Thymus aging mitigation strategies
OK time to start thinking about the thymus. First start with this blog post by Josh Mitteldorf (an aging theorist) which is a good introduction to the thymus and aging. The short answer is the Thymus generates memory T-cells ('memory' meaning they remember past exposure to viruses, and T meaning "thymus"). The Thymus gets smaller with age, and we also generate fewer T-cells. From the post, we don't know why the Thymus shrinks, except that it is not from typical aging senescence.
One way to increase its size (presuming that larger = better) is possibly through human growth hormone (HGH). Supplementing with GH comes with a host of other problems - at the moment it's best not to attempt this. In the comments the author, who is a friend of Greg Fahy's, discusses Gregs 1 year experiment with HGH. At the end he did have a larger thymus
So AFAIK we don't know yet how to fix the root cause of aging thymus degeneration, but we do know (clinically verified in many studies) how to mitigate the result which is poor T-cell function. In this way we can address the effect, if not the cause, similar to addressing failing adrenal function by hormone supplementation. This is something I've mentioned here several times, because it surprises me that it's not bigger in the aging community, bu which is 3+ day water only fasting. There's a lot of top drawer research behind this, the most approachable is to read The Longevity Diet by Valter Longo who is one of the primary researchers, working at UCLA. No he's not trying to make a buck, I think all the money goes to a research foundation, he's reporting on his work which started as a PhD student working for Roy Walford.
Roy believed that long term calorie restriction prolonged life, but now we know that unfortunately it does not. Aubrey DeGrey frequently cites this, it turns out that chronic calorie restriction in long lived species does not confer the same benefit it does in short lived species. We can hypothesize about this from an evolutionary standpoint, but regardless it's an established fact. Now Valter continued Roy's work and has found that instead of chronic restriction intermittent calorie restriction does have tremendous benefits. Far more that what many of us are doing here via pharmaceuticals and nutraceuticals.
It's spelled out in that book, but back to the topic at hand, at around 3-4 days of a water only fast what happens is about half of our T-cells are killed off. These are old programmed T-cells hanging around, after a lifetime of exposure we have this old programming still around. But what happens is when you re-feed (start eating again), your stem cells (which enjoy a rejuvenating effect) regenerate those T-cells, but now they're baby unprogrammed cells. So - stem cell therapy, simply by not eating for a few days.
If anybody is interested we can discuss why's and how's. I do it - been doing water only fasts for years, twice a year which coincidentally what Valter recommends for those with 'elite health'. Anecdotal evidence of it's benefits; since I started I haven't gotten sick. Not once. Used to get sick every year, but no longer. I attribute this to probable T-cell rejuvenation which is more responsive to infection. Note there are many, many other benefits too, which Bill Faloon recently reiterated in lecture.
I would recommend for everybody here to deeply consider adding multi-day water only fasting to their regime. It's the cheapest, simplest, easiest, strongest with no side effect way to improve longevity.
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Question:
If you clear half of your old T cells and later replace them with new ones, does that mean that you may lose immunity to past diseases that the old T cells "remember"?
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JGC Great question - one I've wondered about. In practice the answer appears to be no. Over the years of doing this I've ceased to get sick. This occurred before I started NAD/Metformin and the like, so it appears to be more related to the fasting/lifestyle than the latter. But while everybody around me has been getting sick normally, for me (knock on wood) the last time was maybe five years ago.
Why? No idea, but some thoughts. Perhaps we have multiple T-cells programmed for the same thing (redundancy), so we're just clearing out the excess. Or, perhaps these old strains are already gone from the environment, or something else. Or it could be that if you replace the old ones with fresh, they can just as easily re-print if they need to. Otherwise I don't know.
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hello Dan ,I go to perpetual life church and go to raad fest yearly. I have just joined the group. can you call me sometime today please 704 491 5558
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Dan, mostly great post, but I think you have slightly mischaracterized a few important things....
Dan said:
it turns out that chronic calorie restriction in long lived species does not confer the same benefit it does in short lived species. We can hypothesize about this from an evolutionary standpoint, but regardless it's an established fact.I don't think this is settled science to the point of wide agreement as you suggest. Aubrey & most of the SENS community, including Reason of FightAging.org certainly believe that CR confers minimal benefit to humans as you say, and I agree. But it's important to note that many aging scientists still believe there is a possibility for much bigger benefit from CR or its mimetic drugs. This is important because if the issue were more settled, it would likely effect amounts of research funding flowing to different subparts of the field.
Also notable on this issue is Michael Rae for being both a CR practitioner and one of the staunchest defenders of the idea that human CR is worthwhile but also squarely in the SENS community (co-author of Ending Aging with Aubrey, and officially the SENS science writer). He is a very well-informed guy who knows the literature and the arguments on both sides.
One of the most interesting places to read some of the debate on this topic is on the CRSociety's own web forums where several practicing members of that community discuss relatively recent evidence suggesting weaker overall human benefit in a thread called https://www.crsociety.org/topic/11699-will-serious-cr-beat-a-healthy-obesity-avoiding-diet-lifestyle/
As for Intermittent Fasting, I completely agree that it is probably a great thing for long-term health for most people, but I think it might be implying too much benefit to make it the focus of a thymus regeneration thread. It's true that Longo's work showed elimination of WBCs from long enough fasts and that WBC count recovers at least somewhat on refeeding, but I don't recall seeing any demonstration (your n=1 anecdotal data aside) yet of improved infectious disease resistance or any biomarkers for overall immune system function showing long-term improvement (though admittedly I don't follow that literature closely). And it's also true that organs shrink on 4+ day fasts and recover size on refeeding, but I'm not aware of any demonstration of the thymus getting bigger than before a fast. I've also heard some people worry about stem cell "exhaustion" as a potential long-term problem if they are called on to regenerate new WBCs too many times---I think this goes into the category of no one knows yet if that's a problem.
Longo himself often presents one of the main benefits as getting a fraction of the CR benefit but in a way that is easier to do. So of note I'm not sure how valuable IF is for those already very healthy or even doing CR. Most of the scientific data on IF uses controls that are typical humans eating mostly pretty bad diets or ad-lib rodents and thus the results don't speak to the level of benefit from a healthier starting point. I think one of the main benefits of fasting is from its anti-cancer properties (cancers like glucose and don't like ketones, plus they like protein especially met & cys) and likely senolytic effects (but this area needs more research).
And of course, in the category of nice to know about but doesn't help what people can do themselves now, Reason himself now has a startup called Repair one of whose research programs is thymus regeneration, which he's talked about on FightAging.
Karl
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I think Greg Fahy presented results of his TRIIM trial at the last LEAF meeting (I guess this is hGH+DHEA+metformin):
Greg Fahy – Intervene Immune, Intervene Immune: Reversing human aging right now!
https://www.leafscience.org/2019-program/
https://www.leafscience.org/rejuvenation-roundup-july-2019/
I guess it is due to preprint and publish soon. I heard results are promising. Anyone here knows more and have more information?
Thank you.
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Results of TRIIM triay by Dr Greg Fahy are out and are encouraging !!
https://www.nature.com/articles/d41586-019-02638-w
Cannot open https://doi.org/10.1111/acel.13028 though ...
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albedo
Here is the paper (as a link in Dr Josh Mitteldorf's great blog on the TRIIM results):
https://drive.google.com/file/d/0B97CJJ5YOfctalRfZExnd2lHUmRyYUNWMFZYMUgzSXJKVzg4/view
"...Treatment consisted of
- Human growth hormone (HGH), 0.015mg/Kg body weight, adjusted individually according to metabolic response. HGH doesn’t survive digestion, so it is self-injected with a tiny needle in the belly
- Metformin, 500mg daily
- Vitamin D, 3000 IU daily (5 times RDA)
- Zinc, 50mg daily (5 times RDA)
- DHEA, 50mg..."
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So what do you think of this TRIIM trial? Their http://interveneimmune.com page is not very convincing, to be honest. One TRIIM trial volunteer is a CFO of the company, etc. But I am still hopeful, of course! Glad that they published the dosage, now everybody can start experimenting!
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I do not agree with "multi-day water-only fasting." I am GUESSING that it is BAD for your good health and causes damage to your body because you did not give your body the nutrients that it needs to repair itself if necessary.
If you would like to convince yourself if I am right (or wrong) just take a look at BEFORE and AFTER pictures of THE FACE of persons who have done a water-only fast... even a "short" 5 day water-only fast... and much more dramatic, a longer (eg. 20 day) water-only fast.
I AM in favor of "fasting" but I am NOT in favor of "water-only fasting" longer than ONE DAY.
Our body needs: WATER-CALORIES-FIBER-VITAMINS-MINERALS-OIL (fat)-PROTEIN. Those are the minimum requirements.
So... you should "almost water-only" fast.
Give your body water, and at least 500 calories per day (may come from protein or fat or carbs), fiber, vitamins and minerals, oil (fat), and protein.
(memorize: "wa-cal-fi vi-min-o-pro")
Note that oil (fat) and protein are required, carbs are not required but can be part of your 500 calories.
For example, lettuce and tomato give you some carbs, some vitamins and minerals, and fiber. One egg gives you vitamins, minerals, protein, and fat, and zero carbs (which is fine...)
So a decent and healthy "almost water-only fast" is all the water that you wish, plus lettuce and tomato and eggs. Add a squeeze of lemon. Drink a multi-vitamin-mineral if you wish. Have some no-sugar gelatin (protein and water).
Note: I am not a doctor, and I never studied a day of nutrition in any school.
So don't listen to me if you don't want to.
But take some good photos of YOUR FACE before you start a water only fast, and take some good photos of YOUR FACE after you end a 5 day or longer water-only fast.
Please show them to us, and we can all vote on whether or not your face shows it has aged, before and after.
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Dan said:
One way to increase its size (presuming that larger = better) is possibly through human growth hormone (HGH). Supplementing with GH comes with a host of other problems - at the moment it's best not to attempt this.I am not aware of the "host of other problems" that come with supplementing with HGH at a physiological dose. Can you please tell us what are those other problems?
note: I have had a dose (mostly, 2 units per day: .67 mgs) of authentic injectable Human Growth Hormone almost every day without fail since June, 1998... that is now more than 21 years. So please tell me about the host of other problems I have not yet seen.
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Korean Ginseng prevents thymus involution: https://www.mdpi.com/1420-3049/25/7/1492/htm
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Fahy's TRIIM 2 study is supposed to start around the beginning of 2021. To participate in the trial, without subsidies, is over $10K. Is anyone considering self-experimenting with the TRIIM 1 protocol?
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On the subject of enhancing T cells, I read an article the other year that people who slept in a room with Hinoki Cypress oil in the air had enhanced killer T cell count for a week afterwards. I can only say that having tried it I didn't have access to bloodwork but my lymph nodes were indeed swollen after sleeping in a room with the oil diffuser.
I found an old paper on the subject but there should be something kicking around from 2019 too.
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Watched a video of Greg Fahy on Modern Lifespan YouTube channel . He appears to be much younger than previous images and he has been doing his HGH protocol since 2013. His first TRIIM trial results were pretty impressive in regards to reversing epigenetic age of the participants.
In addition to fasting, sauna therapy seems to trigger release of HGH.
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The lesser known counterpart Epitalon, was Thymalin. Which was deemed important to rejuvenate the thymus way back when these russian peptides were being developed. I wonder how the trim protocol compares to thymalin and also what would happen if you combined the two and added thymalin into the trimx protocol.
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Fred Cloud exactly, i have no idea why they choose metformin instead. they should have picked thymalin/thumalin with hgh n vitamin A
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Burgundy Summer It turns out alot of those other compounds in the trimx protocol were chosen to deal with side effects from the HGH itself. Mainly the insulin resistance, so hence the metformin and the fahy found the dhea helped too. He theorized that people have high hgh when they are young and they dont have insulin resistance problems but older people who take hgh do. So he figured it was the difference in dhea levels.
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AIUI Melatonin stimulates more HGH I wonder if that has an effect on the Thymus.
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Very interesting. I am not excited by the TRIIM trial but may be at the end of 2024 - early 2025 when the women's TRIIMX trial will apparently be completed.
Re water fasting. I tried this after learning I have immune senescence. The immunologist - for reasons unknown - then misdiagnosed me with CVID - a disease diagnosed by the patient's constant catching of everything around. I haven't had a cold since 2014, or flu since 1995, and was neither jabbed nor caught the most recent virus doing the rounds. I don't get skin infections or pink eye.
This said, I am always looking for something to improve my senescent immune system. I have very low naïve T-cells and certain immunoglobulins. So I water fasted for two days, got a terrible migraine and passed out twice. Definitely not for me.
A few companies make "natural" HGH analogue supplements, e.g Source Naturals' HGH Surge. Does anyone have experience with these? Are they, in your opinion, worth taking?-
Moonlitnight Have you considered Rapamycin for immune senescence?
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I haven't, Steffan. I guess I am still hung up on the "rapamycin can promote cancer" thing. Due to the senescent T-cells, including NKs, I don't want to tempt fate. My entire family, including three much-older sisters, died from cancers including a rare gallbladder cancer. My parents are first cousins.
This said, Dr. Gabrielle Lyon, a protein-loving weight trainer, says there is no science-backed indication that stimulating mTOR induces cancer. So I find the whole topic a little confusing. My internist suggested I start consuming more protein and lifting weights again when I showed him a paper showing the breakdown of skeletal muscle coincides with the breakdown of the immune system in older people. Together, we pulled up a couple more papers. I said I hadn't done this as I didn't want to stimulate mTOR and end up increasing my already high risk of developing cancer but his feeling was that the possible immune benefits might outweigh the pitfalls of stimulating mTOR. I asked him about rapamycin during this convo (I live in Canada) and he said he had looked into it as many of his peers were taking it. However, he wasn't keen and I have no way of getting my hands on it.
I started lifting weights again (I stopped in my late 30s) and in two weeks was lifting the same weight as I did when I was a gym-rat, so I don't think muscle breakdown was contributing to the immunosenescence! I am now lifting even more. All this is puzzling to me and to my internist. I am a skinny thing and am slinging heavy weights around again. It's not muscle memory because that only lasts three or four months max, not three decades. I am focusing on the positive but the awful words of the immunologist "You could catch something and die if you don't infuse yourself with human plasma every week for life" keep ringing in my ears.
Thank you, Steffan. I am going to do more research.-
Moonlitnight . Most research indicate that mTOR inhibition is a way to improve the function of the immune system in older persons. that is done by taking low dose once a week. (5 mg)
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Moonlitnight I share your caution regarding rapamycin, Moonlitnight. There is so much current research on rapamycin, and perhaps more importantly, on the probably superior rapamycin analogs ("rapalogs"), that our patience in waiting for the results of these studies seems quite prudent at this point.
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Has anyone tried NIR light therapy for thymic involution? Dr. Michael Hamblin, an older Harvard Prof. who has authored 450 papers and specializes in photodynamic therapy, has said during an interview that NIR stimulates the immune system. He has also suggested that NIR therapy from panels giving out the correct power and wavelengths should be directed to the thymus. Many of the red light therapy companies' panels fulfil these requirements and I am using a panel myself (just started last week). I sit close enough to it (12") to direct the NIR to my thymus. Whether or not it will stimulate my immune system remains to be seen, but I will get my blood tested in six months.
I have read enough studies to feel NIR can have a real impact on aging bodies, so fingers crossed.-
Moonlitnight A very long interview, but full of the most up-to-date information about rapamycin. At 1.26.40 they talk about the rejuvenation of the immune system. But then again every person has a unique biology and might respond uniquely.
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