In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’
nature.com
nature.com
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.
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.
There are certainly medical reasons why race is relevant for the results of the study, but the original comment seemed to be dismissing the research as only relevant to a caricatured outgroup. And a justification of "statistics" sounds impartial, but it's from the exact same vein as "_______ people are more likely to default on loans".
In other words white people should still make up the clear majority of every single demographic, lacking any biases. In terms of wealth they should be disproportionately ahead because of the fact that migrants are very rarely rich. So e.g. imagine you had 80% white and then you add enough migrants to bring that down to 70%. The number of rich individuals, as a whole, will probably not change much, meaning it'd be about the same as when whites made up 80% of the population, yet now whites would only make up 70% of the population. So this creates a relative over representation among the wealthy without any sort of bias other than in the socioeconomic composition of migrants.
Where things get really bad though is fertility. In modern times wealth and fertility are sharply inversely correlated. This [1] is a graph of fertility in families ranging from those earning $200k+ per year to those earning < $10k per year. There's a disconcertingly, practically linear, drop in fertility as people earn more money. Those earning less than $10k a year show a 50% higher fertility than those earning $200k+ per year. As a result of this, poverty also multiplies much more quickly than wealth. Due to the nature of fertility (2.x = baseline for sustainability, not 0), this also results in a much larger than 50% effect on relative population sizes. E.g. a group that has 1.5 children on average will gradually approach a population of 0, while a group that has 2.5 children on average will gradually approach a population of infinity.
This creates quite a difficult problem to solve. You can't solve poverty when people becoming wealthy means they stop reproducing in sufficient numbers while, at the same time, those who are at the very bottom of society are pumping out far more children than they could ever independently afford to support. It's like you take one step forward and two steps backwards. And while this is happening you also then start to see increasing social instability and divisions. No idea where all of this will play out but there's no doubt we live in one of the most interesting times in our species long existence.
[1] - https://www.statista.com/statistics/241530/birth-rate-by-fam...
> The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age.
Who knows if this set of treatments will work for other demographics? I'd certainly bet it'd work differently for women, given the differences in hormonal balances. (And IIRC there are different recommended steroids for women - since at least one of the drugs in this cocktail was a steroid, I'd think that would come into play)
Why attach race, age, gender, and class to the idea that lifestyle changes are hard? I'm pretty sure everyone finds them hard.
That sounds to me like a big deal, given that most people find fasting difficult (and unpleasant).
Cellular metabolic reprogramming controls sugar appetite
I enjoy the benefit.
The actual act of doing these things are antithetical of fun for me.
I do them because they work. If I lose motivation in life, it's the first thing I stop and the hardest to start up again (been many years that I've worked on self improvement)
Good on you that it feels that way to you. No, I will never feel that way. People are different.
At this point, most days it’s not even hard. When I’m hungry I just realize that the hunger is temporary, and it’s honestly unrelated to the degree to which I need food. And tbh nowadays I can tell when my body actually feels weak and needs food, and when it’s just whining.
I think of it like getting sleepy. Just because I feel sleepy doesn’t mean I should just take a nap right there and then.
You call that a fast? As someone who's lost and kept off about half their body weight, I feel qualified to tell you that skipping a meal here and there is not fasting. In fact, if you're eating every day you're not fasting. Fuck, I mean, I only eat about 1.5 meals a day as a requirement of merely maintaining my current weight (and even that doesn't always work).
"Intermittent fasting means different things to different people, even among the research community. This lack of specificity has been a source of consternation for experts in the field of fasting, with some advocating that the phrase be retired. Often, when someone uses this phrase they may actually mean one of the following:
Time-restricted eating Alternate-day fasting Periodic or prolonged fasting (multi-day) - less frequently referred to as intermittent"
I guess since I never let myself go as much as you did, I'm not allowed to share my experiences?
Fasting increases vasointestinal peptide VIP which boost growth hormone.
Yes, you feel hungry. But, once you're there you are also laser focused (at least I am). My morning productivity and ability to sink into problems lasts all day, instead.
I haven't got the other part, the ketogenic diet, yet.
Then I develop this habit of waking up early. Initially I wasn't very comfortable but now I too can say it is more enjoyable.
I guess you get the point.
For years, I slept as late as possible, and hated waking up early. Something changed this summer, wherein I suddenly began waking up super early of my own accord, and then going to bed early to compensate. And I enjoy waking up early now.
I'm still unsure if this will be the new normal, or if it's a phase that will go away as suddenly as it began...
Right now I do a 24 hour fast (dinner to dinner) about once a week.
Fasting for 24-36 hours for me isn't bad. But days 2 to 3 when I do a 3 day fast I find it extremely difficult to concentrate/focus on anything difficult. By day 3 my energy is usually shot as well and I just don't want to do anything but watch tv.
If anyone has advice beyond sugar I'd love to hear it.
Obviously saying 'could' is not the same as saying 'should' and it's not very safe to do drastic changes to your diet without consulting a MD.
Generally after not eating for a long time I’ll be pretty hungry, but a lot of times things won’t seem appetizing. And when I do eat I usually fill up quick. And have to wait a bit to eat anymore.
Stories like this are part of what convinced me to give fasting a go. And after going on 2 years of it now, I've had the exact opposite experience of that which you describe. In particular I don't eat the same total amount of food/calories, I eat substantially less. And somehow I have substantially more energy. The reason I decided to try out fasting is because it seems evident that we're eating far more than we need, as the absurd rates of obesity/overweight attest to.
Blaming the lack of exercise is somewhat nonsensical as can be shown from more ancient peoples. But it can also be shown numerically. I now bike around 5k a day and that burns about 100 calories. That's 15 minutes of biking to burn the equivalent of about a third of a slice of pizza. Exercise is of course important, but not for the calorie burning. If you eat poorly (or too much) it doesn't matter if you spend hours at the gym - you're gonna get fat.
I think the actual truth is that in modern times we've trained our bodies to expect far too much food. Fortunately this is really easy to reverse. It just requires accepting a discomfort that fades somewhat quickly over the months.
That must be the worlds smallest slice of pizza. 100 calories is nothing, about 1 apple's worth.
Cleansing, or detoxing, yes. Fasting, no. The people around you are simply misusing the term.
Fasting meaning abstinence from food is fairly well-established. Breakfast is literally break-fast, with the fasting period being overnight while you slept.
They also find hospitalization "difficult" but that doesn't stop them from OD'ing on sugar and junk food. It's not a matter of difficulty. It's a matter of priority. We (in the USA) live in a culture that devalues the personal responsibility to personal health.
Would you not at least try to live a bit longer for only $25/year and a once a day pill?
I bought a 6 month supply of 850mg Metformin when I went to Mexico because I intended to take it long term for anti-aging benefits, and although the GI issues were almost non existent, my energy levels after waking up plummeted. I felt physically tired after waking up, and the only thing I wanted was to go back to bed.
I then tried 425mg and had the same problem. I wonder if it's a symptom of low blood sugar? I didn't feel much hunger in the morning. It was a weird experience and I'm a bit sad I had to discontinue it.
I'd love to take it but I tried berberine, which is supposedly similar in effect, and got major low blood sugar.
The only issues with Metformin are occasional digestive issues(diarrhea) and the slight chance of lactic acidosis.
[1] https://www.mayoclinic.org/drugs-supplements-dhea/art-203641...
Never heard of that crowd. What is it that they do? Try experimental treatments on themselves?
(I'm not an "antiaging enthusiast" other than eating healthy and regular exercise but I have done some reading on the subject)
If you want to read for example about sauna I recommend thishttps://www.foundmyfitness.com/topics/sauna she also has a lot of stuff about other things I mentioned
Why is it lousy to do formal research on "stacks" people have been using for years?
I managed to buy some online. I think it was from a UK site, but I can't remember. Makes me spotty though, so i don't use it to often.
Just because you don't happen to know the answer doesn't mean the answer is complicated.
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?
> 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.
The best strategy for me is lower metabolism, undereat, and reduce cellular damage and senescence. In some cases, senescence can be reversed (a friend of mine is doing a beta cell research at UCLA, and they've done that to some extent.) Of course, there are other strategies, involving stem cells, but I'm not familiar with that part - maybe they can compensate the negative effects of autophagy.
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.
"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 :)
Relatedly, we are still evolving, and social policy is part of what dictates this.
> Getting old and dying is required for evolution to transpire.
I don't think this is actually the case - only dying is required, not the getting old part. If a lion is still having no trouble catching zebras at 20, why shouldn't he stick around having kids? (The answer is probably something along the lines of "keeping this gene carrier at maximum health is significantly harder than spreading through fresh, if diluted, gene carriers" - though some species do seem to manage agelessness, most intriguingly the naked mole rat)
Though far more removed from us or many other things, some Jelly Fish take this even further by reverting to earlier stages of life. https://en.wikipedia.org/wiki/Turritopsis_dohrnii
Take Jelly Fish, they are biologically immortal, been around 500 million years, not to bad. They were the first animals to evolve nervous systems, not sure the timeline of the biological immortality evolution, but they must have continued evolving because there are different species (some have evolved eyes and others not) and I believe all species are biologically immortal.
Only via predators. The immortal Jellyfish not only don't die from aging, they don't generally die of disease, starvation, temperature changes or any other stresses...in fact it is those stresses that trigger their reversion from sexual maturity to biologically rewind to a polyp colony where they begin the start of their life cycle all over.
I tend to agree statistically speaking it seems highly unlikely, but its such a bizarre thought experiment, I can wind up concluding it is statistically highly unlikely there isn't Jellyfish in the wild that are older than the dinosaurs. Unfortunately, we can't age these Jellyfish.
Unfortunately we can't age these Jelly fish or even confirm they have undergone the reversion transformation process (except under lab observation).
So while I am not saying yes, a single jelly fish has lived the entire 500 million years, its certainly possible and the idea behind biological immortality. Maybe one day we can figure out a way to age them and find some older than the dinosaurs.
Genes most definitely do not want to promote evolution in any sense. Since evolution by definition implies the replacement of currently existing genes with new genes.
That is, if a gene's options are "copy into clone" or "copy into 100% optimal genetic superman, with the only common gene being me, left completely untouched", I assume any given gene would "choose" the latter.
Which is to say, presuming a given gene is already helpful and is "core" to the organism's functionality, that gene would see evolution as a helpful service that causes it to end up copied into better-performing descendants, rather than same-performing descendants.
This also serves as a decent explanation of why sexual reproduction persists even in species that can also parthenogenetically reproduce: the "good" genes are betting on being retained, and getting the "bad" genes culled out in the process.
For example apoptosis happens all the time in human cells. If a cell believes it's infected by a virus or a cancerous mutation, it will voluntarily destroy itself. That's because its continued existence threatens its genetically identical cellular neighbors. Thus genetic inclusive fitness is maximized.
But what absolutely wouldn't happen is such self-sacrifice on a species wide level. Two random members of a species are not closely enough related for self-sacrifice to maximize inclusive genetic fitness. Almost certainly a non-complying free rider mutation would arise in one or more individuals, and exploit the other species' members altruism.
The hypothesis was that aging evolved as an adaptation to accelerate the evolution of the species. To see the absurdity of this hypothesis, consider that if this logic held, then mate guarding would definitely not exist. In fact just the opposite, males would routinely solicit the highest-quality males they could find to mate with their females. And be happy about it. After all this would also accelerate species wide evolution, at the expense of individual fitness.
Which means that, if there's a trade-off that involves killing the current host of the gene, in exchange for creating a new host (a descendant) that has the same gene, but is otherwise more inclusively-fit because it has better other genes—then any given gene will "want" to take that trade. Thus the evolution of reproductive strategies that require the deaths of one or both parents.
Mate-guarding (and, really, sexual reproduction preference generally) can be understood as a desire of your more-fit genes, to kick out your less-fit genes and replace them (in your descendants) with more-fit immigrant genes, to build a more-inclusively-fit descendant where the gene has higher likelihood of continuing the next step of exponential-spread-to-fixation.
It sounds too simple to be true, but it's an interesting information theoretical based hypothesis.
It's just that after you reproduce and get your offspring on their own feet, continuing to live is optional (for evolution), so no optimizations evolved to continue life far beyond that.
Evolution isn't trying to kill you, it just doesn't care about helping you beyond reproductive age.
So once you get to like 10 kids, you're really not getting much more evolutionary advantage for each additional kid. You don't have the same relentless pressure that privileges genes that are provide extreme longevity.
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-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!
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.
Discussing “why” this outcome occurred is ridiculous. Look at the numbers.
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.
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
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!
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.
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.
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."
Fahy, G. M. et al. Aging Cell https://doi.org/10.1111/acel.13028 (2019).
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." ;-)
It's interesting to me how important the results are and how underreported this research is at the same time.
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.
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)
That's a significant disclaimer. I wish they'd not even call such things a trial.
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.
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!