Reverse Thymus Aging Part IIMay 15, 2022
Live Longer by Reversing Thymus Aging - Part II
The TRIIM (Thymus Regeneration, Immunorestoration and Insulin Mitigation) Trial caused a lot of excitement when it came out. The first study in humans to show a reduction in the most accurate clock of biological age, our epigenetic clock. The 9 volunteers had a 2.5-year reduction in their age on measuring epigenetic age from the study protocol taken for one year. The Protocol was simple: Growth Hormone, DHEA, Metformin, Vitamin D, and zinc taken for one year with MRIs of the thymus gland to watch its regrowth and serial blood testing to monitor immune response.
Aside from increasing the size of the thymus gland, there were remarkable changes in immune functions that are worthy of note. There was an increase in the production of new T-cells, a core process of a fully mature function thymus gland that decreases with aging. They also documented three classes of new or “naïve” T-cells that increased. Because new T-cells survive and function for years, then these new T-cells (immune traffic cops) will continue to protect after being turned on. That increase could be monitored by measuring the Lymphocyte to Monocyte Ratio: LMR. It increased. There are many studies that demonstrate a reduction in cancer and all-cause mortality with an increased "LMR" ratio.
What is it about monocytes? Well, most of them carry an enzyme called PD38 that degrades NAD. Aha! The link with your epigenome. NAD is the fuel that sirtuin proteins must have. Degrade NAD and your sirtuins won't work. Your sirtuins are the caretakers, the gardeners if you will, the lifeguards of your epigenome. They depend on NAD for their energy supply. More monocytes, less NAD.
It wasn't just immune function as measured by LMR that tipped. The study showed a pretty dramatic improvement in cancer protection by stimulating a reduction in PD-1 expression on cytotoxic T-cells. The PD-1 receptor is used by many cancers to trick your immune system to giving the cancer cell a pass. With that receptor, the cancer keeps growing right under your immune system's nose. The heavily advertised drugs, Keytruda and Optivo, both work by blocking the PD-1 receptor.
Finally, they also showed that the PSA, free PSA ratio all improved quite dramatically: PSA dropped and Free PSA increased. Again, a reduction in risk.
All of these effects are broad-based in their impact and have important implications for overall health. You can summarize it down to just a few key talking points. 1. ) This strategy increases your thymus gland function of manufacturing youthful, active lymphocytes, changing the LMR (lymphocyte to monocyte) ratio.
2). Too many monocytes are not so good for you because they gobble of NAD.
3). You really do need NAD to maintain a youthful epigenome and turn on the right genes when they are needed, and turn off the wrong genes when you don't want them - actions that require NAD. 4). You turn off PD-1 and that doesn't let cancer out of the bag. Keytruda is not cheap. Cancer is not friendly. You want less PD-1.
www.What will Work for me. I've got it. The link between NAD and David Sinclair's brilliant book,Life Span, and immune function comes to focus. We should all be on NAD and Metformin, DHEA, zinc, and Vitamin D. Now, Growth Hormone is pricey at some $ 2500 a month but CJC/Ipamorelin isn't so expensive. The challenge is to get these markers available to us ordinary folks so we can keep ourselves "younger" and measure it to prove it. MyDNAge.com does a pretty good job of telling you your epigenetic age if you want to measure it.
References: Aging Cell, Life Extension, LifeSpan,
1. What is your epigenome? Answer: the markers on the outside of our chromosomes that manage the expression of our genes. We pass many of those markers on to our kids, so the epigenome acts somewhat like your genes as an intermediate layer. It is managed by your sirtuin proteins, that run on NAD only.
2. What happens to your epigenome with the TRIIM protocol? Answer: In one year of following the TRIIM protocol, your epigenome gets 2.5 years younger.
3. That beneficial effect is modulated by several synergistic effects. Can you name several? Answer: a) Increased thymus size (last week's letter), b) Increased fresh new T cells, c). Improved Lymphocyte/Monocyte Ratio. d). Reduced PD-1 receptor activity e) Increased NAD, f) reduced PSA and increased free PSA, g). reduced CRP.........
4. What is the link between thymus aging and your genetic resilience? Answer: When you make fresh, young T cells, your monocytes decline and they tend to degrade NAD. With more NAD, you have the fuel to keep your sirtuin proteins energized, and they take care of your epigenome, and keep it functioning vibrantly and protectively.
5. Can you name the compounds/elements taken in the TRIIM trial? Answer: Growth hormone, metformin, DHEA, Vitamin D and zinc.
This Column was written by Dr John E Whitcomb, Brookfield Longevity, Brookfield, WI (262-784-5300)