Drugs Rejuvenate the Body’s ‘Epigenetic Clock’ to Reverse Some Aspects of Aging

A small clinical study in California has suggested for the first time that it might be possible to reverse the body’s epigenetic clock, which measures a person’s biological age.

The antiaging trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin.

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.

Scientists construct epigenetic clocks by selecting sets of DNA-methylation sites across the genome. In the past few years, Horvath — a pioneer in epigenetic-clock research — has developed some of the most accurate ones.

The latest trial was designed mainly to test whether growth hormone could be used safely in humans to restore tissue in the thymus gland. The gland, which is in the chest between the lungs and the breastbone, is crucial for efficient immune function. White blood cells are produced in bone marrow and then mature inside the thymus, where they become specialized T cells that help the body to fight infections and cancers. But the gland starts to shrink after puberty and increasingly becomes clogged with fat.

Evidence from animal and some human studies shows that growth hormone stimulates regeneration of the thymus. But this hormone can also promote diabetes, so the trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, in the treatment cocktail.

The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age. It was led by immunologist Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, and was approved by the US Food and Drug Administration in May 2015. It began a few months later at Stanford Medical Center in Palo Alto, California.

In 1986 Fahy read a study in which scientists transplanted growth-hormone-secreting cells into rats, apparently rejuvenating their immune systems. No one seemed to have followed up on the result with a clinical trial. In 1996, he treated himself for a month with growth hormone and DHEA, and found some regeneration of his own thymus.

In the TRIIM trial, the scientists took blood samples from participants during the treatment period. Tests showed that blood-cell count was rejuvenated in each of the participants. The researchers also used magnetic resonance imaging (MRI) to determine the composition of the thymus at the start and end of the study. They found that in seven participants, accumulated fat had been replaced with regenerated thymus tissue.

Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests.

The effect persisted in the six participants who provided a final blood sample six months after stopping the trial.

Written By Brian Wang, Nextbigfuture.com

33 thoughts on “Drugs Rejuvenate the Body’s ‘Epigenetic Clock’ to Reverse Some Aspects of Aging”

  1. Goat’s Rue may give at least some of the Metaformin benefits. The fact that it’s been available for centuries keeps it from being endorsed by big pharma.

  2. Or binge watch Netflix and take 30 extra seconds during my bathroom break to pop some pills?

    Which do you think more people will do?

  3. So make hay while the sun is up as the saying goes.

    This trial didn’t have to run that long to get a result. If and when the law changes, flush the remainder. Ibutamoren is very cheap (at doses to just boost GH 40% but not the dosages to say cheat at professional tennis) so not a financial risk concern.

  4. Since I know a few things you’ve cited have only been demonstrated in rats, I’m inclined to think that a lot of things you’re citing have only been demonstrated in rats.

    By the way protein fasting is an extremely bad idea, do not do that.

  5. Ibutamoren is a pseudo controlled substance, it will banned if the SARMS Control Act ever gets out of committee (despite being a GH secretagogue, it is named specifically in the bill); and metformin is controlled. The only one easily accessible is DHEA.

  6. GH injections give a high concentration with a steady decrease in time. The exposition to high GH concentrations is much longer. This is why Egrifta has much lower side-effects than GH injections.

  7. The key with Tesamorelin (Egrifta) is the fact that it stimulates the natural pulsatile secrection of growth hormone by the pituitary gland. The pulsatile element is the key here. It means that high serum concentration of GH during a 24 hours period is short. Look at figure 1 in this article.

  8. Before everyone starts taking drugs to live forever they should start with Intermittent Fasting and getting some sun and exercise. Once on that path, age therapies can be applied. Metformin and the new drugs to clear senescent cells are a good start.

  9. Reducing and addressing AGEs Advanced glycation end-products, I think is a nobrainer. That stuff has been implicated in diabetes, atherosclerosis, chronic kidney disease, and Alzheimer’s disease.
    They are in food and the body can make them too. I select my foods and ingredients carefully to avoid high levels. And I take supplements that help get rid of this junk.
    It makes a lot of difference how you cook and how you mix ingredients as well. You don’t want to beat anything very much with fats and sugars, or proteins and sugars. If you really like whatever it is try to do all the heavy beating before the fat/protein and sugar are in there together. Add whatever at the last second. Cooking should be at low temps if carbs are with either protein or fat.
    Butter is a big no no. Anything fried is bad. Avocado oil and pistachio oil are ideal. Olive and canola are not so good. If you want the olive antioxidants just just buy those. https://www.medicalnewstoday.com/articles/324878.php

    Healthy kidneys do process and remove most AGEs. One it does not, and the crap accumulates and causes lots of problems: Glucosepane. We have nothing you can take to get rid of this crud. That is why it is a no brainer to reduce the accumulation of this in the first place. They may come up with a treatment…they may not. Or it might take decades.

  10. HIIT (high intensity interval training): https://www.sciencedaily.com/releases/2017/03/170307155214.htm
    Nicotinamide Riboside (a NAD+ booster)
    (I invested in CDXC the manufacturer) We know NAD+ levels fall with age, and we know this supplement can raise levels dramatically in humans. But, thus far, the evidence of antiaging benefits in humans is very limited. It may simply improve sleep or make other less dramatic improvements. It probably reduces inflammation…which may be sufficient reason to take it, as the common NSAIDs pain relievers have side effects that may be worse than suspected. NR is unlikely to do any harm. Anecdotal claims say it helps reduce the time needed for muscle strain healing. A lot of people claim it gives them energy https://www.amazon.com/TRU-NIAGEN-Advanced-Nicotinamide-Increases/dp/B01IMF8D2Q/ref=sr_1_5?keywords=Nicotinamide%2BRiboside&qid=1567877866&s=gateway&sr=8-5&th=1#customerReviews

  11. Stress reduction and positive outlook can certainly help. Lower blood pressure, more healthy neurotransmitter balance, less stress chemicals in the bloodstream: norepinephrine, adrenocorticotropic hormone, adrenocortical hormone, cortisol and adrenaline. Stretching and balance exercises can reduce the likelihood of injury. And injury can lead to death in the elderly very easily. A broken hip, can cause all sorts of issues even provoke suicide. Singing is important because it strengthens the diaphragm and other muscles related to breathing. This reduces snoring allowing sleep to be more successful in doing all the repair and other processes, it also should help to prevent Pneumonitis the 10th leading cause of death over 100 years old. And that could rise if we more successfully treat cardiovascular related illnesses, and Alzheimer’s disease and the elderly are less and less likely to have smoked as time goes on. It wasn’t until mid 1954 that we had strong evidence that smoking caused lung cancer and chronic lower respiratory diseases: https://www.cancer.org/latest-news/the-study-that-helped-spur-the-us-stop-smoking-movement.html
    Smoking wasn’t that common until the military started handing out cigarettes in WW1 and WW2. Smoking didn’t really start to come down until about 1964. It takes about 30 years on average for smoking to kill you of cancer, if you are susceptible. Prohibition probably saved many lives. Oddly the depression extended lives as people were “fasting”.

  12. I wouldn’t mind if it were every 5, I’d stick to mid-thirties but without the slow onset of aches and pains.

  13. https://advancedtissue.com/2015/07/the-link-between-staph-infection-and-diabetes/



    Very difficult for our immune systems to kill gingivitis because it has a slimy coating that is nearly impossible to penetrate. This may cause our immune systems to just continue escalating the attack until there is a lot of damage from friendly fire. Similar pathogens have been implicated in Atherosclerotic plaques.

    It is possible our hard working immune systems burn out faster than some time in the past. But then as now, I think other stuff gets us first. I think a lot more of that is pathogen caused and toxin caused than most people suspect. Our immune systems just were not designed to kill some things.

    For that we are going to need cures/immunizations and a cleaner environment. We need to cure all the herpes viruses that infect humans not just chicken pox. Herpes simplex virus 1, herpes simplex virus 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus-6, human herpesvirus-7, and Kaposi’s sarcoma herpes virus.

    And we need to cure all the adenoviruses that can stay in the body. And any other viruses that our immune system can’t completely eradicate.

    We need to end diesel combustion, coal combustion, and remove lead from our cities and farmland.


  14. Lots of things are going downhill as we age the fact that the immune system is as well, certainly does not make it the cause more than any of the others.
    A revved up immune system can often cure cancer…if the immune system does not kill you. Prevention is still unknown. What we do know is that cancer targets people typically not terribly old: https://www.cdc.gov/nchs/data/dvs/LCWK1_2015.pdf
    Only 4.1% of people over 100 that die, die of cancer. That is less than any other age group.
    And it may start decades before death. So many victims got cancer while relatively young.
    Many cases of cancer are caused by viruses. The percentage is not really determined. It is somewhere between 15% and 40%. It is possible a good immune system could have something to say about that.
    We have much stronger immune systems than people born 12,000 years ago. That is because when we were hunter gatherers we did not come in contact with many people and did not need a super powerful immune system. As we began to live in larger crowded towns and cities and were exposed to the diseases of our domesticated animals large numbers died. Those who survived had stronger systems and their descendants replaced those who died. Hundreds of these horrible epidemics happened. Our systems are often too strong now. This is why there are so many autoimmune diseases. https://www.webmd.com/a-to-z-guides/autoimmune-diseases
    Both type 2 Diabetes and Alzheimer’s are looking like they may be autoimmune over reactions.

  15. OK, Mindbraker, that’s a lot of possible remedies… I thought that most of the supplement hype was a just a way of companies to earn money of gullible consumers who rather buy a pill than to exercise.. I know it’s anectdotal, but it’s almost commical when you meet people who take a lot of supplement and look like crap for their age…

    How about some links to back up your claims? Not saying you are wrong, but some quantitative information would be interesting…

  16. Many of the points that you list are indirectly related to the immune system and hence the antiaging treatment mentioned in the article. The immune system prevents cancer (2) to a large extent and who knows how many of the cases of (1), (3), (5), 6), (7), (8), (10), (11), (12) and (19) it is involved in preventing? Asked in another way, is the frequency of occurence of, say, (11) liver disease higher per “life-year” of older people higher than the corresponding frequency of occurence of young people?

    If so, then it may have something to do with the decline of the immune system.

  17. If only a comenter could provide some perspective…. I need instruction of how these factors could be reduced by yoga, stretching and focusing your mind.

  18. Boosting HGH can have a lot of not so positive side effects beyond diabetes risk. https://www.healthline.com/health/hgh-side-effects#side-effects

    If it accelerates cell division that also shortens telomers at an increased rate accelerating that kind of aging. Though you might be able to mitigate that with Cycloastragenol. They want quite a bit for that though.

    You probably also raise IGF-1, increasing the risks of very common killers.

  19. cont. Use reverse osmosis water for drinking and cooking. Take supplements for joints, skin and eye health. We don’t eat whole animals, so there are nutrients we don’t get enough of for skin and joints especially.
    Everyone should take a Lutein Zeaxanthin and Meso-zeaxanthin supplement for their eye health. And lecithin. Lecithin because we have big brains but we don’t eat brains…and least I don’t. And brains need a lot of this stuff. It is found in almost everything, but in small amounts generally. We need more than other animals…because our brains are so big. Salmon oil is also a good idea.

    As you get older your gut may not efficiently absorb some nutrients. A supplement or regular shot may help. B12 is a common one. The American diet may also leave you short on iodine. I take a drop or two a week. If you eat kelp occasionally or eat cod every other day, you don’t need it. I’d suggest the iodized salt route, except that too much salt can be a problem.

    Strength training, and moderate cardio is beneficial. Stretching, relaxation, getting 10-15 minutes of sunlight between 10AM-2PM daily, good sleep, singing (I know that is an odd one and you might harm the people you love), good hygiene, and avoiding contagions, and spoiled food are good ideas.

  20. There are things you can do to address some of the types of aging to various degrees. You can increase the turnover of your mitochondria by doing HIIT (high intensity interval training). The more these are recycled, the better your mitochondrial health. You can reduce your senescent cells by fasting for 4 days in a row every month (or near fasting 500 calories a day virtually none of it protein), and or take fisetin or other senolytics. Telomers at least in the immune system can be extended by Cycloastragenol. You can reduce the accumulation of junk by reducing AGEs in the diet and by assisting their elimination: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704564/
    Various antibiotics, antiparasitics, antivirals may eliminate some pathogens. You can boost NAD+ which provides more power to the cells to do their jobs and self-maintenance. You can reduce your IGF-1 (reducing cancer risk, diabetes risk and other risks) by near fasting every other day or 2 out of 7 days a week. This is different than that other fast thing. This attempts to keep IGF-1 down which requires frequent fasting unless you have a super rare mutation. And you don’t have to eliminate nearly all protein on the near fast days. No alcohol (the studies suggesting low is better are flawed), no tobacco, no lead (even small amounts can cause high blood pressure), filter but don’t ionize air.

  21. Not necessarily. This is one form of aging, we still would likely age by several other mechanisms: Telomere shortening, cross links and other junk accumulation, mitochondria dysfunction, other organelle damage, various proteins being produced in lower quantities impacting all sorts of things, accumulation of injuries, often to the skin, lungs, and DNA, and from pathogens (nearly everyone carries several pathogens which slowly eat away at us. things like chicken pox and toxoplasmosis are never really are completely eliminated by the body).
    If your immune system was what you were destined to die of, and whatever else is 2.5 years down the road, then yes, it would seem to follow. People (at least in the US) are dying of:

    1: Cardiovascular issues: diseases of the heart, cerebrovascular diseases, essential hypertension and hypertensive renal disease 29.8%
    2: Cancer 22%
    3: Chronic lower respiratory diseases 5.7% (80% from smoking, 20% from other air quality issues)
    4: Accidents 5.4%
    5: Alzheimer’s disease 4.1%
    6: Diabetes mellitus 2.9%
    7: Influenza and pneumonia 2.1%
    8: other Kidney diseases (Nephritis, nephrotic syndrome and nephrosis) 1.8%
    9: Suicide 1.6%
    10: Septicemia (serious infection) 1.5%
    11: Liver disease 1.5%
    12: Parkinson’s disease 1.0%
    13: Pneumonitis due to solids and liquids 0.7% (usually because you can’t cough stuff up that went down the wrong pipe because you are too weak)
    19.9% other

    This may help prevent: #7, #10 & #13. Worsen? #5 & #6. +More Arthritis?

  22. Interesting. I can get ibutamoren and DHEA online, and I might be able to persuade my current doctor to prescribe low dose metaformin, since my blood sugar is approaching prediabetic levels. (To be more accurate, prediabetic levels are approaching my blood sugar, it’s not my blood sugar that’s changing…)

    Worth looking into.

  23. I wonder what longterm effect would be if it would tail off then continue to degrade, maintain position a healthy status, or continue to improve.

    Maintaining a healthier immune system with higher cells would greatly increase quality of life.

  24. Unless you can do it again and again. Too simple.

    But wouldn’t it be great is you could . . . and more often than every 2.5 years.

  25. Since none of these are hugely restricted, duplicating this trial shouldn’t be horribly difficult to arrange, given a cooperative doctor.

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