My dad is getting on in years. He’s 73 and is not exactly at the peak of health. In fact, I should count my lucky stars he’s still alive. He had several big health scares but the doctors have ‘worked their magic’ and he remains in good spirits, with an alert mind, and an ever-active daily schedule though with somewhat restricted mobility.
He asked me one day, me being the scientist of the family, what I thought of young blood transfusions. I stared at him in a mixture of horror and amusement. He had read online that young blood transfusions provided some health benefits and apparently asked his doctor for one! Of course the doctor politely declined, stating blood transfusions were typically reserved for emergencies and he could only have one if his haemoglobin levels dropped below a certain (very low) level. I asked if he would like my blood or my brother’s, but he said we were ‘too old’. Images of vampires and creepy old ladies who bathed in the blood of virgins to remain youthful flashed through my mind.. along with my dad drinking the blood of a teenager.
Perhaps the most well-cited studies of this wild idea, are those carried out by neuroscientist Dr Tony Wyss-Coray’s lab at Stanford University. He published two studies in Nature, one in 2014 and one in April this year, demonstrating cognitive improvement in old mice exposed to young blood.
The earlier study involved a surgical procedure called parabiosis that joined an old mice to a young mice such that they shared the same blood circulation. Five weeks after the surgery, the old mice showed significant cognitive enhancement. This was demonstrated by upregulation of genes associated with increased synaptic plasticity, an increased number of dendritic spines in the hippocampus (which is known to decline with age), and enhanced long term potentiation (LTP, an electrophysiological phenomena in the brain representing memory).
Importantly, they also injected old mice with the plasma from young mice over 4 weeks and found they exhibited improved memory in cognitive behavioral task. Essentially they measured the freezing time after auditory and electrostimulation – fear conditioning – and spatial memory – water maze. Pretty convincing results!
The second study done this year identified factors in the plasma responsible for this rejuvenating effect. Interestingly, they also found human umbilical cord plasma produced the same cognition-enhancing effects when injected in old mice, suggesting a common anti-aging molecule shared between mouse and man. The factor identified was tissue inhibitor of metalloproteinases 2 (TIMP2). Injection of this factor alone enhanced synaptic plasticity markers, LTP and improved cognition in various behavioral tasks. Conversely, inhibiting TIMP2 with antibodies reduced cognition and removing it from the young plasma prior to injection, also removed the cognitive-enhancing effects. A surprisingly clear-cut result in neurobiology.
A separate study by a group at Harvard University identified another factor in young blood, Growth Differentiation Factor 11 (GDF11), that induced “vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice.”
It’s no wonder that people are getting excited about this, and my dad may actually have a point!
Looking at the biotech scene, there are two biotechs involved in young blood therapy. One is called Alkahest, a Stanford spin-out with Dr Wyss-Coray as Chairman of the scientific advisory board. They have partnered with a Spanish pharmaceutical, Grifols, a world leader in plasma-based products. Grifols invested US$38 million in Alkahest with an additional US$13 million to develop and sell Alkehest’s plasma-based products (see Press release).
Another company is Ambrosia, started by Princeton graduate Jesse Karmazin, which has sparked some controversy by carrying out a human clinical trial with a US$8000 participation fee. Judging from the website that has very little detail at all, much less about science/technology, it seems to be purely a money-making endeavor that thrives off fear of aging. They are using healthy volunteers and do not even have a placebo group in the trial. Most in the field have written it off as “the scientific equivalent of fake news”, but undoubtedly, Ambrosia is not likely to suffer from a lack in participants desperately seeking the fountain of youth.
While we might be able to one day find the ‘cure for aging’, let’s not lose touch with reality. As physicist Sean Carroll says in “The Big Picture”:
“But eventually all of the stars will have exhausted their nuclear fuel, their cold remnants will fall into black holes, and those black holes will gradually evaporate into a thin gruel of elementary particles in a dark and empty universe. We won’t really live forever, no matter how clever biologists get to be”
*For a great review on the current state of anti-aging efforts in biotech/pharma, read this: João Pedrode Magalhães et al., “The Business of Anti-aging Science“, Trends in Biotechnology, 35(11), 2017
**After this post was published, results of Alkahest’s trial of 18 participants was released showing young blood transfusions while safe produced minimal, if any, benefits – reported in Science Magazine