Heterochronic Parabiosis, a Path into Exosomes

December 27, 2021

Heterochronic Parabiosis - It's Longevity Right in Your Blood

If I were to tell you that I could take an old mouse and make it suddenly perform like a much younger mouse by exchanging half its blood with a young mouse, you would raise an eyebrow. And if I showed you the data that you could prove increased muscle repair, better hippocampal stem cells, and reduced fatty liver (all the standardized examples of more youthful tissue) you would probably sit up and pay attention. Welcome to the concept of "heterochronic parabiosis". Yup. Take out the old blood and put in the new, and those mice look younger by any measure you can come up with.

The experiments have actually been a bit more complicated than that. Open up cloned old and young mice and stitch together two veins so they are constantly interchanging their blood. Then, observe how the older mice becomes younger, and the younger, older. Heterochronic parabiosis. Blood swapping.

That means there is something in the blood that is making them older. What is it?

The first insight came from a research project at Harvard by Kenyon back in the 90 where she found just one gene in roundworms, that when altered, doubled their lifespan. That was cool. The idea was hatched that aging is programmed into our genes.

Now, the experiments have now gone further. Conboy has shown that in cell culture you can identify two systems that can replicate the same process: TGF-beta which activates ALK5/pSmad and goes up with age, and oxytocin which activates MAPK and diminishes with age. From the same lab at Stanford, Villeda showed that brain learning gets better too. That caused lots of excitement and motivated multiple other labs to confirm those findings. The race was on. What was it?

Next step: take out half the blood from an old mouse and replace it with saline and 5% albumin. Same effect. No transfusion reactions between competing immune systems. Its something smaller than visible red cells.

What is smaller that carries all that effect. Exosomes. Let's introduce exosomes and basic cell biology. Exosomes are one of the hottest topics on the longevity market right now. What are exosomes? Every cell in your body, when exposed to some environmental stimulus responds by activating some new DNA. That makes messenger RNA. Many copies. All cells are connected to the tissue around them, and that mRNA gets transported across the pores connecting the cells. And some of it is exported into the blood in tiny, tiny vesicles called exosomes. Exosomes are about the size of LDL particles. Tiny. And there are millions of them in every milliliter of your blood. Wikipedia has a nice intro article that is quite up to date. Your blood is filled with mRNA, instructing you as a whole being, to respond to that stimuli in a structured, coordinated fashion through exosomes. That's what is hidden in your blood that is coded to make you older, or younger. You can react to malaria, sepsis, trauma by messaging all over with those exosomes. And they can make you "younger" or "older".

The implications for aging and longevity is interesting and significant. Our biology is destined for senescence. We pass on our genes and then fall apart in a structured fashion. We are programmed to get out of the way so that the next generation can have a go at it. The exosomes in our blood are passing out "nasty" signals. "Get white hair". "Get arthritis". "Lose muscle". "Lose brain." We are beginning to be able to read that code in our exosomes, the code of our DNA being spread out over all our bodies and exemplified in that circulating mRNA. The crude stitching together of two mice has opened quite a door. If we get it right, we can understand how to actually reverse that structured falling apart.......

www.What will Work for me. This exosome idea is probably going to be the next frontier in anti-senescent work. It is my belief that heterochronic parabiosis is a crude way with relevant results of revealing the power of exosomes. We can repair your membranes and make a safer environment for your cells by managing your plasmalogens. That story is still playing out. Now, how do we manage your exosomes? Stay tuned. I'm very interested.

References: Aging - Conboy, Harvard Review, Aging - Medhipour and Conboy, Conboy and Medhipour in Aging, Nature Medicine, Wikipedia

Pop Quiz

1. What is heterochronic parabiosis?                           Answer: Fancy name for sharing blood between two animals that have been stitched together like Siamese twins - of different ages but with identical genetic make up.

2. What role does in play in the history of medicine?                            Answer: It has carried the torch of that idea that aging is not inevitable, but rather programmed into our biology.

3. What are the implications of this programming?                      Answer: If it's programmed in, we can program it out.

4. What are exosomes?                              Answer: Ah, that is what has been causing the effect of heterotropic parabiosis. Tiny, LDL-sized, vesicles carrying messenger RNA to instruct your body to behave in various fashions.

5. Can I make myself younger by getting exosome infusions?                         Answer: I'm going to find out.....and if it's feasible, we will be doing it. This is way too interesting.

This column was written by Dr. John E Whitcomb, MD, Brookfield Longevity, Brookfield, WI.