Blood, Sweat, and Years

Biomedical Sciences, Cardiovascular Health, Neuroscience

By Daniel Hass, PhD Candidate in Neuroscience

vampire

Vampires have been a part of popular culture for hundreds of years.

In 2009, the Atlantic published a short article entitled “The Meaning of Our Vampire Obsession”, outlining some of the potential psychological explanations for our societal obsession with these mythical bloodsuckers. Eight years later, this obsession shows no signs of abating, with various movies including ‘Hopekillers’, ‘The Vampyre’, ‘Love Bites’, and ‘Bursting Bubbles of Blood’ announced, or in some stage of production.

While I can’t speak to the psychological basis for the Vampire phenomenon, I’ve recently started to think that there might be a (very small) grain of truth to these stories and the age-old folklore that serves as its inspiration. This grain of truth is rooted in two facts about vampires. (A) They are immortal, and (B) They drink blood.

This is not to say that if you drink blood, you will live forever! However, the concept that transfusions from young blood can diminish the effects of aging has recently gained a lot of momentum in the scientific and biotech communities.

So how did this strange relationship begin between blood and age?

The first recorded successful human blood transfusion was introduced by James Blundell back in the mid-19th century. While his revolutionary technique was relatively obscure for several decades, it rapidly developed during WWI, by which time it was discovered that blood could be preserved for several days if refrigerated and treated with an anti-coagulant.

But it was Alexander Bogdanov, a Russian physician, philosopher, Bolshevik political figure, and science fiction writer who first supported the use of blood transfusion to preserve one’s youth. He believed that through this method, he could achieve immortality.  His theory that blood transfusions had a strong anti-aging effect drove him to undergo upwards of 10 transfusion procedures, and he wrote a book entitled “The Struggle for Viability: Collectivism Through Blood Exchange” to describe the stimulatory and rejuvenating effects of these procedures. Unfortunately and somewhat ironically, he died after being transfused with blood infected by malaria and tuberculosis.

elixer of life

The ultimate goal of Alexander Bogdanov. After several blood transfusions, he is said to have looked 10 years younger. But it is important to note that the speaker was a fellow transfusion enthusiast.

However for decades following his death, there were no detailed scientific inquiries to determine whether Bogdanov’s theories held any truth. Such inquiries began over 20 years later, in the form of parabiosis experiments. Parabiosis is the joining of two animals’ circulatory systems. It can be used to see how the various cells, proteins, and small molecules in the blood of one animal can affect the physiology of another.

Early parabiosis experiments in the 1950’s showed that combining a healthy rat’s circulatory system with one suffering from liver damage or irradiation resulted in improvement or recovery in the unhealthy animals. This established a grounding for further experiments, which could investigate other potential therapeutic applications of blood [1].

In the mid 1960s and 70s, parabiosis experiments made their way into gerontology (the study of aging). At that point, people began to implement heterochronic parabiosis experiments, in which the circulation of an older animal was connected to that of a younger one. These kinds of experiments showed that the circulation of older rodents detrimentally alters the physiology of younger rodents, and the circulation of younger rodents can improve on a variety of physiological features in older ones. The physiological features that are altered by younger or aged circulation include but are not limited to: immunity [2], stem cell regenerative capacity [3], metabolic function [4, 5], and even survival following radiation exposure [6].

parabiosis

A schematic of parabiosis. Both heterochronic (animals of different ages), and isochronic (animals of the same age). In these experiments, the circulatory system of two different animals are surgically attached to one another [1]. Image adapted from Smith et. al. 2015.

From these data, investigators found that changes in physiology that mark aging are controlled by specific factors in the blood. While specific factors such as Tissue Inhibitor of Metalloproteinases 2 (TIMP2) and Growth Differentiation Factor 11 (GDF11) and their unique effects on physiology are only now coming to light [7, 8], the very existence of circulating pro- or anti-aging factors implies that by changing the composition of a person’s blood, we may gain a degree of control over how that person ages [9].

So have I convinced you that there may be some truth behind the Vampire myth? Have I converted you to Bodonov-ianism? If not, I can understand your skepticism. So far, many of the individual studies I’ve mentioned look at the effect of blood composition on various physiological functions directly associated with blood—stem cells, the immune system, and metabolism are all positioned within or directly altered by the vascular system. What about other organ systems? The brain, for example, filters blood through something called the blood-brain barrier. Given that many disorders of the central nervous system (such as Alzheimer’s, Parkinson’s, and ALS) are age-related, how does young blood affect the aging brain? The past few years have seen a rapid evolution in this field, with data demonstrating that young blood can actually reduce age-associated cognitive deficits!

In 2014, a group led by Tony Wyss-Coray made headlines with its finding that transfusions of young blood into older rodents actually reverses age-related cognitive dysfunction [10]. The group even found a potential mechanism through which young blood stimulated the brain. According to their study, the reversal in cognitive dysfunction was mediated in part by circulating pCREB, which increases the ability of brain cells to form new connections (i.e. synaptic plasticity) and is decreased in aged blood plasma. When these older mice with cognitive deficits were given an inhibitor of pCREB along with a transfusion of young blood, there was no reversal of cognitive dysfunction.

Wyss-Coray and his fellow scientists are now working to find out which other circulating factors, if any, are lost or gained with age and the manipulation of which can restore brain function [11]. He’s additionally formed a start-up, Alkahest, which as of one week ago had just completed clinical trials investigating the potential for young blood plasma to reduce memory loss and cognitive dysfunction in Alzheimer’s disease. I expect that the results will be posted soon.

However, Alkahest is not the only company investigating the rejuvenating effects of young blood. Another start-up, named Abrosia and founded by Princeton grad, Jesse Karmazin, is also focused on using this scientific literature to inform therapies. Furthermore, there are also clinical trials testing out the transfusion of young blood, which in this case are patient-funded. So if you are over 35 years old and have $8,000 to spare, you can purchase a vial of young blood and undergo this promising, if somewhat ghoulish (and possibly vampirish), anti-aging therapy.

References:

  1. WENNEKER, A.S. and N. SUSSMAN, Regeneration of liver tissue following partial hepatectomy in parabiotic rats. Proc Soc Exp Biol Med, 1951. 76(4): p. 683-6.
  2. Butenko, G.M. and I.B. Gubrii, Inhibition of the immune responses of young adult CBA mice due to parabiosis with their old partners. Exp Gerontol, 1980. 15(6): p. 605-10.
  3. Conboy, I.M., et al., Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 2005. 433(7027): p. 760-4.
  4. Hrůza, Z., Increase of cholesterol turnover of old rats connected by parabiosis with young rats. Exp Gerontol, 1971. 6(1): p. 103-7.
  5. Tauchi, H. and K. Hasegawa, Change of the hepatic cells in parabiosis between old and young rats. Mech Ageing Dev, 1977. 6(5): p. 333-9.
  6. Warren, S., R.N. Chute, and M.W. Porter, The effect of parabiosis on life-span of rats stressed by radiation. J Gerontol, 1975. 30(1): p. 15-21.
  7. Loffredo, F.S., et al., Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell, 2013. 153(4): p. 828-39.
  8. Castellano, J.M., et al., Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature, 2017. 544(7651): p. 488-492.
  9. Rebo, J., et al., A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat Commun, 2016. 7: p. 13363.
  10. Villeda, S.A., et al., Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med, 2014. 20(6): p. 659-63.
  11. Wyss-Coray, T., Ageing, neurodegeneration and brain rejuvenation. Nature, 2016. 539(7628): p. 180-186.

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