Immune System Rejuvenation Achieved Through Targeted Cell Destruction

Our innate and adaptive immune systems vigorously assault bacteria, viruses, fungi, and other trespassers that can cause us harm, but their efforts decline with age. A poorly functioning immune system is an important component of age-related frailty - a time in life when you can no longer shrug off even the common illnesses that bothered you little when you were young. Diseases that young people barely notice can kill the elderly, and the failing immune system can be blamed for much of this.

Progressive immune failure is unusual in that it is just as much an issue of configuration as it is of the accumulating biochemical and cellular damage that affects all bodily systems in aging. The body is limited in the number of immune cells it supports, and if the current crop of cells have become largely useless - because they are too busy chasing the memories of a lifetime of pathogens to adapt to new threats - then you have a largely useless immune system. Your body still has the theoretical capacity to mount a better immune defense, but not with the immune cells it has. Unfortunately, that unhelpful population of cells blocks the creation of new, fresh immune cells by virtue of the fact that it exists at all: it's using up the available space to no good end, but your body has not evolved to recognize the need to remove them.

I should add that this is a very high level and simplistic explanation; a little more can be found back in the Fight Aging! archives:

Our immune systems do a great job for most of our life spans, and even past our peak reproductive life spans - but that's all that evolutionary pressure will ensure. After that, you're on your own. The price of an evolved system that does amazingly well right out of the gate in a newborn is an evolved system that serves the old very poorly.

All is not gloom, however, and we can look ahead to very near-future biotechnologies that will address this issue and go some way towards restoring good immune function to the old. Scientists are in the midst of developing a new generation of technologies that can very precisely kill specific cell types - the cancer research community has been demonstrating targeted cell killing methods in the laboratory for some years now. These cell killing technologies are perfect for use in attempts to restore an age-damaged immune system to a more youthful state by culling the unwanted cells:

Now in theory, an old immune system that is top-heavy in memory T cells could be at least partially restored (remember that there are other issues and degenerations beyond the one I discuss here) by destroying all the unwanted memory cells. In recent years researchers have destroyed and then used stem cells to recreate the entire immune system in human trial patients, and have done this to essentially remove misconfigured immune cells that were the source of an autoimmune disorder. If that can be done, then it should certainly to be possible to take one of the new generation of targeted cell destruction technologies developed in the cancer researcher community and use to it destroy only a specific population of T cells.

I've been talking about this for a few years now, so I'm always pleased to see signs of progress in efforts to reverse declining immune response by selective destruction of immune cells. Here is an example of one early stage effort that demonstrates a benefit resulting from this approach: the researchers removed the existing population of immune cells, which caused the natural generation of a better-equipped replacement population of cells, and a consequently better immune system. That replacement process cannot happen without some intervention to remove the cells in the first place:

Aging is associated with a decline in [the creation of B-cells] in the bone marrow and accumulation of long-lived B-cells in the periphery. These changes decrease the body's ability to mount protective antibody responses. We show here that age-related changes in the B lineage are mediated by the accumulating long-lived B cells.

Thus, depletion of B-cells in old mice was followed by expansion of [populations of progenitor cells that create B-cells and] a revival of [lymphopoiesis, or the creation of B-cells] in the bone marrow, and generation of a rejuvenated peripheral compartment that enhanced the animal's immune responsiveness to antigenic stimulation.

Collectively, our results suggest that immunosenescence in the B-lineage is not irreversible, and that depletion of the long-lived B cells in old mice rejuvenates the B-lineage and enhances immune competence.

As a first step, this looks promising. We can look forward to seeing much more of this sort of approach tested and trialed in the next few years.

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