In a landmark study sure to provoke interest, researchers from the University of Edinburgh have regenerated an aged organ in vivo, inside a living animal to its youthful state though noninvasive manipulation of genes. Its a breakthrough that not only brings hope for a wide variety of age-related ailments, but which fundamentally challenges our idea of what aging is. This study treats the natural impacts of of time like symptoms of a disease and by treating those symptoms it seems to have tracked the cells back to their pre-disease (youthful) state.

The organ in question is the thymus, a small immune node that sits near the heart. It produces T-cells, one of the bodys most important immune response units, but over the course of a lifetime the thymus shrinks and T-cell production slows. This is thought to be one big reason (one of many) that elderly people suffer decreased immune response relative to younger people. This study used1- and 2-year old mice, and saw the typical drop in both thymus size and T-cell production with age.

The thymus is one of the most important parts of the immune system, especially in younger people.

Prior research had already identified a protein called FOXN1 as likely linked to thymus degeneration; its expression levels in the thymus seem linked to that organs fate. The mice in this study were bred with a specific genetic sensitivity, however, so that when exposed to the drug tamoxifen they would begin producing fully youthful levels of FOXN1, regardless of their actual age. It should be pointed out that the fact that these were genetically engineered mice is more crucial to the experimental setup than the therapeutic one; without the need to control for variables, scientists could plausibly increase FOXN1 levels through less convoluted measures.

The results? Mutant mice treated with tamoxifen showed total or near-total regeneration of their youthful thymus, while control mice also given tamoxifen showed predictable thymus function for their age. This held true for both the size of the organ itself and the abundance of the T-cells it produces. The regeneration seems to arise from the fact that FOXN1 is a transcription factor that controls expression of several other genes, and that these genes activate stem cell-like action in some thymus cells. By restoring FOXN1 levels, the researchers seem to have convinced the thymus to de-age itself at least, in this one very specific way.[DOI:10.1242/dev.103614]

The researchers are quick to point out the possible benefits to elderly people, or those afflicted by immune diseases. Increasing the ability to fight infection could also revolutionize hospital medicine, helping vulnerable patients fight infection by overclocking the thymus to produce a boost of white blood cells. Restoring the immune response of sick and elderly people would be, without an ounce of hyperbole, one of the most important medical advances in all of human history.

A separate study found that improper FOXN1 function causes a wasting immune disease. Sad

But this study is a far cry from proof that such utility could actually exist. If nothing else, it stands as an uncomfortable challenge to our ideas about just what agingis. Has the thymus really been regenerated or is it simply bigger and more active than it used to be?We do have a few relatively non-arbitrary measures of cell age, in particular measurements of telomere decay. Telomeres are long stretches of inactive DNA that cap our chromosomes on either end, and which seem to fray and shorten as cells live and replicate. A functional regeneration such as this one, coupled with genetic implants to re-lengthen telomeres and undo other sources of aging damage, could be difficult to distinguish from literal reversal of the aging process. (Read:What is transhumanism, or, what does it mean to be human?)

Thats a long way out, however. In the extreme long term, patchwork replacement of organs and body parts is even prophesied to allow immortality, and this study shows that we might be able to supplement grown organs with regenerated ones. Theres no telling how many tissues might be usefully regenerated with such a simple molecular switch but theres also currently no telling if these regenerated thymuses will continue to function well, or if such manipulation could cause unintended side-effects.

A lot more research is needed before human applications could even be discussed, but its an enticing goal. Any tool that could maintain the bodys own immune system could end up saving both lives and healthcare costs immensely of course, as weve discussed previously though, there could be some massive problems if we all start living to 100 or more.

View post:

Gene therapy successfully regenerates an old organ inside a living animal