The Organ That Controls How Fast You Age

When people talk about the organs that matter for longevity, they'll mention things like your heart, brain, kidneys and maybe the liver. But there's one organ that almost nobody talks about, even though it might be one of the most important organs for your aging overall, is the thymus. A small organ sitting behind your breastbone and in front of the heart. The thymus is responsible for training and regulating much of your immune system, and unlike your brain or heart, it starts aging remarkably early, already after your puberty. This process is called thymic involution, and it's one of the main reasons your immune system function declines with age. As the thymus shrinks, your body becomes worse at producing and maintaining the immune cells that protect you from infections, cancer, and many other age-related diseases. So in this video I'm going to break down why the thymus matters so much for your longevity, what thymic involution does to your body, and whether there are any ways to slow down this process or reverse it. The thymus is a primary lymphoid organ of the immune system, which means that it's one of the Its main role is to not filter lymph like a lymph node, but to mature and train T-lymphocytes, which are a type of white blood cell, so that they can function properly in immune defense. These T-cells are critical because they help fight infections, coordinate immune responses, kill infected or abnormal cells, and help the immune system learn what belongs in your body and what does not. Now here's the problem. Your thymus starts shrinking as you get older, which is called thymic involution. 70-year-olds have less than 10% of their thymic size since they were born, and that thymic tissue is being replaced with fat tissue and perivascular space. Thymic tissue is at roughly 95% in newborns, about 60% by age 25, and 10% or less by around age 70. So at older ages, most of the active thymic tissue has already been lost. The structure of the organ becomes more disorganized and its ability to produce new T-cells drops. This is not something that suddenly happens in old age. It already starts relatively early and continues gradually over decades. The consequences of this are huge. Thymic involution contributes to what's called immunosenescence or aging of your immune system. It weakens your response to infections and also increases the risk of developing cancer. It has been seen that higher thymic health is associated with better survival over time. In the NLST cohort, 12-year mortality was 13.4% in the high thymic health group versus 25.5% in the low thymic health group. They also had lower incidence of cancer and lower cancer mortality. After 6 years, those with high thymic health had a 3.4% incidence of lung cancer compared to 5.3% of the low thymus group. The lung cancer mortality was also lower, 1.1% versus 2% of absolute risk. Removing the thymus has striking consequences on not only immunity but overall longevity. In a 2023 paper, over 1100 adults who underwent thymus removal during cardiothoracic surgery were compared to 1100 controls with a mean age of 55. The surgical removal of the thymus was associated with a 2.9-fold higher risk of all-cause mortality, about double the cancer incidence, 1.5-fold increase in cancer mortality and 1.5-fold increase in autoimmune disease. But this doesn't happen to only people who get their thymus surgically removed. What happens reveals what's going to happen to all of us as we get older, when 90% of our thymus has shrunk. The thymus shrinks with age because the tissue that helps train T-cells slowly wears down. The cells that support T-cell development such as IGF-1 and FGF-21 decline. The structure also becomes less organized and more of the thymus gets replaced by fat. Aging also increases stress and inflammation inside the organ, which makes it function worse. Pro-inflammatory cytokines increase with age and they damage the thymus. A quick word from today's sponsor, OneCharge. One of the things I use for skin health is red light therapy and there are actually some pretty interesting clinical trials behind it. In a 2023 randomized split-face trial of 137 women, researchers treated one side of the face with 660 nm of red light and the other with 590 nm of amber light for 10 sessions over 4 weeks. Both reduced wrinkle volume around the eyes by about 30%. And this was a split-face trial, which means that only one side of the face got the treatment. Another 2023 study had women use a 630 nm LED face mask twice per week for 3 months. The researchers measured wrinkles, firmness, elasticity, dermal density, skin texture, and other markers. What they found was progressive improvements in visible signs of skin aging. And mechanistic research using human skin cells and skin tissue has found that combining 640 nm of red light with 680 nm of near-infrared light increases the production of collagen and elastin. That's because these wavelengths of light reach deeper into the skin, unlike other wavelengths of light that hit the surface layer, such as blue or green light. So the wavelengths of the device actually matter. I personally use the BondCharge LED face mask, which gives you red and near-infrared light in an easy mask you can use at home. If you want to check it out, head to bondcharge.com forward slash seamlunt and use the code SEAM for 15% off. A very interesting reason why the thymus shrinks with age, especially in men, is sex hormones. Sex hormones seem to be one of the reasons thymic involution speeds up after puberty. Endogenous androgens like DHT and testosterone have potent effects on atrophying the thymus. So as your sex hormone levels increase after puberty, they appear to push the thymus towards shrinking and lower T-cell production rather than growth. The biggest sex hormone responsible for this is DHT or dehydrotestosterone. DHT suppresses thymic output of new T-cells and accelerates thymic involution. In one 2011 paper, it was seen that hypogonadal men with clinically low testosterone had higher markers of recent thymic output, and testosterone replacement therapy lowered these naive T-cells and T-rex, which suggests that restoring their androgen levels reduced their thymic activity. Androgens have immunosuppressive and pro-clotting effects, which could explain the increased risk of heart disease and cancer in men. Men have 10 to 18 times more testosterone in the blood than women, and the immunosuppressive effects of testosterone appear to be weaker in women than in men. Indeed, it's seen that females between ages 20 to 62 have significantly higher blood markers of newly produced T-cells that leave the thymus. This difference stays significant after the age of 30 and 40, but it becomes less obvious at higher ages. Now, androgens have some benefits. They can help to restrain overactive immunity, but that comes with a trade-off. The same androgens also reduce thymic regeneration and contribute to fewer T-cell production over time. Women obviously also lose thymic function with age, but usually much slower than men. After menopause, the sharp fall in estrogen has been shown to briefly reduce hormone-driven thymic suppression and allow some transient thymic rebound, but the evidence for that is still not definite. Now, this is a great example of what's called antagonistic pleiotropy. Things that are beneficial for reproductive success early in life aren't necessarily beneficial for maximal lifespan. Having high sex hormones like high DHT in early life obviously improves reproductive success. As an organism, you're going to perform very well in the first three to four decades of your life, but at the same time, these same sex hormones accelerate thymic involution, which speeds up immunosenescence and shortens maximal lifespan. Now, obviously, you don't want to deliberately try to suppress your DHT or other sex hormones, because there's a lot of other things you can do to maintain good thymus health. Before I talk about more advanced therapies, here are the fundamentals that you want to focus on. Stay lean and avoid obesity. Obesity is a factor that exacerbates age-related thymic involution, so maintaining good metabolic health is one of the most practical ways to reduce pressure on the thymus. Calorie restriction may help. The evidence does suggest that calorie restriction can slow down age-related thymic involution. You want to reduce chronic inflammation. Molecules associated with thymic degeneration include various inflammatory proteins, and inflammation tends to increase with age. Oxidative stress also matters. Cells of the thymus are quite vulnerable to oxidative damage, because they produce very little catalase, which is an antioxidant. This allows hydrogen peroxide to accumulate and contribute to the atrophy of the thymus. And lastly, don't assume that more sex hormone signaling is good for the thymus. Sex hormones, especially androgens and DHT, can promote thymic atrophy and involution. Now, I want to talk about some potential research on various peptides and therapies that could help to maintain thymus health. Thymosin alpha-1 is one of the more promising peptides. Early clinical trials and clinical data suggests that it can restore immune function in aged or immunosuppressed individuals, as well as reverse functional signs of immunosenescence. Thymosin alpha-1 targets the thymus gland, which regulates immunity. However, thymosin alpha-1 hasn't been shown to reverse thymic involution. So yes, it can help with immune function, but it might not be enough to reverse thymic involution. Thymosin alpha-1's synthetic version, thymalphasine, is clinically approved in some countries for certain infectious diseases. It also reduces mortality in sepsis and other infections. Epitalin is another peptide that usually is associated with brain health, but people also think that it might help with the thymus. However, there are no published papers on thymic involution or thymic function using epitalin. There are some reports from Russian studies done by the creators of epitalin, but these studies are generally very poorly conducted and weak. I made a separate video breaking down the reasons if you want to check it out. Epitalin does increase melatonin production in older age. Interestingly, melatonin supplementation has been seen to reverse age-related decline in immune function by restoring cell proliferation and DNA synthesis in the spleen and thymus of old rats. In humans, age-related decline in melatonin production has been observed alongside a decline in thymic endocrine function, as measured by FTS teeters. However, in this study, it was a correlation, so it doesn't prove that lower melatonin causes the thymic decline. But melatonin is still especially relevant because the thymus itself can produce small amounts of melatonin, and melatonin regulates the immune system. In human clinical research, melatonin supplementation has been seen to reduce inclinatory markers, as well as support immune function. When it comes to melatonin and thymic regeneration, then it just hasn't been studied yet, because the measuring requires an MRI and it's quite expensive. But in mice and rats, melatonin supplementation does appear to support thymic The closest we've ever gotten to thymic rejuvenation in humans, as measured by an MRI, is what's called the TRMM protocol by Dr. Gregory Fahy. TRMM stands for Thymus Regeneration, Immunorestoration, and Incident Mitigation. In the original TRMM study, middle-aged men were treated for about a year with recombinant human growth hormone plus DHEA and metformin. The idea was that growth hormone stimulates thymic regeneration, because growth hormone can support thymic epithelial cells. DHEA and metformin are used to offset growth hormone's harmful effects on insulin sensitivity. Chronic growth hormone use can increase insulin resistance. What the trial found was that, based on MRI evidence, some of the thymic fat was replaced with regenerated thymic tissue, and they also saw some improvements in immune markers, as well as a decrease in several epigenetic age estimates. It's one of the few studies that actually tried to reverse thymic involution, but this study is still in its early stages. And it was a small study and it was uncontrolled. There's also what's called rankle treatment, where researchers give exogenous rank ligand to restore the signaling pathway that weakens with age inside the thymus. In aged mice, this rebuilt thymic architecture, increased both endothelial cells and thymic epithelial cells, improved the entry of T-cell progenitors into the thymus, boosted new T-cell production, and even improved vaccine and antitumor responses. The interesting part is that the study showed rankle could stimulate human thymic cells in organ culture, which makes the idea quite plausible in humans. But again, this study is quite experimental still. The most important message of this video is that the thymus is one of the hidden control centers of aging, because it helps to regulate your immune system and keeps your body capable against new threats. Unfortunately, right now, there are no proven ways to regenerate the thymus, but there are some things you can do to slow down its involution. The good news is that there are some therapies that are being investigated, such as the TRMM protocol or rankle protocol, but it's going to take a little bit of time before we actually get some real evidence that they work or not. Alright, thanks for watching. If you want to discover your health percentage and get your roadmap to top 1% of health, then join the community using the link in the description. I'll see you there.