It's not all that hard to try to be honest. Some people have reported absolutely massive changes, some small, some little to none. One or two said decrease but there seemed to be maybe some valid external factors for that.
That's about the distribution one could expect if mitochondrial damage was at play and there was an effective solution for it. Not everyone is going to respond well, likely the older the better if it actually is doing what it says on the tin.
At the very least, it's intriguing and out of all of the thousands of pages of medical literature I've read over the past half decade or so it's been one of the more interesting sagas to follow.
At a cursory glance, it seems like the biohackers may simply be poisoning themselves on "fission" days and riding the rebound— eventually habituating to the fission supplements (a la arsenic eaters) so they feel less bad on the fission days (which they attribute to mitochondrial repair).
It is safe doses of well-known supplements (and works for other swaps in their classes -- like apigenin, sulfurophane, etc).
Curious to hear though the thoughts on the poisoning line.
I definitely didn't mean to imply that I necessarily believe its poisoning. Apparently the neurotic and anti-interventionist in me reared its head when reading the thread.
I didn't recognize any of the supplement names, and so I didn't realize they all had reasonable safety profiles.
I think my point still stands though. From what I saw, the outcomes were deemed positive as a function of subjective reports of well-being, without controls. It seems very possible the protocol is having any range of effects (from negative to null to positive)— I just didn't see anything other than placebo-uncontrolled anecdata.
This is not to discount their efforts! I am truly interested in the subject.
Is there anything similar in the science of anti-aging? Where (A) The body of research is large, well established, and mostly uncontroversial; (B) The benefits and safety profile are good; (C) The majority of people who are serious about this stuff use it/take it/do it.
Most of the interesting stuff happens when you focus on just A part: Yamanaka factors are both super powerful, established as reversing the probably most important hallmark of aging and super dangerous (causes cancer) at the same time.
What's promising is the pace of research: in 20 years there's a good chance to have real safe anti-aging available, but we still need to survive until then.
I've seen some of the discussion about/around the Yamanaka factors and it feels like an anime plot point, honestly. I need to look more into them and understand them a bit better. They're the ones implicated in stem cells returning back to pluripotency, right (and then the long deep dive about DNA damage/repair/what the heck is happening in the disparity between repairing damage for reproduction vs the everyday repair, etc...)?
Altos Labs being funded is both a blessing and a curse, because it funded the best researchers in this area with hundreds of millions of dollars (5-10x their salary in what they were making as university professors), but since it was founded, there are much less publications available.
Do you mean "don't eat excess fat" or "don't have excess fat on your body"? It's not clear to me from the context.
There have been already studies showing that body fat percentage is a better predictor of mortality than BMI, but most studies focused on BMI in the past, as it's easier to measure.
It's pretty obvious older people who have kept their fitness (cardio & strength, not just one of the two) up and their weight down their entire lives have profoundly higher quality of life.
That requires a totally different lifestyle from the standard "geek lifestyle" though.
Hopefully we can improve that. Many people would be much more okay with feeling great up until an old age, have a few weeks of infirmity, and then pass away rather than the multiple decades of gradual decay that we have now.
Not that that's necessarily entirely realistic or possible, but it would be nice, if it is a possible thing indeedy.
Nutrition is difficult to get right because of the contradictory and plain harmful information that we have been receiving for so long.
For example: is fruit juice "healthy"? Not really, when you consider that you are far more likely to consume way more fruit that you otherwise would, and a lot of fiber content is removed. We are unlikely to eat 10 oranges in a row, but that's easy in juice form. That's without extra sugar - if sugar is added, then it's just a soda with added nutrients. And the problem with that is that fructose is only metabolized by the liver (turning into triglycerides), with a mechanism that's comparable to the one used to metabolize alcohol.
We have been told that fat is bad. Due to consumer demand, the industry start removing fat content. But then things taste horrible, so the solution was to add sugar.
So now we are worse off: not only we are consuming a lot of sugar (75% of all products in the supermarket have sugar, including 'salty' ones), but we haven't even attacked the problem that prompted fat removal (increase in heart conditions) in the first place. Fructose in particular turns into triglycerides, and gets stored as fat(with uric acid as byproduct, with way more free radical formation than glucose, and it even uses up ATP). It didn't address the heart issue, and actually made it worse. People have become far more obese than when they ate fats, as fats (plus fiber) make you feel full for longer. It also screws up hunger hormones and sugar is addictive by itself.
Or let's take bread. White bread is starting to get considered harmful, but then the alternative that's pushed is whole bread. It matters very little. If that's all we ate, we could have some bread, as our ancestors did. But in combination with all other crap, it's way too much sugar.
If you eat cereal for breakfast, some rice and beans for lunch with a glass of orange juice you have already exceeded dietary sugar limits by a lot. And that's a far, far healthier diet than what's done in the average household.
Whereas if you had an avocado for breakfast, meat and vegetables for lunch you would be in a far better shape (literally and figuratively) even if the second diet had more calories. Calories are not all the same, and calories contained in food are not the same as calories absorbed (or stored). We accept that, when we fuel our car, a bunch of energy in the fuel will be wasted. Somehow, when we count calories, we assume we'll absorb them all.
The end result is that we are prematurely aging (due to all the oxidative stress), getting diabetes, non alcoholic fatty liver disease, high blood pressure, gout, cardiac problems. Possibly even Alzheimers (research ongoing, but there's growing evidence) and a few types of cancers. Also oral health in general. Basically, most of the mortality these days is directly or indirectly linked to sugar and insulin resistance in general. 88% of Americans have some form of metabolic dysfunction.
> no excess fat
Too much fat is usually the symptom of a disease (generally metabolic illness). Just fat, by itself, can be ok(also depending on where it is) – there are fat people who are otherwise healthy (a tiny minority, but they exist). And there are people that are thin but otherwise unhealthy (TOFI, Thin on the Outside, Fat Inside). What commonly happens is that we get sick first (insulin resistance) and then we get fat. For most people, being obese is the symptom, not the cause.
Diabetes does not strike out of the blue, although if you ask most people, they got "surprise" diagnoses. You check your glucose levels, and they are normal. You keep checking them for a few years, they are normal. Then "out of the blue" they are outside limits, and you get a diagnosis of pre-diabetes (or full blown diabetes). What was missed all these years was that your body was fiercely fighting against the glucose increase by raising the amount of insulin produced. But there's only so much the body can make (and also the cells will be resisting that), at some point, the combination of not being able to increase production plus resistance will be too much to overcome. Insulin measurements are not part of standard bloodwork yet, but at least they are now including A1C.
Completely drop added sugar. Reduce sugar in all forms, added, "natural", it doesn't matter. A sane amount of fruits is ok for their other benefits. Increase the amount of fat and fiber. Hydrate. And then drop processed foods in general. That's how we survive until 'anti-aging' is available.
> Completely drop added sugar. Reduce sugar in all forms, added, "natural", it doesn't matter.
One of the hard parts of aging stuff is how nonlinear it is. A lot of the good drug treatments seem to be short term/cyclical, along with significant lifestyle modifications.
In addition to what the other commenter said, I've heard of OMAD and having a strong community/having a purpose or something to do as another strong factor in longevity, in the 90-100+ year olds in Japanese community for example. I can't remember if OMAD was correlated to that community or a different study, however.
Health aside, it is hard to stress how much better I feel on ketones, relative to carbs.
Research in humans suggests that metformin can impact mortality. A meta-analysis published in 2017 that included 53 different studies concluded that metformin reduces all-cause mortality and diseases of aging, independent of its effect on diabetes.
Also, combinations of Metformin, rapamycin and resveratrol, and NMNs.
Davis Sinclaire is probably the leading expert on those, now. He is professor of genetics at Harvard.
(A) The body of research is, in general, large and uncontroversial.
(B) The safety profile is good. The benefits for diabetics are certainly large. Probably no drug has been studied for anti-aging effects as extensively as creatine has been for fitness applications, so I'm not sure anything can fulfill that criteria. But it seems like the present research on metformin supports a variety of positive effects for non-diabetics with more on the way.
(C) I wouldn't know whether the majority of people who are serious about anti-aging use it but it does get mentioned a lot.
Pretty positive endorsement overall!
> A number of studies assessing adherence to diabetes medications in patients with type 2 diabetes have reported that metformin has the lowest adherence rates when compared with other OAAs.
If it's due to its ability to reduce blood glucose levels, then berberine may be another way to get a similar effect.
Berberine stimulates glucose transport through a mechanism distinct from insulin
https://www.sciencedirect.com/science/article/pii/S002604950...
Efficacy of Berberine in Patients with Type 2 Diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/
It also lowers cholesterol
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
https://www.nature.com/articles/nm1135
But pure berberine is not well absorbed in the intestine, so you need to buy a good formation for it.
Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine
https://www.ncbi.nlm.nih.gov/pubmed/20237966/
Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
https://pubmed.ncbi.nlm.nih.gov/24607213/
The best thing might be to cook with barberries:
https://thecaspianchef.com/2020/01/18/zereshk-polo-saffron-b...
The sodium/potassium ratio, and particularly keeping it smaller. The top answer right now is "nutrition", but that's a hairball, and the Na/K is a bright spot that gets left out of the discussion precisely because it is much less controversial than the endless debate over macronutrients and staples. The sodium/potassium ratio has effects on:
hypertension: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....
stroke/CVD: https://bmjopen.bmj.com/content/6/7/e011632.short
bone density: https://academic.oup.com/jcem/article/87/5/2008/2846608
chronic kidney disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047877/
and even such seemingly unrelated conditions as depression: https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy...
and age-related cognitive decline: https://www.sciencedirect.com/science/article/pii/S258979182...
Potatoes and other starchy vegetables like squash and plantains have significantly more potassium than grains, but it's not necessary to completely give up grains. I usually put a 50/50 potassium/sodium ("Lite") salt on the oatmeal or grits I make for lunch (work requires speed), but I don't bother with it otherwise.
Honestly hard to say, because that doesn't immediately "disprove" it either....
https://pubmed.ncbi.nlm.nih.gov/19741313/
To be clear, no one is arguing that Creatine causes hairloss, simply that it exacerbates hairloss in people with so called androgenetic alopecia.
I recall a study that was set to try and replicate these results, but I worry that it was impacted by COVID. If anyone else can find it, I'd be very interested to see it.
(see the rating + probability of positive effect charts here. [Warning, this is another insane rabbit hole of research to fall into!]): https://troof.blog/posts/nootropics/
My heuristics researching supplements, nootropics, longevity, are that the lab-created substances are more often than not, new and poorly studied, leading to eventual realization of more harm than they treat. Most recent, to me, was Alpha-GPC causing strokes.
As far as cancer goes, basically half of the solutions here will cause cancer. That doesn't mean they're bad. Anything involving the body is extraordinarily nonlinear, so extrapolation is extremely hard in a variety of circumstances. You can find a study involving almost everything you consume and take linking it to a variety of things, it's just whether or not it's relevant to people in the doses and in the duration that they take them.
Especially on the cancer side of things, that's just a very delicate matter to be handled. Cleaning things up in theory should reduce the risk of cancer overall, even if ingredients on their own at some dose could cause issues.
A lot of these compounds have been around for or have been studied for 40-50 years or so. Some of the long-term effects are harder to pinpoint, but I'd be careful in seeking too much caution (in the same way I'd encourage someone not to go headlong throwing stuff into their bodies for no good reason). It's really easy to find nonlinear red lights for almost anything in medicine, in my (albeit limited) personal experience.
I can give an analogous example.
Lengthening telomeres is a naive strategy some chase for longevity. You can think of telomeres as aglets for DNA -- they shorten as you get older. So inhibiting that shortening is good, right?
Well, that does extend life, in a way, but it also slows down DNA repair and makes that a harder thing to access, because now damaged DNA has longer end-caps on it too.
So of course a few years after the whole "Just take telomere lengtheners!" headline wave, another headline wave of "Telomere lengtheners actually can worsen aging!" is a decent followup to expect (something like this happened IRL IIRC).
You can make a similar analogy with stem cells and a limited stem cell pool (do you deplete the pool early, assuming it no longer regenerates at this point, for a boost of apparent vitality, or ration it over the course of a lifetime?)
Homeopathy on the other hand assumes a bizzare, quantum-like "memory" in molecules that has not been shown to be accurate by science, but excels as being a placebo effect.
These are quite different phenomena. It's another way of saying "the dose makes the poison", though in this case, it's "the dose has varying and highly state-dependent effects within a strongly chaotic dynamical system".
For now, I'd rather bet on very clean air, very clean water, fasting, organic vegetables, green tea, omega 3 fish oil, well monitored sleep, and lots of exercise for longevity.
Maybe an analogy to communicate the concept is that it is like putting a car up on jacks and taking out parts to repair another part. It's not where you are long-term, or ideal to do extremely frequently, but it's important to keep the thing maintained and running.
That said, I agree very much on your last sentence as one of the best "simple" routines to get bang for the buck. My thoughts would be weight lifting specifically, chamomile tea at night (apigenin is something else), as well as some broccoli sprouts for NRF2 in there. Other than that I think that's probably the index fund-like strategy to longevity, so we're definitely on the same page there. :D :thumbsup:
Not everyone needs NR necessarily (or any of the other forms), but it does seem to get more important as we get older and our ability to manufacture NMN goes down (IIRC that's the main target that's limited here?)
So yeah, they both are kind of similar in that dimension.
In any case, it grabs onto free glutamate, and, whammo! less glutamate, instant glutathione. quite the nifty trick.
has some interesting data/studies backing it up, and also has some great psychiatric effects as well. IIRC it's used for schizophrenia among other things.
If something else is helping the tumors grow faster than the body can kill them naturally - then it's going to result both more severe tumors AND more tumors in general (as we discover them, since we usually don't know about tumors that form and get destroyed by the body naturally).
I think IIRC that the crosslink breakers (referring to AGE above for those OOTL) mainly struggle from delivery being difficult? Because many of the AGEs we care about can end up in some bizzare, hard-to-reach places? I think?
I don't think this is directly related but there was one therapy for cellulite that just had an enzyme that dissolved collagen. I just learned that they (sadly, in the long run for the research field in that area) had to shutter that after only two years or so, apparently due to the bruising and discoloration of skin long term (https://investor.endo.com/news-releases/news-release-details...). I guess I can only feel so bad as they were marketing pretty heavily to people who were rich enough to pay for the cosmetic surgery out of pocket, and were as well in a category of middle-aged "luxury" buyers (from the official website -- I don't think the wayback machine will show the pictures [warning, very butt focused], but perhaps for the better, the saved version has the desktop and mobile transcript. Confetti for a medical drug advertisement website. Incredible: https://web.archive.org/web/20210124142605/https://www.qwo.c...)
Lipofuscein I'd love to learn about, I have not heard of that before.
And it's lipofuscin, I mistyped it. Basically oxidized junk molecules that never seem to get broken down and just accumulate within the cell with age. Interestingly, piracetam seems to have a positive effect on this in rodent brains.
This is why you see so many promising longevity studies in mice that don't replicate in humans. Mice are not particularly long lived compared to humans, so it's much easier to extend their life spans.
The Interventions Testing Program (ITP) by the NIH, which has been testing substances for their effects on lifespan for over 15 years, is regarded as the gold standard for testing possible lifespan increasing substances. Rapamycin has outperformed every other substance they have tested, by a wide margin. There is only one other substance they have tested that has shown a median and maximum lifespan increase, for both females and males, that being acarbose. The greatest lifespan increase observed in any of the trials was seen with the combination of rapamycin and acarbose.
All of the substances that NIH ITP have tested with their results listed, as well as the interventions they are testing now: https://www.nia.nih.gov/research/dab/interventions-testing-p...
List of the substances they have tested with charts showing the relative increase in lifespan: https://phenome.jax.org/projects/ITP1
If you want to start down the rabbithole (SENS talks can be trusted and are good, well-backed by science, etc etc. Have been derailed by some drama recently, but still, they've really done a lot) then you can start by going to the rejuvenation roadmap: https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/
A little further (Aubrey de Grey, from SENS originally): https://www.ted.com/talks/aubrey_de_grey_a_roadmap_to_end_ag...
If you want to lose 4-5+ hours (minimum -- think TVTropes level of rabbithole addiction here), then here is your next free joyride. It's a fun one, I've been pretty interested in it as it's continued to have developed. Have fun reading the saga: https://www.reddit.com/r/sleephackers/comments/ohfetn/turnbu...