Can Young Blood Reverse Aging?

youngblood no 1The notion that “young blood” contains substances that might rejuvenate older adults has been around for centuries. Current research indicates that there may be something to this idea after all.

A series of experiments by Thomas A. Rando, a professor of neurology at Stanford University School of Medicine, has shown that exposure to young blood can rejuvenate tissues in old mice.

Now the findings are being tested on humans.

Parabiosis Revisited

Blood remains a mysterious fluid; it carries hundreds of proteins and other substances. Although many of these proteins have been identified and their properties are well understood, there are still many others whose function is ambiguous. Among them are factors that could influence the aging process.

If scientists can understand how these proteins work, it might be possible to modulate the aging process, slowing it down or perhaps even reversing it.

In the 1950s, Clive M. McCay of Cornell University and his colleagues were the first to apply parabiosis–a 150-year old surgical technique– to the study of aging.

Parabiosis involves connecting two animals together surgically. The procedure hasn’t changed much since the earliest recorded experiment in 1864. It’s been done on small freshwater invertebrates, frogs and insects, but it works best on rodents.

McCay’s group used the technique to test a rejuvenation theory by grafting the circulatory system of a young rat to that of an old one.

The method, which mimics the natural occurrence of conjoined twins, allows scientists an extraordinary opportunity to test how circulating factors in the blood of one animal behave when they enter another.

The process was fairly simple: the investigators surgically joined the two rats by stitching the skin on their flanks together. Once connected, blood vessels grew, and blood flowed from the young rat to the old and vice versa.

When McCay did necropsies on these conjoined rodents, he found the cartilage of the old ratsMcCayClive appeared youthful, as if it had been rejuvenated by the exposure to young blood.

Science at the time was unable to provide answers as to why the transformation occurred. Only later did researchers begin to understood that stem cells are essential for maintaining the vitality of tissue like collagen, and that as people age, stem cells gradually decrease in functionality.

Stem cells need circulating factors in order to exert their rejuvenating effect—a key fact that could not have been verified in McCay’s day.  

“There were plenty of stem cells there,” recalls Dr. Rando, commenting on the aging rats in McCay’s pioneering studies. “They just don’t get the right signals.”

Between 1950 and 1980, parabiosis research led to significant medical breakthroughs in areas other than aging, such as endocrinology, tumor biology and immunology. After the 1970s, the technique fell out of favor, for no clear reasons.

Stem Cell Stimulation

In the early 2000s, Dr. Rando and his colleagues at Stanford, grew curious as to what signals old stem cells receive when bathed in young blood. They decided to revive Dr. McCay’s experiments.

He and his colleagues used the old parabiosis method—albeit with greater attention to reducing animal discomfort and mortality than in McCay’s time–to conjoin old and young mice for five weeks.

ParabiosisThey found that the muscles of the old mice healed about as quickly as those of the young mice, In addition, the old mice were able to grow new liver cells at a youthful rate, the Stanford group reported in 2004 (Conboy IM, et al. Nature. 2004: 433: 760-764).

They also observed that the young mice had grown prematurely old. Their muscles healed more slowly, and their stem cells turned into new cells at a slower rate than they had before exchanging blood with the elderly mice.

When an old mouse is united with a young one, and the conjoined pair share circulation, tissues of the old mice, including the heart, brain, and muscles, seem to be reborn by the young blood. Their fur even becomes shinier. Likewise, the blood of the old mice had substances that decreased the resilience of the young mice.

Rando’s experiments support the theory that there are compounds in the blood of the young mice that could stimulate old stem cells and revitalize aging tissue.

Since 2005, a handful of labs have been using parabiosis in a passionate pursuit of finding the substances responsible for the anti-aging phenomena. Researchers have begun to identify the components of young blood that are responsible for these changes.

The Big O: Oxytocin

In 2008, Irina and Michael Conboy, scientists at the University of California, Berkeley (formerly part of Rando’s Stanford team) identified one of the anti-aging factors circulating in the blood: Oxytocin.

This hormone is best known for its role in childbirth and bonding. The Conboys are quick to point out that oxytocin levels decline with age in both men and women.

When injected systemically into older mice, oxytocin quickly (within a couple of weeks) regenerates muscles by activating muscle stem cells. Oxytocin is already a drug approved by the US Food and Drug Administration for inducing labor in pregnant women.

But oxytocin is not the only circulating factor that could potentially reverse tissue senescence. Two other blood components have stood out in particular: a protein found in young blood known as GDF11, and a second factor known as B2M, which peaks in the blood of old mice, as it does in old humans.

Two high-profile papers published in Science in 2014, by a Harvard University team, reported that GDF11 levels decline in older animals, and that replacing it rebuilds muscles, the brain, and heart tissue.

But work described in May 2015 in Cell Metabolism, by a Novartis team, challenged GDF11’s rejuvenating powers. Their paper suggests that GDF11 actually inhibits muscle regeneration.

A paper published in July 2015, describes how B2M, when injected into young mice, impairs their memories.

Young Blood for Old Brains

In September 2014, a clinical trial in California became the first to start testing the benefits of ThomasRandoyoung blood in older people with Alzheimer’s disease.

The pioneering study launched by a private California-based company called Alkahest, which has as its mission statement, “developing therapies derived from blood and its components with a focus to improve vitality and function into old age.”

Thomas Rando is on the scientific advisory board for the company, which takes it’s name from a hypothetical universal solvent described by Paracelsus

The Alkahest trial, called the Plasma for Alzheimer Symptom Amelioration (PLASMA) study, involves a small cohort of 18 Alzheimer’s patients who are receiving infusions of either young human blood plasma or saline once weekly for four weeks, is expected to conclude by the end of this year.

The company plans to initiate further studies testing young plasma in the treatment of different types of dementia and age-related conditions.

Tony Wyss-Coray, a neurologist at Stanford University who founded Alkahest, says, “I think it is rejuvenation – we are restarting the aging clock”.

Some of his colleagues are a bit more guarded about making such claims.

Amy Wagers, a stem-cell researcher at Harvard University, who has identified a muscle-rejuvenating factor in young mouse blood, believes that the compounds in the blood are not transforming old tissues intoyoung ones, but are rather helping them to repair damage. “We’re restoring function to tissues. We’re not de-aging animals.”

There have been plenty of crushed hopes in the history of the anti-aging field. In the past 20 years, researchers have described the anti-aging properties of numerous treatments, including calorie-restricted diets; resveratrol, a chemical found in the skin of grapes; telomerase, an enzyme that protects the integrity of chromosomes; rapamycin, an immune-suppressing drug that extends lifespan in mice; and stem cells, which decline in function and number as people age.

Only two, caloric restriction and rapamycin, have been shown to consistently slow or reverse the effects of aging in mammalian tissues, but neither has been translated into a widely effective, easily implemented medical treatment. 

While the observations about young blood are certainly interesting, at this time there are no data—human or animal—showing that exposure to young blood or plasma will extend lifespan.

An experiment to test such claims would take time, maybe six years or more, and scientists would also need a lot of money to move forward with it.

“If we had funding to do this, I’d do it. But we don’t,” says Michael Conboy. Still, he adds, “I hope that someone, somewhere is.”

END

Jeannie Hallhas recently earned her Master’s degree in Nutrition and Integrative Health from Maryland University of Integrative Health (MUIH) in Laurel, MD. She is pursuing her CNS credential and is employed with Annapolis Acupuncture and Integrative Healing. Jeannie grew up on the Severn River, in Severna Park, MD and currently resides in Arnold, MD

 
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