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Can Blood Transfusions Slow Aging?

Young blood in an older body. Will it work? This episode features audio from:

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Today, we answer what may sound like a very unusual question: Can revitalizing blood with blood transfusions slow aging?

In our first story, we consider gruesome experiments that surgically attach old animals to young ones to show that there is something in the blood that causes aging.

One of the major hallmarks of aging is the decline of regenerative capacity of our tissues. There are stem cells residing in our muscles, for example, that can leap into service at the first sign of injury to repair any damage. Is the waning of tissue-renewing abilities due to some intrinsic property of aging stem cells, or a consequence of being trapped in an aging body? To find out, researchers grafted the muscles of old rats into young rats, and vice versa. Inside the young rat, even the weak atrophied muscles of extremely old rats at the end of their lives regained their strength, volume, and ability to regenerate. They became young again; so, the capacity was still there all along. And young muscles in old rats lost renewal capacity. So, it appeared to be something about the surrounding milieu, rather than inherent defects with age.

To see if the critical elements were circulating in the bloodstream, old muscle stem cells were cultured in the blood of young animals. This alone had a rejuvenating effect, suggesting that there may be some sort of vitalizing factors in youth that we lose as we age (or inversely some repair-repressing component that builds up). Either way, this may be good news, because if we can find out what those factors are, we may be able to slow aging or even reverse it.

Could more than just muscle be restored? What about the brain and all the other organs? To see the extent in which circulating factors might play in affecting aging, researchers turned to a macabre procedure called parabiosis, from the Greek para, meaning “next to,” and bios, for “life.” It was an attempt to recreate the phenomenon of conjoined twins in a lab by sewing animals together to study the effects of transmissible factors.

Conjoined twins are often referred to as “Siamese twins,” due to the notoriety of a 19th century pair of Siamese-American brothers joined at the chest. The Blažek sisters are the only conjoined twins on record ever having given birth. Josepha and Rosa Blažek were quite literally joined at the hip. When Rosa got pregnant, both of their breasts developed and started lactating, supporting the theory we now know to be true today that lactation is regulated by hormones that circulate in the blood. So, what about aging factors circulating in the blood?

Surgically, researchers can connect the skin, circulation, muscle walls, body cavities, and shoulder blade joints of two animals. Early attempts to graft different species failed—for example, mammals to birds, or a cat to a rat. But in 1862, a pioneering French scientist was able to successfully pair together two young rats.

The first heterochronic union (hetero meaning “different,” khronos meaning “time”) was created in 1955 to answer the question: what would happen if you bathed the tissues of an old animal in the blood of a young one? The title of the paper was “Experimental Prolongation of the Life Span.” Old rats hooked up to young rats lived about 20 percent longer than old rats hooked up to one another. Subsequent experiments showed old mice coupled with young became healthier, stronger, and smarter. Aged tissues in a number of organs were rejuvenated, including the brain, heart, pancreas, skeleton, and muscles.

That doesn’t necessarily mean that aging was slowed, though. Rather than some sort of restorative bloodborne factor, maybe the older animals were just taking advantage of the reserve organ capacity in the younger animals––like having an extra set of youthful kidneys. To see whether there’s some aging or anti-aging transmissible element, rather than sharing organs and an entire circulatory system, what about just getting a transfusion of young blood? After all, as an American Aging Association journal review concluded: “The use of parabiosis in humans is currently not performed due to the surgical complications and resulting undesirable lifestyle.” Ya think? But getting a transfusion of young blood would be easy. Does it work? We’ll find out next.

Next up, get ready for the mind-blowing twist in the mystery of why the injection of blood from young animals into old ones has a rejuvenative effect.

“Vampires 2.0? The ethical quandaries of young blood infusion in the quest for eternal life.” In an episode of the TV series Silicon Valley entitled “The Blood Boy,” a tech guru hires a young assistant from whom to transfuse pints of blood in an attempt to slow down his aging. The restoration of youth by bathing in or drinking the blood of youth is a centuries-old trope dating back at least to the futile attempt of ailing Pope Innocent VIII, who in the 1490s failed to live up to his name by apparently drinking the blood of three ten-year-old boys who—though a bargain “costing only one ducat apiece’’—died in the process.

Might there be something to it, though? Though young blood did not have a significant impact on lifespan, otherwise infusing the blood of young animals into old did have rejuvenating effects on multiple organs, similar to full-blown parabiosis, as I talked about in the last video. In fact, not only does the infusion of young mouse blood improve age-related cognitive dysfunction in old mice, young human blood—taken from umbilical cords—worked too (in mice engineered to not reject the foreign tissue). This led to ongoing clinical trials offering weekly infusions of blood products from young donors to patients with mild to moderate Alzheimer’s disease. But there may be an easier way.

Yes, the injection of blood from young mice into old can improve memory and learning, suggesting there’s some kind of restorative youth factor. But the injection of blood from old mice into young can worsen memory and learning, suggesting that instead there’s some sort of debilitating aging factor. Or maybe the old blood is just diluting the revitalizing factor in the young mouse. Or, for that matter, maybe the young blood is diluting the debilitating factor in the old mouse. The fact that old blood appears to make things worse more than young blood makes them better suggests maybe the latter is the case. But you don’t know until you put it to the test.

Ready for a mind-blowing shift in perspective? Instead of infusing young blood into old mice, researchers at UC Berkeley just diluted the blood of old mice by siphoning off the plasma (the liquid portion of the blood), and essentially replacing half of it with water. If the regeneration seen in heterochronic parabiosis and blood transfusions was due to some fountain of youth factor in young blood, then nothing should happen, right? But if all the young blood was doing was diluting some debilitating aging factor, then the water should work just as well. And it did. The rejuvenation in the liver was similar to parabiosis or transfusion, and in the muscles and the brain, it was even better. So, most, if not all, the benefits could be replicated by simple dilution, including an improvement in cognitive capacity.

That’s good news, since there’s already an FDA-approved procedure in use today known as therapeutic plasma exchange. It’s usually used to filter out toxins or autoimmune antibodies, but why not try using it to try to dilute old blood to treat Alzheimer’s disease? And that’s exactly what researchers did.

Hundreds of Alzheimer’s patients were randomized to a therapeutic plasma exchange procedure or a placebo (sham) procedure. And though it didn’t seem to help those with mild Alzheimer’s disease, those with moderate Alzheimer’s randomized to the real procedure experienced about 60 percent less cognitive and functional decline over a period of 14 months. This is in stark contrast to mainstay treatments for Alzheimer’s, like the drug memantine, that can help with symptoms but don’t actually alter the course of the disease. And the added advantage over blood transfusions, as a Director of an Institute of Biomedical Ethics put it: “There is something peculiar about the old literally feeding on the young.”

 

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