10 replies to this topic

[reason]

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.

Link: http://dev.biologist...141/8/1627.full

View the full article at FightAging

[PWAIN]

This is very exciting stuff. If it can be developed further then we are on the brink of a revolution.

[Logic]

The FOXN1 protein is available though expensive:
http://www.abnova.co...d=H00008456-P01

It may have the potential to regenerate hair and skin as well as the Thymus?
http://ghr.nlm.nih.gov/gene/FOXN1
http://www.plosgenet...al.pgen.1002348

More PubMed searching is required.

Perhaps a rat study with this protein is in order?

[niner]

The mice in the study were genetically modified to make FOXN1 on command. If you start injecting transcription factors willy-nilly, the results may not be what you want. That PLoS Genetics link is broken. I couldn't figure it out.

[Avatar of Horus]

It doesn't work for me either, a search for the link gives this:

Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence

http://www.ncbi.nlm....pubmed/22072979

 

[Logic]

The mice in the study were genetically modified to make FOXN1 on command. If you start injecting transcription factors willy-nilly, the results may not be what you want. That PLoS Genetics link is broken. I couldn't figure it out.

I am aware of the above Niner, but I am talking about the protein produced by the FOXN1 gene.
ie: In stead of messing with gene expression to make more of the protein, just inject the protein. It looks like the kind of thing you would only want for a short time anyway as Foxn1 is switched off shortly after birth once the thymus, skin, hair follicles are fully formed.
Hence not the type of thing I would try on myself before trying it in rats 1st?

For the bald guys a liposomal formulation applied topically may be the answer to their prayers?

Soz for the broken link. ???

Edited by Logic, 01 September 2014 - 12:34 PM.

[niner]

The mice in the study were genetically modified to make FOXN1 on command. If you start injecting transcription factors willy-nilly, the results may not be what you want. That PLoS Genetics link is broken. I couldn't figure it out.

I am aware of the above Niner, but I am talking about the protein produced by the FOXN1 gene.
ie: In stead of messing with gene expression to make more of the protein, just inject the protein. It looks like the kind of thing you would only want for a short time anyway as Foxn1 is switched off shortly after birth once the thymus, skin, hair follicles are fully formed.

Yeah, that's what I mean- injecting the protein (a transcription factor) strikes me as hazardous on the one hand, and facing some delivery hurdles on the other. The mice were making it right inside the cell, while we would have to deliver it to whatever was the target cell. Probably not impossible, but not easy.

[John Schloendorn]

British scientists have for the first time used regenerative medicine to fully restore an organ in a living animal

 

 

Don't humans count as living animals?  http://www.ncbi.nlm....pubmed/18292808

 

Also, why do we think that reversing something that happens asymptomatically "soon after [...] childhood" would be helpful against "frailty in the aged".  40 years stand between thymic involution and the aging-related spike in infection.  How does this not suggest that they have nothing to do with each other?  (serious question --  I'm not trying to pick a fight.  I just really want to understand what anyone who believes this might be thinking).

 

 

 

 

Edited by John Schloendorn, 03 September 2014 - 05:17 AM.

[Logic]

 

 

The mice in the study were genetically modified to make FOXN1 on command. If you start injecting transcription factors willy-nilly, the results may not be what you want. That PLoS Genetics link is broken. I couldn't figure it out.

I am aware of the above Niner, but I am talking about the protein produced by the FOXN1 gene.
ie: In stead of messing with gene expression to make more of the protein, just inject the protein. It looks like the kind of thing you would only want for a short time anyway as Foxn1 is switched off shortly after birth once the thymus, skin, hair follicles are fully formed.

 

Yeah, that's what I mean- injecting the protein (a transcription factor) strikes me as hazardous on the one hand, and facing some delivery hurdles on the other. The mice were making it right inside the cell, while we would have to deliver it to whatever was the target cell. Probably not impossible, but not easy.

 

 

Ah; ok, so unlike GDF11 which can be injected as its a protein in the blood, FOXN1 is a protein n the cells.  Injecting it does not get it into the cells.

It may or ay not get into the cell by some means, but if it doesn't it would probably cause all sorts of unforeseen effects?

Edited by Logic, 03 September 2014 - 10:59 AM.

[Avatar of Horus]

... 
Also, why do we think that reversing something that happens asymptomatically "soon after [...] childhood" would be helpful against "frailty in the aged".  40 years stand between thymic involution and the aging-related spike in infection.  How does this not suggest that they have nothing to do with each other?  (serious question --  I'm not trying to pick a fight.  I just really want to understand what anyone who believes this might be thinking).

 
IMHO it's more of a gradual process which intensifies after puberty and slows down later a bit, but leads to the complete loss of thymus function in the eldery with aging, around 105-120 years of age.
 

The mice in the study were genetically modified to make FOXN1 on command. If you start injecting transcription factors willy-nilly, the results may not be what you want. That PLoS Genetics link is broken. I couldn't figure it out.

I am aware of the above Niner, but I am talking about the protein produced by the FOXN1 gene.
ie: In stead of messing with gene expression to make more of the protein, just inject the protein. It looks like the kind of thing you would only want for a short time anyway as Foxn1 is switched off shortly after birth once the thymus, skin, hair follicles are fully formed.

Yeah, that's what I mean- injecting the protein (a transcription factor) strikes me as hazardous on the one hand, and facing some delivery hurdles on the other. The mice were making it right inside the cell, while we would have to deliver it to whatever was the target cell. Probably not impossible, but not easy.

 
Ah; ok, so unlike GDF11 which can be injected as its a protein in the blood, FOXN1 is a protein n the cells.  Injecting it does not get it into the cells.
It may or ay not get into the cell by some means, but if it doesn't it would probably cause all sorts of unforeseen effects?

GDFs are signaling proteins, growth factors which generally signal from receptors in the cell surface to transcription factors in the nucleus, like the Forkhead box family, to regulate gene expression.

[Logic]

GDFs are signaling proteins, growth factors which generally signal from receptors in the cell surface to transcription factors in the nucleus, like the Forkhead box family, to regulate gene expression.

Ah; thx again Avatar.