2.5 Years of Aging Reversal from Metformin and DHEA

A small study showed 2.5 years of aging reversal. The people were 1.5 years younger according to epigenetic markers than when they were first measured one year prior. The trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, in the treatment cocktail. [Aging Cell – Reversal of epigenetic aging and immunosenescent trends in humans. Study by Horvath of UCLA.]

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age‐related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (−2.5‐year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention.

Nextbigfuture covered this work a few days ago. Here we summarize some other antiaging and age reversal work. This is other work being done by other companies.

1. AgeX is working on small molecules and cell lines to package exosomes with mRNA and telomerase to change cells in the body to restore full regeneration and enable antiaging.

2. Juvenescence is creating antiaging therapies using artificial intelligence and biotechnology with a near term goal of extending human lifespan to 150 years. They just raised $100 million in a Series B round, including a total of $10 million from its founders and a further $10 million each from four cornerstone investors, including Grok Ventures, the investment company of Mike Cannon-Brookes (Atlassian cofounder), and Michael Spencer’s private investment company, IPGL. This brings the total to $165 Million that Juvenescence has raised in 18 months and speaks to the extraordinary opportunity as well as interest in developing therapeutics with the capacity to modify aging.

They have 12 programs based on hard, rigorous science, to attempt to modify aging. They range from stem cell research to senolytics (removing zombie cells) to modifying or preventing Alzheimer’s and Parkinson’s diseases.

The Juvenescence teams believes within five to seven years at least four anti-aging products will be on the market from their portfolio of about one dozen antiaging companies.

3. Harvard Genetics Giant Geroge Church and Noah Davidsohn, a former postdoc in his lab, have engaged in a secretive antiaging venture called Rejuvenate Bio. They are making old dogs new by reversing aging using a combination of over 40 gene therapy changes. They have conducted gene therapy on beagles and are currently advertising for Cavalier King Charles spaniels to use gene therapy to fix their hearts.

They have identified many other targets for gene-based interventions, studying a database of aging-related genes.

Most of the work was done in mice, where they have extended the life of mice by a factor of two. Nextbigfuture notes that this would mean mice would live 6 years with treatment instead of 3 years.

SOURCES- Juvenescence, UCLA, Aging Cell, Nature, Rejuvenate Bio, AgeX
Written By Brian Wang, Nextbigfuture.com

25 thoughts on “2.5 Years of Aging Reversal from Metformin and DHEA”

  1. Anti-aging  is a dread for every woman as they age. I was literally afraid that I would end up suffering with such loose skin but the homemade face masks for skin tightening definitely did its magic. All of these masks that I have tried have been made with ingredients that are lying around in your house. If you are done using the synthetic products, I would suggest going organic!
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  2. I’m not saying cancer will be easy. I’m saying that given the requirements of the two tasks, cancer will probably be solved as soon or sooner than eternal youth.

    “Sooner than eternal youth” is not the same as “easy”

    And best of luck on Monday. I’ll pray for you.

  3. Given that I currently have cancer and am starting chemo on monday I will hope you are right, however I think you underestimate the difficulty.

  4. Tesamorelin has been used for several years by some fancy anti-aging clinics
    Clinical trials of such substances, called hGH secretagogues, are ongoing, and Dr. Coles says he expects the FDA to approve at least one of them, an oral spray called tesamorelin, by the end of the year. The primary indication would be for patients with HIV, but Dr. Coles suspects physicians will leap to use it for anti-aging even if it is not officially approved for that purpose.

  5. The justification was as you described, but restoring your biology to what it was when you were younger is what “making people younger” means.

  6. The idea behind this study is not to make people younger, but to expand the pool of naive CD4+ T cells, thus restoring the diversity of T receptors repertoire. Elderly individuals having a diverse repertoire of T cells respond better to vaccines (eg seasonal flu), which is very Important for survival at an advanced age. Naive T cells are generated through the thymus, which is present and active mainly before puberty, and almost completly absent by age 40.

  7. You keep using this image for rejuvenation/anti-ageing articles which shows the progression of ageing, not its reversal. Pay someone on Fiverr to swap the youngest and oldest faces around.

  8. Actually, in addition to the epigenetic markers, they did see some signs of thymic regeneration, and a restoration of immune cells to a more youthful ratio. So it wasn’t all markers.

    This was a fairly cheap and small study, the results were certainly promising enough to do it again with better funding and a larger group.

  9. Well, it was mentioned in the previous NBF article. As well as being mentioned in the actual paper reporting on the trial. (Which you can reach by following the links.)

    Which is quite interesting. I was looking for the actual treatment protocol, and it seems that they brought the drugs in in stages, and individually adjusted the doses of each component to get the HGH response they were aiming for without any increase in insulin resistance or blood sugar. So, not as simple as “take these three things.”

    Here’s that link again, the paper is good reading: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028

  10. OK. I was just stuck there. How did Asteroza know there were 3 components?

    control-F “3” nothing

    control-F “three” nothing

    Am I missing on part of the story?

  11. A couple of people have brought up how biomarkers aren’t quite the same thing as actual health outcomes in a clinical trial. If anyone wants to learn more about this subject, they should google “surrogate endpoint”.

  12. Somehow I was thinking the hormone mentioned covered both rhGH and DHEA in my mind. The initial PR elsewhere just mentioned they had 3 things.

  13. No. That’s not true.

    A study being “stopped for efficacy” is a real thing that is reported in the literature. Where the new treatment is so obviously an improvement on the old one that continuing to give the control groups the old treatment is considered unethical.


    It’s not that common, but that’s because most medical trials aren’t such obvious improvements.

    In such a case the result is that all the trial participants get the new treatment, not that everyone goes home to die. In the rain.

    To answer Brett’s question: This isn’t a case of the treatment clearly and obviously producing better health. This is a case of the new treatment producing a significant improvement in an indirect biochemical marker. They HOPE that the marker has a strong correlation to actual health, but there is a long history of that not being a slam dunk.

  14. From the first link

    we combined rhGH (recombinant human growth hormone) with both dehydroepiandrosterone (DHEA) and metformin

    Though I fail to see how you knew they had 3 components without reading that.

  15. An earlier version of this used just growth hormone and dhea. Metformin was probably added because growth hormone often has negative effects on insulin sensitivity.

    There is evidence metformin helps with insulin because of its anti-aging benefits.

  16. …ethics of terminating the protocol…

    That is never a consideration in medical studies. After the end of a study and If the subjects want the continued benefits they must pay like everyone else or do without.

  17. some epygenetic markers might be good to measure the aging on general but just because they got somewhat reversed doesn’t mean much. After all, they are indirect measures of something that is hard to define precisely…

  18. It remains to be seen which would be easier. Curing all forms of cancer or reversing/stopping aging. Aging immune system and cell lines contribute to cancer risk, so even without any progress on the cancer per se we could have greatly reduced cancer rates from rejuvenated immune systems…

  19. The first article tried to tie thymic regeneration to anti aging. Which, itself, makes no sense. And their rationale abou CD38 accumulation being the lynch pin is just as baffling.

  20. Accidents, murder, suicide, robot cars facing trolley problems, and of course rogue household cleaning robots, sure.

    But cancer? Arguably not.

    Cancer is a problem with uncontrolled cell growth. If we have enough control over cell growth and replacement to reverse ageing then cancer is most likely to also be cured.

    It’s kind of like the development of cars and the massive road networks needed to support them. The very same tech that enables mass production of cars also allows the earth moving and construction equipment needed to make the roads.

  21. ” The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month.”

    This is starting to get into the range where the ethics of terminating the protocol become questionable. I wonder what things would have looked like after another year?

  22. If we manage to reverse aging things will get nuts. Course cancer, accidents, etc will still kill us off, but even so-things will get incredibly complicated and awesome.

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