Will Rejuvenation of the Thymus Require Rejuvenation of the Lymphatic System?

Some of the decline of the adaptive immune system is caused by the very slow replacement rate of T cells. A slow replacement rate makes the immune system look a lot like it is bounded in size, and within those bounds can be found an ever-increasing number of broken, misconfigured, and malfunctioning cells, their population growing faster than it can be replaced. T cells are created in the bone marrow but mature in the thymus, and the age-related atrophy of the thymus is a primary cause of this slowdown in cell replacement. Thus there is considerable interest in our community in finding ways to restore functional thymic tissue, capable of turning out new T cells at a faster pace. This article takes a look at one of the scientific groups involved in this research.

What if you could experience full health until the very end of your life? Researchers think long-lasting immunity from disease might be possible - if the thymus and the T-cells it produces to fight infection can be brought back to work efficiently. As we age, cells that defend against infection are gradually lost because we stop making them. This is particularly true with T-cells, and the result is often an onslaught of infectious diseases later in life. By rejuvenating the immune system, the researchers are hoping to stop that onslaught.

"T-cells are made in the specialized T-cell factory that sits behind our chest bone, and this is called the thymus. T-cells are critical in orchestrating an immune response. However, by the time we have gone through puberty, the thymus is churning out only one-tenth of the T-cells it made before puberty. What's more, there is evidence that between age 40 and 50, there's another tenfold drop. Down to 1 percent. So, the good news is it's not down to zero. The bad news is you're not producing many T-cells. That's really the earliest manifestation of our aging, the shrinking of the thymus."

However, even if the thymus remained plump and pumped out T-cells at a mad rate, it would be for naught. With age comes the sullying of the lymphatic system, whose job it is to circulate lymph and serve as a highway for T and other immune cells, equipped with vital communication checkpoints. Although T-cells still enter the lymph system in older people, the scant T-cells that are produced can't readily enter the lymph nodes. "Aged lymph nodes aren't able to effectively call in the cells from the outside, so fewer cells arrive. Moreover, when the cells arrive, they don't move inside like they should. Inside the lymph node is a superhighway meshwork, and we have found that this really gets messed up in aging."

So, researchers are formulating a novel plan of attack. "The idea here is that we want to rejuvenate both the thymus and the peripheral lymph organs, so both the factory that makes the cells and sites where the T-cells go to do the real work of defense against infection can once again work together. We feel like we will never get to rejuvenation if we work only on the thymus. If we are successful, we will see an improvement in immune defense and survival. Older adults are still by far the largest population for which infectious diseases still represent a significant risk. Our dream is to bring back the thymus and the T-cells to work the way that they should, particularly if we can fix the lymph nodes. That's not only going to benefit the T-cells but it will benefit the entire immune system. Our lifespan has been extended, but the problem is that for a sizable number of people, they're dealing with chronic diseases the last 15 or 20 years of life, and that is the part I'd like to get rid of. That is the dream of gerontology and the promise of the biology of aging research."

Link: https://uanews.arizona.edu/story/ua-lab-seeks-holy-grail-gerontology