Tag Archives: rejuvenation

640px-Blundell27s_method_of_blood_transfusion_Wellcome_M0014653

Vampires might be on to something: blood from young humans rejuvenates old mice

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Credit: Wikimedia Commons

Plasma, the liquid part of blood, has been time and time again shown to have rejuvenating properties when transferred from young to old mice. A group of researchers from a company called Alkahest wanted to investigate whether the same effect held true if human blood was injected into the old mice. Indeed, the effects were much of the same as the young human blood led to improved memory, cognition, and stamina.

True blood

Previously, studies showed that plasma can rejuvenate the brain and other organs like the liver, heart, or muscle tissue. This seems to work only when the blood is transferred from the young to the old. If done in reverse, young mice begin to show signs of brain aging.

By now, the dark plot of some vampire movie might come to mind. But the implications of such research go far beyond myth and legend — we could be coming across a holy grail with great impact for the cosmetics and pharmaceutical industries. Our lifespans could be significantly augmented, some researchers believe. But the most meaningful benefits of vampire-like transfusions might be reaped by the chronically ill. People with cancer who resist muscle loss have better chances of survival, for instance.

Since the early 2000s, researchers have been making blood transfusions to study these effects. It seems like a protein called GDF11 found in blood plasma is responsible for the rejuvenating effects, as identified by Harvard researchers in 2012. In both mice and humans, GDF11 falls with age. We don’t know why this happens yet but there are hints that the decline occurs due to growth control mechanisms. We can only hope to learn more once the first human trials involving young-to-old blood transfusions begin.

Sakura Minami and colleagues at Alkahest made a first step in this direction by transfusing the blood taken from 18-year-old humans and injecting them into 12-month-old mice (equivalent to 50 years of age in human years). Prior to the experiment, these elderly mice showed clear signs of aging like poor memory and decreased physical activity.

For three weeks, the mice were injected with human plasma twice a week. At the end of the human plasma treatment, the mice were evaluated by a range of tests. Young, 3-month-old-mice, as well as a elderly mice who did not receive the plasma injection served as the controls and yardstick.

The team found human plasma, though injected in a foreign organism, does have the power to rejuvenate. The plasma-treated mice were far more physically active, running around an open space almost indistinguishably from young mice. Regarding cognition, the treated mice remembered their way around a maze much easier and better than untreated mice. When the brains of these mice were examined, Minami and colleagues found new neurons developed in the hippocampus, a growth process scientists call neurogenesis.

“Young human plasma improves cognition,” says Minami, who presented her findings at the Society for Neuroscience annual meeting in San Diego, California, on Monday. “Their memory was preserved.”

“It’s more or less what we would expect,” says Victoria Bolotina, at Boston University in Massachusetts. “The blood of young people must have something in it that’s important for keeping them young,” she told New Scientist.

At the meeting, Minami said her team had identified several factors from young blood that might be responsible for these effects. Some might cross into the brain while others might act remotely, but she did not share the exact mechanisms. The findings appeared in the journal Nature.

“There’s anecdotal evidence that people experience benefits after blood transfusions,” she says — evidence that might one day translate into anti-aging treatments but also urgent rejuvenation for the most vulnerably ill.

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Protein Dracula: transferring young mice blood to older mice reverses aging

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This Sunday a trio of landmark studies were published each discussing an aspect of a wider picture:  reversing aging in the muscles and brains of old mice simply by transfusing blood coming from younger mice. The effect is credited to a key protein found in much higher concentration in the blood of younger mice. So far, the findings are niched to a particular breed of mice, but if the results can be replicated with other strains as well, then trial on humans might not be far off.

Vampire biology

It all started when researchers at Harvard University  found that a protein called GDF11 could cause a mouse heart thickened with age to revert to a youthful state. Now, other groups have found that these effects extend that work to the mouse brain and muscle.

In one study, Amy Wagers, a professor of stem cell and regenerative biology at Harvard University, and colleagues joined the blood vessels of young and old mice together so that they might effectively share their blood – a procedure called parabiosis. They measured profound changes to muscle stem cells in the older mice that made the cells appear more youthful. Structural changes to the muscles were also recorded.

[ALSO READ] Old organ regenerated to youthful state in elderly mice using gene manipulation

Next, they injected the protein that had been shown to rejuvenate hearts into the older mice. The primary effect of GDF 11 appears to be increased blood flow, and it was noted that the older mice who had elevated concentrations of GDF 11 were able to repair muscle damaged after injury. Although some individual mice did not change much, on average, the treated mice could run nearly twice as long on a treadmill as older mice not given the protein. The protein had no effect when injected into younger mice, as reported in the journal Science.

Better muscles, better brain, better bodies

Then in a second study, Dr. Lee Rubin, director of translational medicine at the Harvard Stem Cell Institute, found that after parabiosis, the older mice had an increase in the branching network of blood vessels in the brain and in the rate of creation of new brain cells. It also bolstered function in the region of the brain involved with olfaction, which is how we interpret smells.

An important caveat about the research that needs to be mentioned, however, is that it was done on a particular strain of mouse that is inbred. The protein’s effect needs to be tested on more genetically diverse strains as well before any thought can be given about extending the work to human clinical trials.

In the third study published in the journal Nature Medicine, researchers from the University of California, San Francisco and Stanford used parabiosis to search for changes in gene activity in the brain that might help point to how young blood had its effects. Interesting enough, the researchers found key changes in the gene activity involved in the connectivity of brain cells in a region called the hippocampus – the part of the brain responsible for memory storage and retrieval.

When the Californian researchers transfused blood from young mice to older ones, the animals experienced an improvement in age-related memory tasks, like locating an underwater platform and remembering environments where they had a bad experience (nasty electrical shock).

While, all three studies – though they differ in their approach – seem to point in the direction that GDF 11 has key rejuvenating benefits, it’s still too early to make any guesses. More work needs to be made and until then, it’s a good idea not to try transfusing all of you blood with that of your niece.

mouse age reversal

Old organ regenerated to youthful state in elderly mice using gene manipulation

mouse age reversal

Photo: guardian

The popular myth of the fountain of youth tells the story of a magical spring that restores youth to anyone who drinks from it. Scientists working with longevity research have made important strides forward in recent years, however all of these efforts concentrate on prolonging life and slowing the effects old age has on the body, not reversing them. A breakthrough by researchers at University of Edinburgh may cause a paradigm shift in regenerative medicine after an old organ in elderly mice was regenerated into a youthful state, simply by manipulating a single gene.

The thymus is a specialized organ in the immune system. The functions of the thymus are the “schooling” of T-lymphocytes (T cells), which are critical cells of the adaptive immune system, and the production and secretion of thymosins, hormones which control T-lymphocyte activities and various other aspects of the immune system.

With old age, however, the thymus becomes progressively smaller making the body more vulnerable to infections and diseases. In fact, by the age of 70 the thymus is just a tenth of the size in adolescence. So, the team at the MRC Centre for Regenerative Medicine at the University of Edinburgh thought of a way to regenerate the thymus.

Rejuvenating elderly mice

Previous research showed that a gene, called Foxn1, naturally gets shut down as the thymus ages, so the Edinburgh researchers concentrated on boosting the gene back to youthful levels. A drug that targets this protein and instructs stem cell-like cells to rebuild the organ was made and given to elderly mice. The results were striking: just by manipulating this single gene, the thymus in elderly mice increased in size and made more T-cells. It almost completely regenerated.

“Our results suggest that targeting the same pathway in humans may improve thymus function and therefore boost immunity in elderly patients, or those with a suppressed immune system. However, before we test this in humans we need to carry out more work to make sure the process can be tightly controlled,” said Clare Blackburn, Professor of Tissue Stem Cell Biology, MRC Centre for Regenerative Medicine.

It’s not clear why the thymus shrinks with age, but one theory says it’s because more energy is diverted towards reproduction once entering adolescence. As such, if human trials are to begin, there needs to be a tightly controlled setting to ensure no negative side-effects are encountered. The discovery could also offer hope to patients with DiGeorge syndrome, a genetic condition that causes the thymus to not develop properly.

“One of the key goals in regenerative medicine is harnessing the body’s own repair mechanisms and manipulating these in a controlled way to treat disease. This interesting study suggests that organ regeneration in a mammal can be directed by manipulation of a single protein, which is likely to have broad implications for other areas of regenerative biology,” said Dr Rob Buckle, Head of Regenerative Medicine, Medical Research Council.

But what about other organs? The heart, lungs, liver, maybe there’s a way to regenerate these by gene manipulation as easily as it was for the thymus. The full paper can be read here.

Also worth noting is a different path that leads to the same destination – reactivating the enzyme telomerase, which repairs damaged tissue and reverses signs of aging, as shown by studies on mice at the Dana-Farber Cancer Institute, Harvard Medical School. A synergy between the two methods may propel medicine into a new age.