References: Wikipedia, Eur Jr Appl Phys, Cell Metabolism, Nature, FEBS Press,
Bear with me because this is the crux of aging. Bit by bit, your cells get tired, and senescent. They are still there in your tissue, but they don’t respond to signals and they don’t do their job, whatever tissue they are in. The mitochondria don’t talk to the nucleus and vice versa. Slowly they drift into cell death. You are done. That process shows up with the mitochondria losing their ability to make energy and gradually making more “oxidants”. We have frantically been taking anti-oxidants for decades, hoping that will help. Anti-oxidants soften the blow but don’t wake up the conversation between mitochondria and nucleus in each and every cell. Without that conversation between mitochondria and nucleus the inevitable slide into senescence continues.
That’s the key to reversing aging: waking up that conversation in aging cells (you) between your mitochondria and your nuclei. Now, if you exercise like crazy and induce a shortage of energy in each cell (pushing your muscles and cells to the point of exhaustion – that last pushup, curl, pump, lift) your mitochondria startle, send out help messages to the nucleus, and you start the conversation. That’s why exercise helps. Its effect lasts a few days. You can accelerate that with blood flow restriction training because you hasten the exhaustion of energy supplies. Ditto with Fast Mimicking Dieting: you turn on the conversation between nucleus and mitochondria because you exhaust energy supply and call the internal cellular 911 system. Fast mimicking’s effects last a few weeks to months.
Or, you can use CJC-1295/GHRP2 (Growth hormone inducing peptides). Growth hormone inducing peptides in your body do the same thing as exercise and fasting when it comes to waking up the conversation between your mitochondria and nuclei. What not to like? CJC-1295 is a growth hormone releasing hormone analog. It is a slight alteration of the original hypothalamic hormone but effectively results in the very prolonged release of growth hormone from your anterior pituitary. Your normal process of releasing growth hormone happens when your hypothalamus puts out GHRH (growth hormone releasing hormone) which then stimulates your pituitary to make it. Its use is not without controversy. CJC-1295 was being developed as a drug but one of the subjects taking it had a heart attack and diet. It was “ruled” to have been a random, non-related event, but it killed the clinical trial. Wikipedia refers to the “gray” market for bodybuilding but two minutes on Google will show you a lot more. (The deep dive can get into more detail, but the complexity would put you to sleep…..)
This topic of bringing understanding to the aging process is starting to burrow down into that space: how do we wake up those senescent cells in every tissue in your body? That’s the frontier. Getting a handle on the mitochondria-nucleus conversation has become the key topic. I even found it mentioned in this week’s AARP Magazine titled “Can A Single Pill Keep You Healthy Till 100?”.
WWW: What will work for me? I’m trying to learn this just as fast as I can go. I have now done 5 days of fasting for 14 months in a row and have lost about 15 pounds doing it. I can feel my brain perking up when I do my 5 day fast mimicking thing. And I’m trying to exercise using the 2 mile a day formula with daily pushups and situps. I want to learn the 4 minute high intensity workout, maybe with blood flow restriction. I think I’ll do a column on that (BFR) when I’m off my peptide kick. Am I ready to advise that people use CJC-1295? I want to educate you and me. You are an adult reader and can make your own decision.
- How does your body release growth hormone? Answer: Simple, from your pituitary gland after stimulation by GHRH secreted by your hypothalamus.
- What happens to growth hormone as we age? Answer: We make a lot less. We have the capacity to make more, indeed, but it gets blocked by somatostatin which rises as we age. (I warned you that this dive can go very deep.)
- One of the main problems with loss of growth hormone is what in older cells? Answer: They can’t wake up to do their job, whatever it may be. They slide from quiet waiting (good) to senescence (warning light) to dying (bad, bad, bad).
- You can wake up cells by what central process? Answer: putting stress on the energy supply in the cell: exercise to exhaustion, or fast until glucose is used up and inducing ketones: aka fasting. (You can accelerate this with various tricks: taking oral ketones, restricting blood flow in exercise….or various peptide treatments)
- CJC-1295 was about to be released as a drug and was held up because? Answer: One of the subjects had sudden death from a heart attack.
References: Women’s Health, NY Acad Sci, Wikipedia, You-Tube,
For 5,000 years humans have been touting various aphrodisiacs, to various effect. Most of them don’t work. Rhino horn and tiger’s penis don’t do much for the client, and just kill off precious rhinos. PT-141 works. Really. Read more….
Your hypothalamus/pituitary system make most of their hormones from one precursor protein called pro-opiomelanocortin. There are 11 peptide hormones made off POMC, depending on how you slice and dice it. The melanocortin part of that peptide ends up coding for something called melanotan. That’s what was being researched when they noticed that rats and monkeys that got melanotan all appeared to exhibit more “Sexual behavior”. We can go down the rabbit hole of melanotan another day, but for now, let’s just leave at that being the peptide being studied that started folks researching how they could alter it to increase potency. Melanotan II was meant to be developed for helping folks tan, and thereby reduce skin cancer from too much sun. Nice try. Some folks have been so enthusiastic about a possible tanning agent, that they have used more and more of it, making for too much tanning. Google “too much melanotan” and appreciate the pictures of people who get too tan. And they got turned on. PT-141 is a very simple 7 amino acid chain fragment off melanotan that was made into a circle. That alteration makes it have very high affinity for one of your brain receptors that set off sexual desire. There you have it.
Where does PT-141 fit today? It’s actually been pursued as a drug to give women a boost in their libido. The simplest conclusion would be to say that it doubles the likelihood of women having a “satisfying” occasion. Initial research using it as a nasal spray worked but caused blood pressure to pop up, leading to the FDA putting the kabash on it. In its injectable form, however, we haven’t seen near as much of that blood pressure elevation, and a lot more of the simple arousal effect in men and women. Instead of working on blood flow, it appears to have most of its effect in the brain.
No kidding, it works. Better than Viagra. Better, than Cialis. Better than Tri-Mix. Better than Tiger Penis or Rhino Horn (which have no effect). It works. It can take up to 6 hours before you feel much effect but then may last up to 72 hours. Some folks feel the effect in 15 minutes but not everyone and not reliably. Some folks feel a little hot or flushed, maybe a trace of nausea for the first half hour. The only bad part is that it’s a peptide and gets digested in your stomach. The only really effective way to take it is by injection with an insulin syringe. How much? Probably 1 mg is a pretty good starting dose. Some places say try 1 mg, wait 30 minutes and try a second milligram. I’ve had one report back of 1 mg making one unhappy male unable to sleep on his stomach for a whole night. Had to lay on his back. Too bad, huh!
WWW.What will work for me. I’ve tried every peptide I write about on myself. But here is where I invoke TMI. Boundaries, boundaries. But so far I have over a dozen folks try it and every report back so far has been a “thumbs up”, if I may use a gentle analogy. Better than Viagra, Better than Cialis and “it worked on both of us” to paraphrase one happy client. My conclusion? Someone, please tell the Chinese about this amazing peptide quick while there are still a few tigers. Once you use this, you won’t ever go back. Save a rhino.
- PT-141 does what to women? Answer: Doubles the likelihood of women having a “satisfying sexual encounter”. One of the only effective drugs for women.
- What is it? Answer: It is a 7 amino acid circle peptide that is a fragment of a natural human hormone. It’s not quite natural.
- It works where? Answer: In receptors in your brain, not on blood flow in your tender parts.
- How long does it last. Answer: Some 72 hours.
- Does it have side effects? Answer: A bit of flushing and nausea. The high blood pressure associated with a nasal spray has not been as reliably seen in injections. I could find no reports of having to make an ER visit for too long an effect.
References: CBS News, TransformYou, Self, 4-minute workout,
Want to know the most effective peptide for weight loss? Sure. Don’t we all! AOD-9064 (AOD: Advanced Obesity Drug) is the last 15 amino acids of growth hormone chopped off with a single amino acid added for stability. That’s it. It’s not a natural peptide in and of itself but it is derived from growth hormone. Growth hormone is 191 amino acids long and much more complicated to make. (It also is therefore technically not a “peptide” as the definition of a peptide is under 50 amino acids long.) Growth hormone does have some weight loss effects on its own, along with many other effects. The weight loss component appears to be that tail end.
What are the beneficial effects of AOD-9064? First of all, it has no growth hormone effect, and no effect on blood sugar. That part is good. Fat cells need to be “instructed” to become more responsive to energy demands and give up their fat. Nudging them to do that requires a whole host of activities. You want blood vessels to grow into the fat. You want the fat cell to turn into brown fat that actually get more mitochondria and generate heat. (Babies are born with 50% brown fat to help protect them in those first few hours when their tiny bodies are adjusting to a cold outside world.) But mostly you want tired old cells to start telling their mitochondria to wake and multiply. That’s not an easy task as many older cells are easily nudged into senescence and spiral on down to cell death. For a mitochondria to multiply, it has to get half of its genes from the cell nucleus, but also half from its own DNA. It does that best when there is some “demand” or “stress” put on it. Just like with exercise, you have “no gain without pain”. In exercise, you push your muscles to the point of failure. That last curl, pushup, step is the most important one as at the point of failure is where you gain strength. It’s at that point of failure that the cell internally flips on the switches for mitochondria to wake up and send off their signals to the nucleus and turn on growth. They get the idea that there is no sugar around, so let’s look around for ketones which come from fat. And that turns on getting fat out of your fat cell. That whole symphony kicks off together in one smooth transition.
How can you enhance all that? Actually this is where your “symphony” kicks in. Fasting with fast mimicking diet preps you magnificently. The fasting part is stressing your mitochondria to wake up. Your stem cells multiply, as do your mitochondria. What else rings that wake up alarm? Exercise! And you can do it in 4 minutes with high intensity exercise, or just plain 40 minutes of walking will do it too. Hormone replacement! If you are over 50, men and women need hormones. Just do it, balanced, with human hormones.
Then, start with a GHRP peptide and layer in AOD-9064. 250 mcg twice a day and watch the weight peel off. You don’t feel hungry. Your fat cells open up. And you convert that mushy, lazy white fat to brown fat that burns energy around the clock.
Any one of those by themselves will help lose a little, but so slowly you get discouraged. To succeed, you want to get the whole engine that is your body working at its optimal stage. And then your brain works better too. And that’s the real bonus.
WWW: What will work for me. I’m new at this but the professors I’ve listened to and watched are pretty enthusiastic about AOD-9064. I have one alpha adaptor who has gotten the AOD-9064 but hasn’t reported back yet. I want to understand the key ideas of the physiology first. I’m trying the GHRP right now on myself. I’m doing the Fast Mimicking and pretty close to the exercise target. The 4 minute workout looks pretty awful but I want to give it a whirl. See if I can do that.
- AOD-9064 is a natural peptide? T or F. Answer: Some nuance here. It is naturally a piece off the end of growth hormone but is not naturally in the human body by itself. It’s easier to manufacture when it only has to be 15 peptides long.
- To lose weight, you have to do what? Answer: Far more complex that just eat less and exercise more. We now know that we have to understand the pathways of fat burning and how they get turned on and stay on. As we age, we have to turn on the systems that stopped working years ago. Peptides help do that.
- You can buy AOD-9064 off the internet? Answer: True. However, you get what you pay for. One report from Switzerland (where the Olympic folks want to study and know just what athletes are up to when they push boundaries of legal drugs.) showed that about 80% of internet peptides were below sensible thresholds of purity, or even close to advertised content.
- How do you take it? Answer: Problem here. You have to take it by an insulin needle type shot. Twice a day. Peptides get digested pretty easily in the stomach.
- What is the good source for peptides? Answer: There are compounding pharmacies that will make 99% pure FDA threshold drugs. And it is legal to get them. All that costs more. The AOD-9064 on the market actually exists also. It takes a shot and costs $ 1000 a month.
References: Self-Hacked, Wikipedia, Neuro Endocrin Letters, Bull Exp Med Biol.,
Ready for real shocker! Want to lengthen your telomeres? Do you know what telomeres are? Here we go. (Do you trust Russian research?)
Epithalamin is a peptide found in the pineal gland of calves. It was discovered at the St. Petersburg Institute of Bioregulation and Gerontology by Vladimir Khavinson. It breaks down ever so easily so was altered to the new peptide called Epitalon which is only 4 amino acids long: Ala-Glu-Asp-Gly. This gets digested ever so easily in your stomach so has to be given IV or IM. But note, this is not a natural peptide but a slight modification of the original. That is not to take away from its effects, but this one isn’t natural. It’s just very simple.
What are telomeres? They are the tail ends of your chromosomes that are gradually used up as stem cells duplicate. The protein that duplicates DNA has a certain number of base pairs left inside it when it finishes copying DNA that then gets chopped off the end when it is done. The net effect is that cells can only duplicate so many times. That is called the Hayflick limit. It predicts that humans can only live to be about 120. Extending the Hayflick limit is the Holy Grail of anti-aging. Things like exercise, fasting, good sleep, stress control, less sugar all help extend the Hayflick limit. But not as much as we would like.
This is where Epitalon comes in. This was Khavinson’s first work. He showed that Epitalon extended human fibroblast telomere proliferation from expected termination at the 34th generation up to the 44th generation, making the treated cells have telomeres as long as original cells. Khavinson compared epitalon to epithalamin and found them to be equivalent in effect. And he conducted a prospective human cohort study in humans with 266 folks given epithalamin. Over the next 6 years, there was a 1.6-1.8 reduction in mortality with just one treatment. If combined with another peptide, thymulin, and treated annually, over the subsequent 6 years he reported a 4.1 fold reduction in mortality.
In another study of 79 coronary artery disease patients given 3 years of biannual epitalon treatment they had a 50% reduction in cardiovascular mortality and 28% reduction in overall mortality. These numbers are huge but are based on a tiny cohort. Just one or two deaths would make gigantic changes in the numbers.
Is there a feasible mechanism that explains these potentially huge results? Yes, possibly. It appears that epitalon has the effect of increasing the production of melatonin. Melatonin is a potentially awesome cancer fighter. It also helps you sleep and get better rest. We make much less of it as we age. In one study involving 14 elderly humans, Epitalon improved melatonin back to youthful levels. There is likely also a corroborative effect on the production of T cells, which are cancer fighters. There are now multiple rat studies showing dramatic reductions in cancer spread and size with epitalon. Human studies? Not so much.
Whoa, Nellie! These are over the top, too good to be true studies. And all from Russia. Do we trust the Russians? Is medicine a different forum than election politics? Does the FDA approve? What would you do?
WWW: What will work for me? I have tried every peptide on myself before writing about them. At least so far. I have heard from one of my faculty that he gives epitalon twice a year to all his serious anti-aging clients. (For the last year.). As in, just one year – so no long term experience. What’s a serious, ethical, honest scientist to do? I think every one of us has the right to make our own choices. Doctors have the obligation to first do no harm. To be sure of that, we should be following research-based evidence. Let’s see what research emerges. I’m staying tuned.
- Epitalon is a natural peptide. T or F. Answer: False. It is a modification of epithalamin which is a natural pineal peptide from calves. It has been reported to be equivalent to epthalamin.
- What is epitalon purported to do? Answer: Increase the length of telomeres and increase the production of melatonin. Those two may be linked.
- What has been shown to be the effect of epitalon in Russian elderly folks when combined with thymulin and given twice a year? Answer: An 80% reduction in mortality.
- How much longer do mice and rats live, given epitalon? Answer: Not fair. Not in the note above but if you read all the references: roughly 30% longer lifespans.
- Epitalon is FDA approved? Answer: No.