Thymus Regeneration Demonstrated via Increased FOXN1

Researchers have demonstrated that they can produce a functionally youthful thymus in old mice by increasing levels of a single protein. There have been suggestions that such an approach might be made to work - tweak signal protein levels such that they are similar to those that existed during the early development of the thymus - but I have to admit that I wasn't expecting anything so impressive at this stage. It is an important advance if verified in other labs, as regeneration of the thymus is one of the methods by which the failing immune system in older people could be restored to greater function, at least partially ameliorating this one aspect of frailty in the aged.

One of the issues that contributes to the age-related decline of the immune system is a comparative lack of a supply of fresh immune cells, those capable of tackling new threats. The thymus, where these cells mature, has evolved to pump out a large supply of immune cells in childhood but it then atrophies soon afterwards - a process known as thymic involution. The adult thymus is a shadow of its former self and delivers only a trickle of new immune cells.

The SENS Research Foundation has been funding work on tissue engineering of the thymus, as a part of a portfolio of work on the foundations of human rejuvenation, and I'm sure that this will be a welcome addition to the list of potential strategies for thymic regeneration:

British scientists have for the first time used regenerative medicine to fully restore an organ in a living animal, a discovery they say may pave the way for similar techniques to be used in humans in future. The [team] rebuilt the thymus - an organ central to the immune system and found in front of the heart - of very old mice by reactivating a natural mechanism that gets shut down with age. The regenerated thymus was not only similar in structure and genetic detail to one in a young mouse, the scientists said, but was also able to function again, with the treated mice beginning to make more T-cells - a type of white blood cell key to fighting infections.

[The researchers] targeted a part of the process by which the thymus degenerates - a protein called FOXN1 that helps control how key genes in the thymus are switched on. They used genetically modified mice to enable them to increase levels of this protein using chemical signals. By doing so, they managed to instruct immature cells in the thymus - similar to stem cells - to rebuild the organ in the older mice.




This is probably the most interesting and important advance I've seen in a while. It opens up a lot of doors for other areas of the body as well.

Posted by: johnathan at April 8th, 2014 1:21 PM

Loads of layman questions and speculation spring to mind (as always):

1. If all it takes to maintain a healthy thymus is upregulation of one protein, why hasn't evolution done this? (Perhaps because not doing it doesn't cause problems until most humans 'in the wild' of prehistory would already have died by some other means).

2. Can this technique be done in humans tomorrow? I notice that they genetically engineered the mice (probably germline) so does this mean another delivery technique will have to be used in humans?

3. Which other labs are interested in verifying this? How long would that take?

Posted by: Jim at April 8th, 2014 3:01 PM

@Jim: the thymus is just a big fat special case of an organ with its early life withering away. Perhaps this is an evolved response to the threat of autoimmunity, but I have no insight into that. I think that the fact that it does wither makes this business of tricking it into thinking it is in a young body more of a practical outcome. I don't think you can't make hay in the same way by tricking a liver into thinking it is in a young body - it is just going to do the normal things that livers do at all ages. But in the special case of the thymus, the thymus in youth is subject to a very different set of evolved behaviors than in later life.

One of the things that makes this exciting is that it does seem to be simply a case of increasing levels of one protein in a specific location. That is much easier to translate into a treatment. I would expect this to be available via medical tourism a decade from now: it could probably be tested responsibly in a human subject by a competent lab with a few months of lead time right now if there were no such thing as medical regulation.

As to other labs and verification, this is a well known group, so I'm sure that this will follow on. You can't do something as loud and as easy to attempt as this and not have the rest of the research world and their lab mice lining up to replicate.

Posted by: Reason at April 8th, 2014 4:49 PM

Layman question:

Does anyone know how this could be translated to humans? I know it involves editing in a gene into the 'promoter' region of the FOXN1 gene that responds to the administered drug.

Could gene therapy using a vector and the CRISPR gene editing system be used to achieve this in humans? If not what are the roadbloacks? Would gene therapy not modify a high enough percentage of cells in the thymus?

Posted by: Jim at April 10th, 2014 2:18 PM

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