Amielle Moreno

For Halloween, Lab Land welcomes a guest post from Neuroscience graduate student Amielle Moreno, former editor of the Central Sulcus newsletter.

While recent studies have found evidence for the healing properties of blood from younger individuals, the fascination with “young blood” has been a part of the human condition for centuries.

In ancient Greece, Hippocrates introduced the concept that our health and temperament was controlled by the four humors, proposing that blood was the one responsible for courage, playfulness as well as hope. From the 16^th century story of Countess Elizabeth Báthory de Ecsed of Hungary, the idea of “blood baths” acquired decidedly more sinister connotations.

The “Blood Countess” holds the Guinness World Record as the most prolific female murderer. With 80 confirmed kills, Báthory might have lured up to 650 peasant girls to her castle with the promise of work as maidservants or courtly training. Instead of etiquette lessons, they were burned, beaten, frozen or starved for the Countess’ sadistic pleasure. Folk stories told how she would bathe in the blood of virgins to preserve her youth and beauty.

Portrait if Elizabeth Bathory, via Wikimedia

Humors remained a staple of traditional western medicine until the 1800s when medical research and our modern concept of medicine emerged. In this more enlightened age, people started sewing animals together to see what would happen.

In the mid-1800s, a French zoologist named Paul Bert first experimented with the creation of parabionts: the surgical joining of two animals, usually two rodents of the same species, in order to study the effect of one’s blood on the other. The first manuscript looking at parabionts was published by Bert in 1864, titled ‘Expériences et Considérations Sur la Greffe Animale’, which when loosely translated means ‘I’m a sick bastard and IACUC hasn’t been invented yet’.

As if parabiosis were a great rainy day activity for the kids, Bert described how to attach two animals together through their skin in an attempt to determine if a common circulatory system capable of exchanging nutrients would form: “the process is one the simplest: a strip of skin is removed along the opposite flanks of the two experimental animals; stitches and others handling systems that I described in my memoirs, maintain the animals attached and prevent frictions.”

In autopsy, he showed that vascular channels developed connecting the attached animals and that fluid injected in one would pass to the other. He was awarded the prize in Experimental Physiology by the French Academy of Science in 1866. Later, his discovery was memorialized in a Simpson’s Tree House of Horror’s episode featuring a “Pigeon Rat”.

Experiments with parabionts were not just grossly cool — they could be considered the beginning of transplant research. Fifty years after Bert, around the turn of the century, a scientist named Alex Carrel was performing experiments studying the ability to sustain living tissue outside the body, eventually connecting it to other living bodies. His methods of blood vessel connection won him the Nobel Prize. Once immunosuppressant drugs were developed, this research paved the way for organ transplants.

Transplanting organs is all well and good, but can it guarantee the promise of everlasting life? While not the goal of the study, the first evidence that healthy blood could extend lifespan came from a parabiont muscular dystrophy study in the 50s (Hall et al., 1959).

Recent parabiont research has been leading scientists to what Hungarian villagers have suspected: “dysfunctions associated with normal aging might likewise be rescued by parabiosis to a ‘healthy’, that is younger, partner and that lifespan itself might be amenable to prolongation by heterochronic parabiosis” (Conboy, 2013).

However, it isn’t a panacea. Guinn et al. found that there was no significant difference in post-surgery mortality between patients who received plasma from young versus old donors (Guinn, 2016). This study didn’t test the second best thing to being alive: being able to think.

Even though young blood won’t rejuvenate your skin, recent research discovered young blood “rejuvenating synaptic plasticity”. Neuroscientist Villeda and colleagues used heterochronic parabiont combinations of young and aged animals to determine changes in neuron growth and cognitive improvement. They found that “exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level.”

In the memory-associated brain area, the hippocampus, there was an increase in dendritic spine density and synaptic plasticity after pairing, a physiological marker associated with memory (Yang et al., 2009). Old animals paired with young ones also showed improvement in learning tasks like fear conditioning and spatial learning. While this means I’ll have to wait for advances in cosmetic surgery to reach Photoshop quality, having the cognitive capacity to remember to pluck that one mole hair on my cheek will have to do.

But what is so special about sweet, sweet virgin blood?

That question is yet to be completely answered, but there are some likely culprits. One difference between old and young blood could be immune function. The choroid plexus is the site where blood is filtered to make the cerebrospinal fluid bathing the brain. In the choroid plexus of older mice there were more signs of an inflammatory response than in younger mice (Baruch et al., 2014). When an immune signal called cytokine interferon-I was prevented, cognitive function improved.

There’s also a really boring anti-aging agent called “nuclear factor erythroid-derived 2-related factor” but his friends call him Nrf2. Nrf2 kicks in when cells are under oxidative stress and normally is involved with vascular smooth muscles. It’s also produced by neural stem/progenitor stem cells (NSPCs). These cells reside in the subventricular zone of your brain into adulthood and they depend on Nrf2 to maintain their function and survival. Upregulation of Nrf2 increased cognitive performance in elderly animals who have smaller NSPC populations (Corenblum et al, 2016). Other neuron pathways which are likely to be influenced by blood magic include the Wnt and TGF-B signaling pathways (Brack et al., 2007; Carlson et al., 2008).

Young blood is also associated with improved non-neuronal cell functioning. Heterochronic parabiont studies point to the role of growth differentiation factor 11 (GDF11) in improving the muscle structure and function in the older partner (Sinha, et al. 2014).

At Emory, Aloke Finn and colleagues identified a soluble factor called CD163, produced by macrophages, which increases during aging and limits muscle regeneration. Removing CD163 from blood may help restore the youthful ability to repair muscles after exercise or injury (Akahori et al, 2015).

From being one of the four humors to a source of rejuvenation, humans have always found “young blood” fascinating. With the other interventions that are known to promote synaptic plasticity being exercise and caloric restriction, Americans are clamoring for any alternative. The identification of factors with pro-aging or anti-aging effects could enable us to put these elusive properties in a jar and sell them.

Now, if you excuse me, I’m going to draw myself a Hungarian bath.