The 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.
The 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.
When 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.
1) 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.
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.
But the obvious doesn't need to be continually restated. Rather, it is usually stated in furtherance of some motive - contrast someone expressing frustration at the police saying "everyone in that town is white", with a loan officer saying "everyone in that town is white".
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".
Hey guys, just wanted to let you know how happy I am to have had the chance to read this riveting discussion on my favorite science forum. I learned so much.
And 63% of all people in the country are white. In 2000 that was 69%, in 1980 it was 80%.
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.
> 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)
Well, "old white dude" comes from the study participants. "rich" comes from people you want to sell to and/or people who have the resources to pay you.
Fasting is easy and fun, you just have to work up to it. You can just go from zero to not eating for a week. Building up your tolerance to it takes a bit, like anything else, but when you do it improves mental acuity, gets you a general sense of well-being and energy too.
The idea of fasting and the reality of fasting are different. The idea is more painful than a committed effort. Once you accept and embrace the fast, it’s freeing. Like running every day.... once you know you’re going to do it, the resistance withers.
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.
As someone who's gone multiple days in a row without eating non-voluntarily, you're never going to convince me that fasting for extended periods is fun.
I've done both alternate day fasting and longer fasts (voluntarily) and I'm also in the same boat. It's not fun. If it didn't provide a health value to me, I wouldn't do it.
After doing intermittant fasting for half a year I think you shouldn't generalize too much from your own experience. Yes, it gets easier but it stays painful and requires a lot of willpower ime.
I’ve been doing it for about a year and a half, just skipping breakfast each day and lunch one or two workdays a week.
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.
> I’ve been doing it for about a year and a half, just skipping breakfast each day and lunch one or two workdays a week.
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).
this is just different definition of what fasting is. What he's doing is time-restricted eating but it is a form of fasting. You are just doing longer fasts. No need to gatekeep
"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 IF but I can workout before my 11 to 5 eat window. It eliminates hunger. I time it when I am done exercising i drink a 64 ounce smoothie that i concoct with targeted nutrients.
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.
There was a time I wouldn't wake up early. I enjoyed sleeping till late morning. At that time I was kind of unable to feel why people who wake up early insist that it is more enjoyable than sleeping till 9 AM.
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.
Damn, I had to do a double take on this. 9 AM is super early for me, noon is normal and 2-3 PM is sleeping late. What is appealing and tolerable will not be the same for everyone and sometimes it's not just a matter of getting used to something. It's hard to say in advance.
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...
Uh, do you mean two weeks of only water? Do you do this for weight loss? Do you work out? I would be very afraid to mess-up my metabosm. How do you prevent that?
Long term or repeated fasting should actually decrease your body's metabolism rate; which is a good thing if you want to age slower. (I.e. think about species who have slow metabolisms, turtles, for one, who live very long lives). I do alternate day fasting (48 hour fasts, every other day) and realized I now need far fewer calories to get by than I used to. Obviously anecdotal but I feel great!
It’s just another challenge in life like all the other ones. Once you’ve started dipping your toes in you slowly realize the state of homeostasis starts to feel a bit perverse. Obviously it feels good to be fed, but, like in other areas of life, if we never chose to find what our next frontier is and push our limits we won’t grow personally. Some people are fine with that obviously, but I’ve always been one to push my limits. Concretely though, I started with 16/8 then narrowed it down to like a 3 hour eating window then just decided I could go all out alternate day fasting. Now I do something like a 45 hour fast with 3 hour eating window, perpetually; and a 72 hour fast once a month.
Not to be argumentative, but I do not fast and I need far fewer calories to get by than I used to. It's because I'm in my 50's ;-). I don't think I'm aging slower than I used to. I think probably I'm healing slower. It's pretty easy to make an observation and derive conclusions that fit your pre-conceived ideas. It's one of the dangers of doing these kinds of self experiments.
Have you experienced additional mental acuity/focus first hand?
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.
Water-only fasting was popular in sanatoriums and weight loss spas in the late 1800's/early 1900's... practice was stopped after lack of electrolytes caused several patient deaths from heart arrhythmias.
Can you recommend any good sources to find out more about this need for electrolytes while fasting?
I have been unable to find articles or books that seemed credible to my uneducated eye.
Sounds like you could successfully fast very easily by eating the same amount of food in shorter period of the day, like 16h fasting and eating in the remaining 8h of the day. Without changing the amount of daily calories you wouldn't experience weight loss.
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.
Eating the same amount of food in a much shorter period is also a great way to train your stomach to accept (and unfortunately, expect) more food before feeling full.
Is that a well-documented truth, or just something you think seems right? The opposite has been true for me for the last few years of sort of informally fasting: I hit uncomfortable satiety faster when fasting.
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.
The Hadza in Africa are an interesting people. Quite a lot has been written about these hunter/gatherers. [1] The have the physiques you'd expect of hunter/gatherers, but not the lifestyle. They work around 2 hours a day in mostly low energy tasks. And their leisure time isn't exactly spent running marathons - the most common past times being gambling and simply relaxing. Part of the reason they've been reluctant to adopt agriculture is because they think it'd take too much work. You can do an imagine search for pictures of their well known people. Suffice to say, you're not gonna find many love handles.
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.
> 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
That must be the worlds smallest slice of pizza. 100 calories is nothing, about 1 apple's worth.
Upton Sinclair reported skinny people gaining weight after they took up fasting. Maybe there's something it could do for you? Also, you won't lose much weight in a week and could also try a fasting-mimicking diet too.
Well, I'll at least agree that fasting is easy. It's a habit I picked up in jail. My ex recently told me that she also picked it up in jail (we were arrested together). I think being in such an environment, with little to no control over anything else, controlling your eating habits becomes a natural way to restore some balance.
What is fasting anyway? Some people tell me they "fast" by drinking no alcohol. Others say they fast by only drinking water and not eating anything at all. Why does everyone have to use the word so differently..
I've also heard it in relation to not eating meat, not eating candy and not eating various other categories of food. Never have I heard it in a meaning of not consuming anything at all, however.
Fasting meaning abstinence from food is fairly well-established. Breakfast is literally break-fast, with the fasting period being overnight while you slept.
> "That sounds to me like a big deal, given that most people find fasting difficult"
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.
44 yo male. DHEA is amazing. In times of stress, it restores my libido and ends my depressive cycle. I don't take it every day, but I definitely keep it close by.
36 year old male here. Using metformin to artificially lower my blood sugar level to help keep weight off and for life extension purposes (asked my doctor for a prescription at my annual physical, said "sure, go for it"). Highly recommend it.
Metformin is fairly safe as far as pharma goes; it requires a high dosage to be toxic, and the primary side effect is gastrointestinal distress. It's also a cheap generic (~5 cents/pill, costs me $2/month). It would be unfair to lump it in with the opioid epidemic, considering the differences.
Would you not at least try to live a bit longer for only $25/year and a once a day pill?
It seems Berberine and Metformin have different activation paths (Berberine might not lead to AMPK activation) and don't necessarily have exactly the same effects. Is there any research on the two being comparable for longevity purposes (other than lowering tumor risk)?
How much are you taking? Do you use it to stay in ketosis, along with Intermittent Fasting, or something else? Is there any good literature for using this outside of it's intended use for diabetes? Thanks!
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.
There is a theory that still needs more evidence that cancers consumer sugar, and reducing your blood sugar (and sugar consumption in general) will slow tumor growth. There was another thread on HN within the last week that fasting 24-60 hours at a time during chemotherapy protects healthy cells while allowing chemotherapy to be more effective against the cancer. Things to discuss with an oncologist. Best wishes for your sister, I hope she pulls through.
I think the metformin was part of a shotgun approach used by the docs at UCSD. My friend's brothers were aggressively pushing treatment when it was clearly inoperable so that may have had something to do with it. My friend lasted a single, horrible year and passed away a few years ago.
I think "easiest" is sauna. Exercising is good because it can also help with your mood and brain functioning. I heard conflicting information about cold shocks. There is also fasting which as top comment said works similarly to original link.
I'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).
Biology 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
Ugh, 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.
I lot of people look at just one part of biology and totally ignore all the basics only focusing on aging reversal and living forever. First, autophagy is nice to have it done from time to time, not constantly. If you constantly activate it, then your cells will reach the Hayflick limit. So, you need to boost your telomerase... but then you can more easily get cancer.
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.
Studies with Rapamycin suggest otherwise. Mice live on the order of 20-30% longer, so for mice, simply inhibiting mTOR is enough to extend the biological age.
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.
If 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)..
Do 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!
The 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.
This is false. We can explain a lot without a placebo comparison. Also, the placebo isn't magic, we just haven't studied exactly what it is. It clearly does have limitations: look at all the studies where the placebo only does so much!
There is more to the sample size than the number 9. Every time unit before the experiment where the effects were not seen is a form of sample. For example, suppose nine old people took an unusual drug and then grew 1-3 inches over the next two years. The fact that it happened right after they took the drug, and not some other point in their life, would be one heck of a coincidence, the probability of which depends on the absolute rarity of that sort of event.
Sure, 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).
Our 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.
Only 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 :)
> 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 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)
The problem is that old species members generally rely on the same resources as young species members. So if you're in a resource-constrained environment, you need to clear the old out.
Biological immortality in plants and animals isn't unheard of.
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.
The life/reproduction cycle of jellyfish makes it difficult to talk about "common parlance" age. Someone even made a website about it: https://immortal-jellyfish.com/
Highly unlikely - statistically speaking, predation and disease would kill any individual specimen long before 500M year passed. That said, there are ‘immortal jellyfish’ that do not die of aging - don’t worry about an uprising though, they can be killed!
>predation and disease would kill any individual specimen long before 500M year passed.
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.
The way it works, to our understanding, is these immortal Jellyfish his sexual maturity and have offspring, or another for of stress (starvation, temperature change, attack, etc...) and they revert from sexual maturity to a polyp stage and restart the life cycle, and unless they are killed they continue this cycle in perpetuity.
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.
No. You're succumbing to the fallacy of group selection. Evolution operates on a gene-specific level. A trait that maximizes an individual's inclusive genetic fitness at the expense of the species will always out-complete.
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.
Wouldn't a gene prefer to transmit copies of itself into descendants that replace all the other genes in the DNA it shares, with better fitness-maximizing ones?
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.
Yes, if a gene's surrounded by copies of itself, then there might be certain scenarios where it will destroy a copy of itself to help other copies of the same gene.
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.
What I'm saying is that "genetically identical" doesn't matter; only the integral of all "contains the particular gene sequence from whose perspective you are analyzing selfishness" considerations matters. Which is to say, it's not the genome that's selfish, it's a population of genes that are all individually selfish, at the expense of other genes in the genome.
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.
If a mutation occurred in an individual such that it would not age, while everything else remained the same, that individual would have more reproductive opportunities and so would its offspring, but there would still be differential success, that is not all individuals would reproduce at the same rate. So you would still have reproduction, heredity and differential reproductive success. So evolution would continue. The fact that all creatures age suggest there is some fundamental trade off between longevity and other types of fitness.
I like David Sinclair's idea that while DNA can be considered digital data, copying it is an analog process and we end up with copies of copies of copies, each a little worse than the previous one, while DNA is still intact.
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.
Wouldn’t that mean there is evolutionary pressure to keep reproducing as long as possible (and so, evolution should lead you to live forever and keep making babies)?
Not sure about the exact math here, but there is diminishing "returns" to the genes with every additional offspring. Going from "zero offspring" to "one offspring" is the biggest jump genes can make. Two is 100% better than one. But three is only 50% better than two. Four is only 33% better than three.... etc
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.
This is only true if you have limited resources and still expand the population by reproduction. When we start colonizing space living forever would not be a problem.
Some 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)
Centenarians 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.
Aubrey 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.
Every 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..
I 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.
> 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."
I 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.
>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.
Can 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?
Because 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.
When 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." ;-)
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.
What 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-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.
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
„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 )
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.
197 comments
[ 3.3 ms ] story [ 285 ms ] threadNever ascribe to racism that which can be adequately explained by your own ignorance.
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
https://www.biorxiv.org/content/10.1101/704783v1.full
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.
[1] - http://rewild.com/in-depth/leisure.html
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.
Does it really mean that if some guy has fast in teenage, he can grow taller or more muscular?
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.
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!
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.
[1]https://en.wikipedia.org/wiki/Turritopsis_dohrnii
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.
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)
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."
That's a significant disclaimer. I wish they'd not even call such things a trial.
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.
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!
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.
http://freshlook.annals.org/2019/08/is-metformin-really-wond...
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.
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
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.