gut-brain axis, of the gut-heart axis
  • Restauration of the senescent immune system, prevention of cancer
  • Regeneration of our endocrine (hormonal) systems

 

TYPICAL INDICATIONS FOR REGENERATIVE MEDICINE

 

  • Prevention or treatment of accelerated arteriosclerosis of carotid or coronary arteries (stroke, heart attack or sudden cardiac death)
  • Prevention or treatment of metabolic disease, type 2 diabetes, obesity
  • Prevention or treatment of autoimmune disease (multiple sclerosis, rheumatoid arthritis, thyroiditis, type 1 diabetes, psoriasis, auto-immune hepatitis)
  • Prevention or treatment of neuro-degenerative disease (dementia, Alzheimer, Parkinson, depression, autism, rare and devastating neurological disease)
  • Prevention or treatment of eating disorders (anorexia nervosa, binge eating, bulimia nervosa)
  • Prevention or treatment of inflammatory diseases (colitis, allergies, eczema, chronic lung disease)
  • Rehabilitation following cancer treatment, restauration of the immune system
  • Infertility, improvement of reproductive health, prevention of pregnancy complications
  • Early menopause, hormonal involution, loss of libido, painful sexual intercourse, erectile dysfunction
  • Lifespan extension, improvement in vitality, male performance, female wellbeing

 

 

 

CASE REPORTS IN REGENERATIVE MEDICINE

 

  • A 46 years old successful entrepreneur from Russia’s pacific coast, with alcohol dependency and depression, his fiancée requested him to undergo treatment before marriage. Following six gut microbiome transfers from a completely alcohol- and drug-free merry donor, he has been clear of alcohol for one year, and was able to resume “social” drinking of one to two glasses of wine only for dinner during his 2nd “sober year”. His mood is stable, work and social performance is no longer endangered.  By now the wedding has taken place and the marriage is harmonious.
  • A 61 years old housewife and society lady from Kazan with diffuse hair loss that is unresponsive to medical therapy, undergoes three microbiome exchange treatments, she is pleased with fuller hair and smoother skin six months later, therefore, doesn’t avoid public events anymore, and resumes her roles in beneficence.
  • A gifted 18 years young Australian student with polycystic ovary syndrome, menstrual abnormality, weight gain, acne, virilisation and severe reactive depression with indigestion and obstipation, undergoes three gut microbiome exchange treatments and is started on a combination oral contraceptive. She loses 12kg within 12 months, her skin clears, and virilisation is reversed, bowel movements normalised, she has become again a popular and outgoing young lady.
  • A 43 years old Chinese entrepreneur with premature menopause undergoes three gut and vaginal microbiome exchange treatments, her menstrual cycle has resumed and is regular three months later. There are no more hot flushes. Sexual intercourse is no more painful.
  • A 62 years old politician from Indonesia presents for general rejuvenation treatment, two months after three microbiome exchange treatments, his friends notice a “miraculously” improved golf swing that is now “silky smooth”. His exercise tolerance and oxygen uptake improved, and the telomere length increased from 6178 pb, i.e. second lowest quartile, to 6408 pb, i.e. second highest quartile of the normal range, reflecting an increase in lifespan.
  • A 26 years old Stanford creative writing student with long standing and recurrent inflammatory disease of unknown cause with constitutional complaints, musculo-skeletal symptoms, long confinement to bed, recurrent diarrhea undergoes three microbiome exchange treatments, almost a year later she has resumed her studies without limitations and had almost forgotten that she ever had been handicapped before. 
  • A 29 years old business student from Indonesia, got involved in a robbery incident, and suffered cerebral trauma when pushed from his motorcycle, with two weeks in coma. Recovery after the hospital stay had not been complete, due to cognitive impairment, slowed speech, double vision, decreased performance, anxiety, depression and impaired self esteem with consequent increase in body weight and loss in former interests. Following six microbiome exchange treatments and six months later, he has resumed working out twice per week with his personal trainer, restored his social relations and former popularity. He feels confident enough now to apply for a job.
  • A 22 years old model from Columbia, suffering from recurrent abdominal pain, and constipation following abdominal surgery for malrotation in childhood, becomes completely asymptomatic two months following microbiome exchange treatments.

 

RESTAURATION OF A HEALTHY GUT MICROBIOME


 

GUT-HEART AXIS:  RESTAURATION OF THE MICROBIOME APPEARS TO HAVE ANTI-ARTERIOSCLEROTIC EFFECTS

REGENERATIVE MEDICINE PROGRAMS

 

  • We offer novel treatment programs in regenerative medicine at The Dolder Grand Health & Aesthetic Link practice, in cooperation with Double Check Swiss Academic Center Zurich and leading Swiss medical institutions, both private and University-associated
  • Stand out among your peers, come for measurable and lasting health benefits, fresh looks and vitality
  • Look and feel younger than your age
  • Increase wellbeing, prowess and physical magnetism
  • For hormonal renewal and lifespan extension (telomere length ↑)
  • For improved overall health and metabolism (blood lipids↓ & sugar ↓)
  • For prevention or treatment of difficult-to-treat ailments, accelerated aging, auto-immune disease, inflammatory disease, degenerative diseases of the nervous system, depression, anorexia nervosa, bulimia nervosa, diabetes, obesity, and heart disease (coronary artery disease, heart failure)

 

MICROBIOME-BASED THERAPIES

 

  • This program provides support for the application of microbiome-based regenerative therapy  in a controlled and safe setting. All accompanying state-of-the-art diagnostic and therapeutic measures including checkup examinations are provided by the Double Check Center in Zurich (www.doublecheck.ch). Basis of this program is a general health program, duration one to seven days.
  • Day 0:  Check-in at your hotel or clinic, first consultation, program set-up
  • Day 1: Somatic checkup (at Double Check)
  • Double Check examination, depending on the patient’s preferences and needs (Executive / Executive plus, Individual)
  • Comprehensive laboratory testing, toxicology screening
  • Biological age (as measured by telomere length)
  • Further diagnostics, imaging, endoscopy if needed and desired
  • Day 1-3: Choices of regenerative medicine therapies
  • Day 2-7: Choices of personal training and enhancement
  • Day 1-7: Final assessment  with PD Dr. R. Arendt, hand-out of medical report with recommendations and prescriptions

 

Our donors are the most active, enthusiastic and blissful young people

 

LATEST  RESULTS  FROM  MICROBIOME  RESEARCH

 

CONSULTATIONS

 

  • A Double Check Executive Checkup  
    Alternative: Executive Plus Checkup 
  • Additional laboratory (hormones, xenobiotic metals, toxins)
  • Genetic assessment  of life span (telomere length)
  • Micro RNA extracts
  •    8 I.M. injections for repair   
  •    12 I.M. injections for repair
  • Gut microbiome exchange
        for 3 treatments
        for 5 treatments
  • Face rejuvenation by skin microbiome exchange
        for 3 treatments
  • Vaginal rejuvenation by vaginal microbiome exchange
       for 3 treatments
  • Oral chelation (detox) therapy per week
  • Consultation with PD Dr. Rainer Arendt
      o internal medicine, cardiology
      o personal coaching, autohypnosis, EMDR, HT (per hour) 
  • Consultation with co-therapists
      o Personal coaching / training (per hour)
      o Mogalates posture and embodiment therapy (per hour) 
  • Optional: Consultation with specialists in all medical fields
  • Holistic and biological addiction treatment (per week)
  • Holistic and biological treatment of eating disorders (per week)

 

 

REGAINING  YOUTHFULNESS  IN  THE  LITERATURE

“Youth — nothing else worth having in the world…and I had youth, the transitory, the fugitive, now, completely and abundantly. Yet what was I going to do with it?
I wanted freedom, freedom to indulge in whatever caprice struck my fancy, freedom to search in the farthermost corners of the earth for the beautiful, the joyous and the romantic.”

Richard Halliburton, 
The Royal Road to Romance (1925)

 

 

 

 

 

 

 

 

 

 

 

 

 

For your individually tailored health and regeneration package contact us

 

 

 

Saturday
Jul182015

"No More Dying. The Conquest Of Aging And The Extension Of Human Life" (Joel Kurtzman & Philip Gordon)

Fixing the ‘Problem’ of Aging: A Practical Scientific Approach to Life Extension in Good Health And Vitality

 

The Dolder Grand Health
Long Life & Vitality

PD Dr. Rainer Arendt
Internal Medicine & Cardiology FMH
Prevention & Regenerative Medicine


We offer gut microbiome exchange (transplantation) as novel opportunity for lifespan extension, prevention and treatment of various and so far difficult to treat ailments (auto-immune diseases, multiple sclerosis, vision loss due to uveitis, metabolic disorders, neuro-psychiatric diseases, Parkinson and addictions, cardiovascular disease, endocrine disorders and infertility, cancer).

 

It is the rich array of microbiota in our intestines that makes us the human beings we are, preserves our health, and determines our lifespan.

 

"Just as a vintage car can be kept in good condition indefinitely with periodic preventative maintenance, so there is no reason why, in principle, the same can’t be true of the human body."

 

As it appears, we have come closer to “solve aging” and get people to live, healthily, up to the apparent maximum of the human lifespan of about 120 years (the longest known/confirmed lifespan was 122 years) or even longer. Already today, we are able to restore vitality and extend lifespan by restoring the epigenetic control of our genome (it is epigenetics, the environment we carry with us in our gut that determines aging, not genetics, we do not need to change genes, we just change the gut bacteria that control our genes), by replenishing / restoring the youthful richness of our gut microbiome.

Our microbiomes contain well over 1 million genes, compared with our 23,000 genes. Furthermore, the commensal microbiome accounts for 90% of the cells in our bodies. Among other functions, these gastrointestinal symbiotes help form and maintain our immune system and aid in digestion, so their health is critical to our health. The understanding of how microbiota contribute to our mental and medical well-being is rapidly advancing.

 

A modern version of the age old dream of tapping the fountain of youth – is emblematic of the current enthusiasm sweeping the research community, to reverse engineer the biology that controls lifespan and “devise interventions that enable people to lead longer and healthier lives“.

Aubrey de Grey is enjoying the new buzz about defeating ageing. For more than a decade, he has been on a crusade to inspire the world to embark on a scientific quest to eliminate aging and extend healthy lifespan (he is on the Palo Alto Longevity Prize board). It is a difficult job because he considers the world to be in a “pro-aging trance”, happy to accept that aging is unavoidable, when the reality is that it’s simply a “medical problem” that science can solve.

His claims about the possibilities, and some unconventional and unproven ideas about the science behind aging, have long made de Grey unpopular with mainstream academics studying aging. But the appearance of Calico and others suggests the world might be coming around to his side, he says. “There is an increasing number of people realising that the concept of anti-aging medicine that actually works is going to be the biggest industry that ever existed by some huge margin and that it just might be foreseeable.”

De Grey isn’t the only one who sees a new flowering of anti-aging research (mostly been aimed at extending “healthspan”, the years in which you are free of frailty or disease, rather than lifespan, although an obvious effect is that it would also be extended, healthy people after all live longer). “Radical life extension isn’t consigned to the realm of cranks and science fiction writers any more,” says David Masci, a researcher at the Pew Research Centre, who recently wrote a report on the topic looking at the scientific and ethical dimensions of radical life extension. “Serious people are doing research in this area and serious thinkers are thinking about this.”

Life expectancy has risen in developed countries from about 47 in 1900 to about 80 today, largely due to advances in curing childhood diseases. But those longer lives come with their share of misery. Age-related chronic diseases such as heart disease, cancer, stroke and Alzheimer’s are more prevalent than ever.

“If a consequence of increasing health is that life is extended, that’s a good thing, but the most important part is keeping people healthy as long as possible,” says Kevin Lee, a director of the Ellison Medical Foundation, founded in 1997 by tech billionaire Larry Ellison, and which has been the field’s largest private funder, spending $45m annually. (The Paul F Glenn Foundation for Medical Research is another.) Whereas much biomedical research concentrates on trying to cure individual diseases, say cancer, scientists in this small field hunt something larger. They investigate the details of the aging process with a view to finding ways to prevent it at its root, thereby fending off the whole slew of diseases that come along with aging.

 

The standard medical approach – curing one disease at a time – only makes that worse, says Jay Olshansky, a sociologist at the University of Chicago School of Public Health who runs a project called the Longevity Dividend Initiative, which makes the case for funding aging research to increase healthspan on health and economic grounds. “I would like to see a cure for heart disease or cancer,” he says. “But it would lead to a dramatic escalation in the prevalence of Alzheimer’s disease.”

 

By tackling aging at the root that could be dealt with as one, reducing frailty and disability by lowering all age-related disease risks simultaneously, says Olshansky. Evidence is now building that this bolder, age-delaying approach could work. “We have really turned a corner,” says Brian Kennedy, director of the Buck Institute for Research on Aging, adding that five years ago the scientific consensus was that aging research was interesting but unlikely to lead to anything practical. “We’re now at the point where it’s easy to extend the lifespan…,” says David Sinclair, a researcher based at Harvard.

 

One of the novel approaches being tested is using gut microbiota from the young to reinvigorate the old, to help them live longer.

This appears to work by simulating the internal chemical properties of a young body. In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young.  Dawkins attributes inspiration for this idea to Peter Medawar. The basic idea is that our bodies are composed of genes that activate throughout our lifetimes, some when we are young and others when we are older. Presumably, these genes are activated by environmental factors (inside our gut), and the changes caused by these genes activating can be lethal. It is a statistical certainty that we possess more lethal genes that activate in later life than in early life. Therefore, to extend life, we should be able to prevent these genes from switching on, and we should be able to do so by identifying changes in the internal chemical environment of a body that take place during aging... .

The aim is to begin clinical studies of aging but these are difficult because of the length of our lives, though there are ways around this such as testing the length of telomeres in blood cells, the telomeres of young cells are longer than the telomeres of middle-aged cells, which, in turn are longer than the telomeres of old cells, and looking for signs of improvements in other conditions at the same time. Actually, the gut microbiome exchange appears to delay aging in every part of your body. As to when you might begin treatment, we suggest you could start treatment sometime between the age of 35 and 70 “because it keeps you healthy at least 10 years longer”.

 

 

 

“A lot of people spend their lasts decade of their lives in pain and misery combating disease,” says Craig Venter, San Diego based pioneering biologist and billionaire entrepreneur, …“I think it is possible to begin to do more about that than we are doing.” “I am not sure our brains and our psychologies are ready for immortality,” he says. “[But] if I can count on living to 100 without major debilitating diseases I would accept that Faustian bargain right now.”

“We’re tackling aging, one of life’s greatest mysteries,” we have a desire to make each day of our lives count, to make the most of life, to live longer and healthier.

 

 

 

PD Dr. med. Rainer Arendt
FMH Cardiology, Internal Medicine
Regenerative Medicine 

SWISS  PREVENTION  CLINIC
Klausstrasse 10
CH-8008 ZURICH
T +41 43 336 7260
M +41 78 825 0803
F +41 43 336 7261

rainer.arendt@swisspreventionclinic.ch

www.swisspreventionclinic.ch
www.patientcircle.org