Parabiosis and young blood anti-aging in mice

 

 

Parabiosis and aging

When it comes to anti-aging science, creepy meets cool with “young blood” in new blood mixing studies just published.

The researchers report that blood from young animals literally makes older animals younger.

That striking claim is made by both of two independent teams. They published high-profile papers that just came out in Science and Nature Medicine. 

One of the teams, led by Lee Rubin and Amy Wagers of Harvard, has further narrowed in on one specific factor in blood. It is called growth differentiation factor 11 (GDF11), a focus of their Science report.

Science quoted Wagers as understandably very excited about this work:

“This is the first demonstration of a rejuvenation factor” that is naturally produced, declines with age, and reverses aging in multiple tissues

Tony Wyss-Coray of Stanford University in California led the other research team that focused on the rejuvenating effects of young blood on old brain tissue (also found by the Harvard team) as reported in their paper, Villeda, et al., in Nature Medicine.

Wyss-Coray is equally excited about the work as Wagers, but mentions how the research has made some folks a bit queasy:

“It’s still a bit creepy for many people. At meetings, people talk about vampires”

The new studies each involved an odd, but illuminating method whereby two mice are literally sewn together so that they share one vascular system and one collective pool of blood.

This process is called parabiosis and is more specifically termed heterochronic parabiosis when the mice involved are young and old (see Figure 1A from the Villeda paper above).

As an update, not much has come of GDF11 in the intervening years.

More on parabiosis

Parabiosis has been around a long time as a method. So has the observation that it could make older rodents have physiologically younger tissues sometimes. For instance, in a nice piece for the NY Times Carl Zimmer cites a 1950s study by Clive McCay of Cornell. In that work heterochronic parabiosis made the old rats have more youthful cartilage.

In the newer studies most of the effects of young blood on older mice were relatively moderate. While it’s not as though the old mice literally became dramatically younger, there were some very notable effects. One of the more consistent changes observed was about a boost in neurogenesis or the level of stem cell proliferation in certain regions of the brain to produce new, young neurons. It is also important to say that the younger mice seemed to get older in some ways too.

What is in the young blood?

It remains unclear just exactly what happens when old and young blood mix as well as what might make the older mice have some tissues appear younger. It could involve stem cells, but also likely involves many growth factors. Certainly GDF11 is not the whole story given the complexity of blood and GDF11 only had some of the powers of young blood, but GDF11 is still an intriguing factor.

I can almost imagine a future in a few decades in which a cocktail of say half a dozen defined factors could have real anti-aging effects. It’d be almost like “reprogramming” entire older human beings to be just a bit younger or perhaps at least not get physiologically older so fast…say an iPS cell-like effect on a grand, organismal scale. At this time it is hard to say how realistic such imaginings might be.

Another big question needs to be asked before we get too far in our imaginings: will this kind of effect will be observed in humans at all?

Mouse vs. human

Based on previous disappointing situations with mouse versus human experiments, it is reasonably possible that unfortunately it might may end up not working in humans, but I believe it is worth the effort to carefully study this kind of approach in humans. Indeed this kind of approach is already being proposed as the basis of an early clinical trial for human Alzheimer’s Disease patients. In such a scenario I suppose the intervention would be a repeated series of transfusions of blood from relatively young donors or GDF11. While this line of human clinical research seems in principle logical, again this kind of human clinical approach requires great caution, avoiding hype, and the careful advice of good bioethicists as well.

It is important as well to note that some very smart folks remain skeptical about this line of research and others indicate this is just the beginning of this research still so we need to be patient to see how this all plays out. For example, Science says:

Hope and hype are high in the antiaging research arena, and other researchers caution that the work is preliminary.

They quote neurosci guru Sally Temple that the papers are exciting, but “it’s a starting point”.

In other words, it’s exciting, but a lot more work needs to be done.

Clinics and bogus anti-aging

Sadly, we are also likely to see a dark echo of this legit work in the stem cell-related snake oil world. Probably even more dubious clinics will be selling infusions of young blood or “stem cells” from young blood making big claims about anti-aging powers…for example for aging baby boomers. We can’t stop these clinics entirely, but we in the stem cell field need to be activists and advocates in this area. We must collectively be constantly aware of them, be vigilant (for example some of them use images or videos of legit researchers to promote their research, which we need to quash) and do educational outreach to the public about the importance of evidence-based medicine. Too often these kind of outreach efforts by the stem cell field just do not happen.

Another challenge for a “young blood” kind of approach to anti-aging or to age-related diseases is that there could and likely would be side effects even in the context of responsible, careful, evidence-based kinds of anti-aging human clinical trials. Mobilizing old stem cells in old people or boosting angiogenesis in their tissues, for example, could in principle lead to higher rates of cancer or other unanticipated problems.

The bottom line is that I would say overall that this work is very exciting and has great potential in coming decades. However, great care is needed as the work eventually progresses into human clinical trials and we must educate the public about responsible research.