As human beings age, they become more susceptible to disease, and this happens because of a decline in the immune system. The thymus is a gland that is part of both the endocrine system and the lymphatic system, and the fact that it shrinks with age is one of the primary reasons our immune systems begin to fail. In today’s video, we’re going to examine the biology behind this incredible shrinking gland, and take a look at some research that’s going on into what, if anything, we can do about it. If you want to slow or even reverse the aging process, if you want to turn back the clock on aging… then hit that subscribe button below and subscribe to this channel. Leave a comment and let me know what you think of this channel or suggest topics you’d like me to do a video on. Hit the “Like” button, and hit the “Bell” to be notified when I post a new video. The immune system is incredibly complex and, to be honest, my understanding of it is, in no way, complete. So my explanation of what it is and how it works is going to be simplistic and somewhat imperfect. But that’s not the focus of this discussion. The focus will be on the thymus, how it physically ages and the effects that aging has on the immune system… and on some interesting research that has recently been done to reverse the effects of an aging thymus… and subsequently, restore an aging immune system. The purpose of the immune system is to protect us from infection or illness by being on the lookout for foreign pathogens, such as harmful bacteria, viruses and parasites, or cancerous cells in the body, through a process called immunosurveillance, and then either destroying those pathogens or killing the cells thatthey have entered. It has three components, the skin, which is our first line of defense and acts as a barrier against anything foreign entering our bodies; the innate immune system, which we share with all other forms of life, both plant and animal, and which is responsible for the identification and removal of foreign substances in our bodies, and for activating the adaptive immune system, which is only found in vertebrates, and is composed of highly specialized cells and processes that eliminate specific pathogens through a process of immunological memory. One of the primary components of the immune system are white blood cells, also known as leukocytes. There are 5 different classes of leukocytes. Four of them belong to the innate immune system, and the include neutrophils, basophils, eosinophils and monocytes. Monocytes are made up of macrophages, which consume various pathogens and dendritic cells, which activate the adaptive immune system. While the adaptive immune system is made up of just a single type of cell called a lymphocyte, there are several different types of lympocytes. First, there’s natural killer cells. These cells kill other cells that have been infected by viruses, and they kill cancer cells. They do this by injecting small cytoplasmic granules of protein that cause apoptosis, or cell death. Then there’s B cells. B cells mature in bone marrow and they produce antibodies that selectively bind to antigens. Antigens are the parts of a pathogen that alert the immune system, and antibodies fight infection by
blocking the pathogen from entering the host cell and flagging the pathogen for destruction. And then there are T cells. The “T” in T cells stands for the thymus. They originate in bone marrow, but become specialized, or mature, in the thymus. Their purpose is to recognize antigens that the body has encountered before, and there are several different types of T cells. The first of these are CD4+ helper cells. These cells help activate B cells to secrete antibodies and macrophages. They also help activate CD8+ cytotoxic cells, which is the next type of T cell. Cytotoxic cells are also known as “killer cells”, but they’re still “T” cells and different from normal natural killer cells. However, they still release granules to kill target cells infected by a virus, or cancer cells. Then there’s the naive T cells. These are mature T cells that have not yet encountered their associated antigen. This type of cell is a naive form of helper cells and cytotoxic cells. Finally, there’s memory T cells, which develop when naive T cells get exposed to specific antigens. These cells are trained to recognize specific antigens and to trigger a faster and stronger immune response. All of these different types of T cells originate in bone marrow as precursor cells, then migrate to the thymus to develop into the variety of distinct T cell types. Since all T cells mature and are trained the the thymus, you can see how important the thymus is to this top line of defense. Let’s take a closer look at this gland that’s part of both the lymphatic system and the endocrine system. The thymus is a small, irregular shaped gland that sits just behind the sternum. It’s composed of an outer capsule and an inner true thymic epithelial space, or TES, which is made up of a cortex and a medulla. The space between the capsule and the TES is called the perivascular space, or PVS, and it contains blood vessels that bring immature precursors cells from the bone marrow and take away mature T cells. The cortex and the medulla of the thymic epithelial space is made up of functional thymic tissue, and this is where the immature precursor cells develop and mature into T cells, in a process called thymopoiesis. As we age, the functional thymic tissue begins to shrink. This happens to almost all vertebrates, resulting in changes in thymic architecture and a decrease in thymic tissue mass. This shrinking of the thymus as we age is called thymic involution. It can start as early as the first year and continues throughout our entire life. By age 25, the thymus has already lost 30% of it’s mass, and by the time we reach age 60, over half. A couple of things happen during thymic involution. The functional thymic tissue shrinks at a rate of 3% per year up to about 35-45 years of age, then continues to shrink at a rate of 1% until death. As the thymic epithelial space shrinks, the perivascular space grow in volume. As it grows, adipose tissue, or fat, invades the space, replacing the functional thymic tissue. During involution, the thymus not only decreases in size, but also in activity. As thymic involution progresses, the output of naive T cells declines. These are mature T cells that are responsive to foreign antigens, but have not yet been stimulated by a foreign substance. The ability of the immune system to mount a strong response depends on the receptor diversity of naive T cells, also known as TCR diversity. Naive T cells are thought to be created through a process called homeostatic proliferation, which is the cell division of existing naive T cells. Though homeostatic proliferation helps sustain naive T cell populations, even with severely limited thymic activity, it does not increase receptor diversity. For yet unknown reasons, TCR diversity drops drastically around age 65. Loss of thymic function and TCR diversity is thought to contribute to weaker immunosurveillance of the elderly, leading to increasing instances of diseases such as cancers, autoimmunity, and opportunistic infections. But there is growing evidence that thymic involution is plastic and can be therapeutically halted, or even reversed, in order to help boost the immune system. Just a couple of months ago, in September, the results of a new trial called the TRIIM study were published by Dr. Greg Fahy. TRIIM stands for Thymus Regeneration, Immunorestoration, and Insulin Mitigation. In this study they gave a group of men ranging in age from 51 to 65, a cocktail made up of human growth hormone, metformin, vitamin D, and zinc. And the purpose of the study was to find out if it was possible to regenerate function thymic tissue. They took MRI scans of the thymus at the beginning of the study, and a year later, at the end. And the MRIs showed significant regeneration of functional thymic tissue, replacing the fat which had previously made up most of the thymus. The participants also showed significant signs of immune system rejuvenation. On a side note, they also ran the participants blood through an epigenetic clock called the Horvath clock. The Horvath clock measures the biological age of an individual, compared to their chronological age. Since the study ran for a year, the expectation was that the participants would have added a year to their epigenetic age. But that’s not what happened. On average, each participant had lost a year and a half off of their epigenetic clocks, making them two and a half years younger than they should have been at the end of the study. Now, it’s not known exactly how this happens, whether it’s the result of restoring the thymus or if it’s through the actions of some of the meds that the study group took. But either way, it’s great news for anyone who’s getting on in years. So, while the shrinking of the thymus causes a decline in the immune system which seems to be universal across all vertebrates, it appears that it is possible to regenerate lost, functional thymic tissue. I’ll be keeping a close eye on this, and updating you guys on any progress that gets made in the future. If you enjoyed this video, leave me a comment and if you’d like more, then seriously, think about hitting that subscribe button and subscribing to this channel. Hit the “Like” button, and hit the bell to be notified when I post a new video. Thanks for watching, and I’ll catch you
next week.


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