Supplying Young Cells to an Involuted Thymus Produces Growth and Increased T Cell Production

Several distinct lines of ongoing (but unfortunately poorly funded) research aim to restore at least some degree of youthful activity to the thymus in old individuals, and researchers here demonstrate one of them: a process of introducing young thymus cells into an old thymus. The thymus plays a vital role in the generation of immune cells, and during childhood the rate of production is high. In early adulthood the thymus atrophies in a process known as involution, however, and the supply of new immune cells diminishes to a trickle. This is one of the important limiting constraints that determine the way in which the immune system ages. Restoring an old thymus should improve immune function in adults, and given that the degeneration of immune function in the old is a large component of the frailty of old age, this is an important and much underrated goal.

The thymus reaches its maximum size early in life and then begins to shrink, producing fewer T cells with increasing age. This thymic decline is thought to contribute to age-related T cell lymphopenias and hinder T cell recovery after bone marrow transplantation. Although several cellular and molecular processes have been implicated in age-related thymic involution, their relative contributions are not known.

Using heterochronic parabiosis, we observe that young circulating factors are not sufficient to drive regeneration of the aged thymus. In contrast, we find that resupplying young, engraftable thymic epithelial cells (TECs) to a middle-aged or defective thymus leads to thymic growth and increased T cell production. Intrathymic transplantation and in vitro colony-forming assays reveal that the engraftment and proliferative capacities of TECs diminish early in life, whereas the receptivity of the thymus to TEC engraftment remains relatively constant with age. These results support a model in which thymic growth and subsequent involution are driven by cell-intrinsic changes in the proliferative capacity of TECs, and further show that young TECs can engraft and directly drive the growth of involuted thymuses.



Superb news and I know of a human trial being done to see if it works in people. I hope it works for them as planned.

Posted by: Steve H at October 26th, 2015 11:09 AM

Steve, hopefully you commented Reason's article and not that fasting nonsense.

Posted by: Martin S. at October 26th, 2015 12:43 PM

@Martin yes I am talking about Reasons article. Fasting and Hormesis does not regrow the thymus. I know of an n = 10 human trial to regenerate the thymus being done now as part of a consensual study. I cannot elaborate further but no doubt we will find out more if it works.

Posted by: Steve H at October 26th, 2015 2:36 PM

@Steve H: but you're not, surely, suggesting that someone is doing a human trial of fetal (or even hESC-derived) thymic epithelial cell transplantation, yes? Did you perhaps read it too fast, and mistakenly take it to indicate that parabiosis regenerated the thymus, when they show precisely that it doesn't?

Posted by: Michael at October 26th, 2015 5:09 PM

Michael no sorry I didn't make myself clear. The thymus test someone is running is not to my knowledge stem cell related merely trying to achieve rejuvenation of the same organ. I will try to find out the details of intervention but I think it's pharmaceutical in nature.

Also the fact that parabiosis did not rejuvenate is no surprise. A lot of fuss is made about parabiosis and whilst it does contain beneficial factors I see stem cells as far more useful. It suggests that regenerative action can be obtained via replenisens fairly easily.

It also suggests that if one could work out why the engraftment and proliferation capability of TECs drops off so quickly you could mitigate the issue to allow extended proliferation and a longer functional life.

Whatever is dictating this rapid decline of proliferation is obviously not in the plasma otherwise young fresh cells would not engraft and regenerate the organ. So is it an in built process that the cell obeys shortly after differentiating from its precursor cell type? Or is it a paracrine effect from interaction with other cell types in the organ?

No idea I don't know much about the thymus but would genuinely be interested to know.

Posted by: Steve h at October 26th, 2015 6:04 PM

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