16 ms·
In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’
- tobr 7y ago9 people, no control group.
- ralusek 7y agoBiomimicry. Start with what we know works: the 9 lives of a cat.
- asdfman123 7y agoPlus if they accidentally kill someone they still have 8 lives left.
- MartianSquirrel 7y agoThe results were a surprise even to the trial organizers — but researchers caution that the findings are preliminary because the trial was small and did not include a control arm.
- jjoonathan 7y ago"Enough for Nature! Next time, let's see if we can get away with 8!"
- red75prime 7y agoI would say that even one person experiment with documented deep reversal of age-related changes deserves publication and further research.
- jjoonathan 7y agoThe fact that it deserves further research is precisely why we shouldn't frontload the prestige incentives. That's how you get clickbait. We don't want clickbait, we want further research, but if we incentivize based on clickbait, clickbait is all we're going to get. Let's not.
- Pfhreak 7y ago9 men, no less.
- averros 7y agoWhen you do an exploratory experiment you want to have your group to be as homogeneous as possible. That's why there are lines of lab mice which are nearly clones of each other. Never ascribe to racism that which can be adequately explained by your own ignorance.
- scottlocklin 7y ago1) DHEA is not a diabetes med. In fact it's a steroid (not really an anabolic one, though it is a precursor to anabolics) and illegal in the EU. It is a substance which is lowered in older people, so older people supplement with it. 2) Metformin is a diabetes med, and it's used by antiaging enthusiasts independently and along with growth hormone 3) Fasting creates larger growth hormone spikes, and improves sugar clearance. Dunno what it does to DHEA; eat lots of eggs for that one. So, this (lousy, but interesting) study is basically "fasting by using drugs." Meat heads and antiaging people have done stacks like this for years. Unclear whether or not it actually helps with longevity, but it probably improves quality of life. So does fasting, and it don't cost as much.
- DuskStar 7y ago> So does fasting, and it don't cost as much. If a "rich old white dude" could get the health benefits of fasting for a bit of cash, a lot of them are going to pay it. Lifestyle changes are hard, while cash is 'easy' for a significant part of what I imagine to be the target market. EDIT: Apparently I should clarify the "old white dude" part of this. The study in question consisted entirely of "9 white men between 51 and 65 years of age", and I consider it entirely possible that this particular cocktail only works for that demographic.
- tyri_kai_psomi 7y agoor simply put: time is the real currency here, money isn't. Lifestyle changes require a significant time investment.
- zarkov99 7y agowhy white and dude? aren't there other kinds of rich people? and wouldn't they also pay?
- shrimp_emoji 7y agoStatistics
- magna7 7y agoI'd wager that it's the metformin. Metformin inhibits pathways associated with mTOR (the growth signaling protein). When you inhibit this pathway, it tells the body to start the process of autophagy. It's the same process that occurs during fasting, and it's the same reason that the mTOR inhibitor Rapamycin has been shown to extend lifespan in mice and dogs. This is also why fasting has been shown to increase lifespan. It seems like if you don't constantly tax your body with food (growth signaling), then you can allow the body to repair itself. If you don't give it a break through fasting, then your growth hormones will be continually signaling to activate mTOR within your cells and thus never start the process of autophagy (cell death, and regrowth).
- jostmey 7y agoBiology is not that simple. There's not going to be a single magic compound. Slowing the aging process is massively complex and will probably require a cocktail of treatments
- darkerside 7y agoWhy do you say that? Biology is usually very simple. Eat food, live. Don't eat food, die. Drink water, live. Don't drink water, die. Just because you don't happen to know the answer doesn't mean the answer is complicated.
- powersnail 7y agoJust because you can say something in four words, doesn’t mean it is simple. You eat, you live. Sure. But why? What happens to the things you eat? What can you eat? What/how/why is the pain in your stomachs?
- darkerside 7y agoUgh, please take it in context. That was in response to something. > There's not going to be a single magic compound. Slowing the aging process is massively complex and will probably require a cocktail of treatments My counterpoint is, slowing aging could easily be the result of a very simple compound. It's irrational to assume it must be complex just because we don't know it.
- rwj 7y agoThe sample size is so small, that the results are nearly meaningless.
- jlarocco 7y agoComments like this aren't helpful. Literally nobody is claiming the results are solid evidence for anything other than that one small study had an interesting and unexpected result. And the results aren't "nearly meaningless" - they're an indicator that maybe a larger study should be done. I doubt anybody gets funded for big studies shooting into the dark, so smaller "what if..." studies like this are valuable.
- ALittleLight 7y agoIf 9 people took a substance and died that would be a compelling enough sample size for me not to take thing. Likewise, 9 people reporting a positive result seems meaningful enough to encourage further study (provided effect size is large enough)..
- nikolay 7y agoWith the placebo being so strong, sample size of 9 is too small for any conclusion.
- James_Henry 7y agoDo you know how strong the placebo works on Horvath's epigenetic clock? I don't think that research has been done, but it will be soon I am sure and it will be incredibly interesting to find out. Even without knowing that though, I'm surprised, and so is Horvath himself, that they found a full-on reversal of the clock. I don't think anyone was expecting that. I'm betting we won't see that kind of reversal in a future placebo group, though if we do I'm going to be getting myself some good placebo!
- nikolay 7y agoThe placebo itself is magical enough so it could be extended to pretty much anything and that's why quality studies are done certain way. If can understand the placebo, then and only then we can then explain what it could do and it can't do.
- flyGuyOnTheSly 7y agoIt just dawned on me that getting old and dying is most likely an evolutionary chicken and egg problem. If you didn't get old and die, evolution of your species would grind to a halt. Getting old and dying is required for evolution to transpire. I can't see any reason why it must be an absolute truth.
- jhedwards 7y agoI would imagine there's a fundamental limitation in DNAs ability to be copied over and over without information loss.
- SolarNet 7y agoSure, but we can correct for that, we have the ability to reliably store copies of the information in DNA (a person's full genome is only a few gigabytes) with error correction (or at least verification).
- thfuran 7y agoOur cells are mostly diploid. But some organisms have many more copies of each chromosome - strawberries have eight. With that kind of redundancy, it should be vanishingly unlikely for a random error in DNA replication to make it into a majority of copies and any systematic error severe enough to cause it probably messes up the cell enough for it to be culled by other mechanisms.
- aflag 7y agoHasn't it been doing so for billions of years now?
- jjoonathan 7y agoOnly with strong selective pressure killing off the bad mutations (with is many/most of them). "But most human babies don't die. There are a bunch of mutations per generation, but not an exponentially compounded bunch of infant deaths, so how does our population get rid of bad mutations?" Because sperm are unit tests. The overwhelming majority of them die. You've got to regularly run the unit tests if you want to keep the codebase healthy :)
- DuskStar 7y agoSome people seem to think that there'll be a single cure for aging - a miracle drug, health regimen, or whatever flavor of the week happens to be in the news at the time. I think that if we get a cure for aging in our lifetimes it'll be things like this - killing aging with a thousand tiny cuts. Assuming that this replicates and actually increases either lifespan or healthy lifespan, of course. (I'd rather have a 50s body until I'm 75 than continue aging past that point, even if I'm still dying at 76)
- magna7 7y agoCentenarians have been shown to have increased healthspans. They still get the same diseases as everyone else, however they get them much later in life (90s, 100s). That's all I'd want. If we can get medical science to a point where healthily living to 100 is common, then that's a win for everyone and it'll save us a ton of money. The problem is, like you said, that it's unlikely to be some miracle drug; it's going to be small routines and habits throughout your life that will require willpower and discipline, so that'll exclude a lot of people unless we restructure society in a fundamentally different way.
- theothermkn 7y agoAubrey de Grey has said numerous times that he suspects that if we were able to repair mithochondrial DNA, that has about a 10% chance of being all or most of the anti-aging puzzle, in his estimation. IIRC, he admits this is speculation. Still, he's no slouch in this layperson's book, so his statement gives me the warm fuzzies.
- bigend 7y agoEvery time I read about something related to slowing or stopping aging, I think what the world would be like with Trumps and Putins that would live forever.. hrrr..
- klipklop 7y agoHow do you know they are already not on experimental anti-aging therapy? A scary thought.
- chrisco255 7y agoWell, in the U.S. we have presidential term limits. We probably could use them in Congress, too, though.
- Amygaz 7y agoI have no ef-inf clue why it was a total surprise. Metformim, is already known to affect in multiple ways the epigenetics, and the immune system. Also the so-called epigenetic clock is based on the observation that as we age we are more methylated. Reversing this has not been shown to be true, but it was shown to improve certain functions, like our production of T cells. This such a click-bait piss-poor paper I can’t believe it’s in Cell. There’s absolutely nothing new, and no proof of anything telling me they have reverse of stopped aging, or even a fraction of it.
- busyant 7y ago> This such a click-bait piss-poor paper I can’t believe it’s in Cell. There's a lot of politics in what gets published in prestigious journals like Cell (also, this paper was published in Aging Cell, so not quite as prestigious). Amusing anecdote: In grad school, one of the profs in my department submitted a manuscript to Cell (this was back in the 1990s). His lab had done an amazing genetic study. There was a more famous lab at another University (run by a future Nobel prize winner) that had performed a complementary research study using an in vitro system. Both labs submitted their papers to Cell "back to back." Ben Lewin rejected the genetics manuscript (one reviewer said the genetics research belonged in a more 'archival' journal). Lewin accepted the manuscript describing the in vitro work of the more famous lab. A few months later, the anonymous reviewer was visiting our department (to give a talk) and he revealed himself as the reviewer to the professor who had submitted the manuscript. Professor asks, "I was honestly shocked by the review. <famous lab's manuscript> was just dotting the Is and crossing the Ts of our research." Reviewer responded with, "I thought [rejecting your manuscript was] what Ben wanted me to do." Probably did not help that the reviewer had been a post-doc in the famous prof's lab. That's just one story that I am pretty familiar with. I have heard many others (e.g., famous prof telling editors stuff like "<shitty> paper gets accepted or we will submit our next groundbreaking paper elsewhere."
- sebringj 7y agoI would point toward someone like David Sinclair at Harvard Med and his team's more rigorous approach and more measured progress rather than some study of 9 people. Nothing to see here.
- malicioususer11 7y agoA completely readable artcle from Nature? Nice. :)
- chiefalchemist 7y ago>“But the results are not rock solid because the study is very small and not well controlled.” That's a significant disclaimer. I wish they'd not even call such things a trial.
- LeonB 7y agoIt’s not worth reporting at all on such a small uncontrolled trial. There is no value in this other than providing funding for a larger trial. Discussing “why” this outcome occurred is ridiculous. Look at the numbers.
- nabla9 7y ago>It’s not worth reporting at all on such a small uncontrolled trial. You can't categorically say so. Even sample size of one can be significant if the effect size is large enough or the outcome is surprising (like reversal instead of slowdown). Online forums suffer from "sample size meme" and "correlation is not causation" meme. People just drop them into discussion as a counterargument because that's all they know. Both of them can be proper counterarguments after you consider the context and other factors.
- nikkwong 7y agoCan someone enlighten me as to why a study such as this one may be undertaken without a control group? I mean, what's the point? If the study ends up landing on some exciting conclusions, not having a control group creates more questions than answers. Is there a budgetary constraint at play here or are researchers sticking their feelers out in all kinds of directions simultaneously trying to figure out which direction may be the most promising?
- driverdan 7y agoBecause the larger the group the more expensive it is to run. This is a very early experiment to see if there's anything worth doing a larger study on.
- James_Henry 7y agoYes, this is very standard practice. You can still learn a lot with a small sample size and no control, especially when you don't know much. It's a big deal that they are able to see a full on reversal of Horvath's clock whether or not it was in a handful of people or a thousand!
- ThinkBeforeDo 7y agoWhere's a link to the actual paper/ peer-reviewed publication?
- qnsi 7y agoShould be here but can't get it on sci-hub Fahy, G. M. et al. Aging Cell https://doi.org/10.1111/acel.13028 https://doi.org/10.1111/acel.13028 (2019).
- Tringi 7y agoI'm searching for it too, and I can't find the actual text. Somebody doesn't want us to begin mixing that cocktail ourselves :D
- qnsi 7y agoI don't think it's published yet. Should in the recent tab on this site I think https://onlinelibrary.wiley.com/journal/14749726 https://onlinelibrary.wiley.com/journal/14749726
- Camisade 7y agoWhen I first saw that article, I swear it contained a link to the associated paper in Aging Cell. Now when I go to the Nature.com article, that link is no longer there. How many people are currently thinking, "All three drugs/compounds are pretty well understood, and reasonably benign when administered under a Doctor's supervision with periodic blood testing; in the absence of specificity, let's just start with fairly standard daily prescription doses and see what happens..." As someone afflicted by 'chronic aging' (at the rate of one year, per year), I'm hugely fascinated by prospective "cures." ;-)
- phaedrus11 7y agohttps://www.gwern.net/docs/longevity/2019-fahy.pdf https://www.gwern.net/docs/longevity/2019-fahy.pdf
- gwern 7y ago
- kgin 7y agoEverybody's a critic about study design, geez. Studies cost a ton of money. If you can get an interesting signal in a small study, that can be a good reason to invest more money. If you get s strong signal for a surprising result, it's worth talking about and can get into serious journals.
- aaron695 7y agoIs Metformin Really a Wonder Drug? http://freshlook.annals.org/2019/08/is-metformin-really-wonder-drug.html http://freshlook.annals.org/2019/08/is-metformin-really-wond...
- dingdingdang 7y agoWhat is the "third" drug in this combo, the article says: ".. growth hormone and two diabetes medications". So far only the DHEA and Metformin has been discussed and I have no access to the source article.. any takes? edit-1: the answer is that the nature.com article got it wrong and other net sources parroted that article, https://www.leafscience.org/study-results-suggest-human-aging-can-be-reversed/ https://www.leafscience.org/study-results-suggest-human-agin... is more accurate overview: there is no third drug involved. edit-2: scratch edit-1, HGH was obviously the primary growth hormone given and for some reason DHEA was counted as an anti-diabetic rather than a hormone (it is both) together with Metformin. Now I would just like to know the dosages involved!
- greatpatton 7y agoIt is in the paper: of the trial, rhGH alone (0.015 mg/kg) was administered to obtain an initial insulin response, and during the second week, rhGH was combined with 50 mg DHEA to evaluate insulin suppression by DHEA alone. During the third week, the same doses of rhGH and DHEA were combined with 500 mg metformin. Beginning at the fourth week, all doses were individualized based on each volunteer's particular responses.
- bennylam 7y agoThough it happened some times ago, the TRIM clinical trial was really a real small scale research. According to the following info: http://interveneimmune.com/?ignition_product=the-triim-trial http://interveneimmune.com/?ignition_product=the-triim-trial http://interveneimmune.com/?page_id=1200 http://interveneimmune.com/?page_id=1200 This company is found by Greg Fahy, PhD, Chief Scientific Officer, Co-founder -Published the first report of thymus regeneration in a normal human; Granted patents on methods for and applications of human thymus regeneration –Fellow of the American Aging Association (since 2005), Former Director of the American Aging Association (16 years) –Editor-in-Chief, The Future of Aging: Pathways to Human Life Extension –Awarded the Society for Cryobiology’s Luyet Medal in 2016 –In 2009, showed indefinite survival of rabbit kidney transplanted after cooling to -130° Celsius; Led 21CM team as co-winner of Small Mammal Brain Preservation Prize, 2018 winner of Large Mammal Brain Preservation Prize and Steve Horvath, PhD, Scientific Collaborator -Professor of Human Genetics & Biostatistics at UCLA -Developer of the DNA methylation clock of human aging, as well as author of seminal papers demonstrating ability to accurately predict life expectancy, onset of Alzheimer's, cognitive decline, and more -Paul G. Allen Distinguished Investigator -Ph.D. Mathematics at UNC, Sc.D. Biostatistics from Harvard University
- gwern 7y agoFulltext: https://www.gwern.net/docs/longevity/2019-fahy.pdf https://www.gwern.net/docs/longevity/2019-fahy.pdf
- kunkelast 7y agoI think I can make a study/research of this size on my own, among a small group of friends :)
- amai 7y ago„The atrophy [of the thymus] is due to the increased circulating level of sex hormones, and chemical or physical castration of an adult results in the thymus increasing in size and activity.“ ( https://en.wikipedia.org/wiki/Thymus https://en.wikipedia.org/wiki/Thymus ) So the study might simply have show, that by decreasing sex hormones the thymus is stimulated to grow. But the side effects of no sex hormones might be much greater than the advantages of a younger immune system.