Progress of anti-aging therapies by clinical trial stage

I may be wrong, but I think they are all different forms of clinical trials.

NIH Definition of a Clinical Trial:

"A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes."

A phase 1 clinical trial is used to determine safety (including dosage) and involves far fewer people than a stage III clinical trial.

For Biotech startups, the companies value usually increases with each successfully completed trial. Conversely, the cost of conducting a trail also increases at each stage.

This is a super pessimistic and misleading description of phase 2 & 3 trials; actual efficacious drugs do come out of the FDA review process. Many phase 3 trials are against standard of care rather than placebo and many are longer than a few weeks, particularly for treatments where efficacy is hard to prove.

Ai is hardly hyper inflated. Everything from your phone to cars to planes use ai and machine learning one way or the other.

I already did!

Ironically, if people that care about the planet don’t have kids to save the planet, you will be left with more people that don’t care about the planet down the road

population will plateau

Just let immortal people have no more than one kid. That way the population (of immortals) can double at most.

I don't have interest in having kids. But I guess that if I was facing immortality or the prospect of reaching twice my age I would be even less interested on having kids.

I imagine people with access to anti aging therapies would postpone having children further and further.

maybe immortal people care even more about the longterm well being of climate / ecosystem?

My guess is he is referring to this paper, which made headlines a few months ago:

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028

Is HGH + DHEA available to buy like a supplement? I would have presumed something containing hormones would be more regulated?

sure, I understand that, but from what I saw the data isn’t that hard to process either, there are multiple R libraries actually that help, I’m currently also learning Genomics Analysis Harvard course at edx.org.

I already found multiple papers published in the last few years that identified the important locations with methylation changes, and those targets map to known illneses.

I tried to go to many doctors, but as they couldn’t measure any important changes with their toolboxes, they all sent me to psychologists.

Thanks for offering help, I’m always interested in learning more about genomics, though right now my plan is to learn by reproducing some articles that I read that contain methylation data sets (after the Harvard course).

I’m planning to do 450k or EPIC BEADS chip, not whole epigenom sequencing, as most researchers used 450k chip for finding the interesting methylation differences for people affected by high air pollution. I saw about $500/sample, but if it’s significantly more, it’s not a problem for me, my chronic disease isn’t going away anyways.

Methylation is changes slowly throughout the life, the strongest predictor of age inside the body (that's why it's used as an aging clock).

This also means that it may be the most important thing to learn to manipulate to defeat aging.

Also it's the cause of many non-genetic chronic diseases that come with age.

In summary it's a really really important thing to study.

https://en.wikipedia.org/wiki/Epigenetic_clock#Properties_of...

There are other hallmarks of aging though:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/

They are similar, David Sinclair prefers NMN, but he doesn't have that strong preference.

It's been claimed by some that NR is less stable in the bloodstream and doesn't boost NAD+ levels as much as NMN.

NMN is a B-vitamin derivative.

Hgh works wonders used it for about 3 months and got sixpack doing hardly any workout. Lost all excess fat. Got a better sleeping pattern. Its easy to get your hands on online. Problem is that its mad expensive even more so with a prescription as the stuff without you might get was stolen or a cheaper brand.

I am not saying there isn't a use case for HGH, but you can increase your own natural HGH production through intermittent fasting, l-glutamine, and cycling up/down a few other molecules. I learned this by mistake, from trying to repair damage to my gut. The weird side effect was quite a bit of muscle development and I don't even work out. On top of that, I dampen mtorc1 with Berberine, Sulforaphane, Myrosinase, TransResveratrol, DIM+Quercertin and that should slow HGH production, but has the opposite effect and increases it.

And I second the NMN being expensive. I use about 800mg a day and it is by far the most expensive thing I take.

HGH is a wonder drug, but it's tricky. Not only for the expense factor, but like everything else, when you add exogenous hormones, your body stops producing them.

So if you supplement with HGH for years or even months, your body stops making it and the ability to produce more may take a very long time to come back. It may never come back.

Also, there are many types of tumors that have HGH receptors, and HGH has an even bigger impact on the tumor than it does on the rest of your body. So you're basically supercharging your cancer.

A lot of preventative care just delays old-age care rather than avoiding it entirely.

I remember a professor in law school saying that during the big tobacco trials, someone mentioned that people dying younger from smoking meant lower healthcare costs overall, because the major predictor of healthcare costs is age. Basically everyone dies, and the older you are when you die, the more expensive it will be.

Obviously that's not a good reason to die early, but preventative care is mostly good for quality of life, rather than from a financial perspective.

Maybe it's that I'm mid-career and burnt out, but the idea of getting to be a draft animal for an extra decade is utterly unappealing.

Agree that eating meat at every meal is a dumb idea but is there much difference between a plant based diet and a mediterranean one in this regard ?

There's very little evidence that completely abstaining from meat (animal based protein) brings any meaningful advantages from the perspective of life span. In fact in general, it's far more difficult to build a complete diet eating vegan only. I of course do think there's a moral argument to a vegan lifestyle, and am a definitely a strong proponent on that end.

Personally, I think a vegetarian diet strikes a better balance that's also more sustainable in the long term, assuming that you also do care about maximizing life span as well.

Oh, I don't disagree. There's the entire burgeoning field of nootropics from which you can pick and choose as many supplements / drugs as you could want to test. An interesting point you might find, is that the nootropics which often have the greatest effect are the ones that help to deal with one or more of the items listed above.

For example, looking at some of the most common "life-extending / anti-aging" supplements people use which might hold promise of clinical efficacy:

[melatonin] -> proper sleep (usually there's an underlying issue of anxiety, stress, bad posture, sleep apnea, etc. that's being supplemented here)

[an innumerable count of different micronutrients] -> complete diet (those that see the most benefits are people that have deficiencies in those areas whether due to poor diet or genetic mutations from birth that lower efficiency of production but perhaps aren't so noticeable that they result in life threatening effects)

[metformin] -> intermittent fasting (which really ends up being the process of autophagy that you want to occur)

How do you get a prescription for it if you don't have diabetes?

How would you go about reducing chronic stress? Or are the causes of chronic stress so differentiated that there isn't a prescription you can make?

Also, how did you go about detoxing, in your case?

> most people who are chronically stressed will generally never be able to obtain relief

This really stood out to me. If this is how you feel, I strongly recommend trying out meditation. I at one point in my studies while in college felt the same, and it really is night versus day in being able to experience a life without constant stress/anxiety.

> The same for proper sleep. Its not just about 6-8 hours, its about quality. If you aren't getting quality sleep, most people don't have a solution.

Stress/anxiety from above is generally the most common cause of poor sleep. Fixing that will give quality sleep for the majority of people. The next thing to try is to check with your doctor whether you have sleep apnea as that's probably the second most common trigger. For some, sleep apnea is treatable with better sleeping posture and for others it will require more active work to resolve. A note that obesity is the most common cause of sleep apnea. The third most common cause is likely some kind of thyroid condition. More than that is probably going to be a case by case basis where you'll have to individually look at your genetic profile through something like SNPedia (https://www.snpedia.com/index.php/SNPedia) to try and pinpoint your underlying issue. Usually though, the first three things will cover the vast majority of people looking for better sleep.

> In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting

For most normal people, it's unrealistic to be able to do day fasts. That's why the 8/16 method is so popular. You'll still see benefits as you are incorrect that, there has to be a strict limit of precisely 20 hours to get beneficial effects. Autophagy like any other biological process in the body is a series of continuous interlinking upregulating and downregulating mechanisms that ensure homeostasis. Autophagy is always happening. It's just that the longer you fast, the more your body gets tilted towards consuming/recycling until of course you end up in starvation which is effectively just extreme autophagy.

> Finally "a complete diet", not only is there no general consensus what that is, you generally can't even have a conversation about diet without triggering a flame war.

A complete diet to the best of our knowledge, consists of getting enough macronutrients like protein, lipids, and carbohydrates in addition to an immense number of different micronutrients that while seemingly daunting in size are actually relatively easy to get enough of as long as you eat a diverse mixture of different foods. If that answer doesn't satisfy you, there have been many different studies and current ongoing ones as well to try and pinpoint all the essential trace nutrients the human body needs to survive. From the ones that we've been able to gather over the years, if you were to solely supplement yourself based on those listed, you'd probably be fine. Though it's likely that there would be some things missing.

"In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting)."

I can't comment on how long it takes to achieve autophagy - I am happy to stipulate that you are correct.

However, digestion is a very all-encompassing, rigorous and expensive activity for your body. If we believe that there are more "cleanup" mechanisms than just autophagy, it's not much of a reach to suggest that we engage in extra digestion at the expense of these maintenance tasks.

>As to intermittent fasting, that has become a major fad since the Nobel Prize for Autophagy (with the most popular implementation being a 8/16 time restricted eating "fast"). In other words the goal is to trigger the body to begin consuming/recycling dead cells and other cellular waste; however, this typically isn't triggered by time restricted eating, but requires longer periods of fasting (usually kicking in around after 20-24 hours of fasting).

There's always OMAD (one meal a day). I generally fast 23 hours out of every 24. I rarely think about my next meal until I get home from work and it's time to cook something.

Agreed as to your finale, most people have a pop culture understanding of physiology, but remain vehemently opposed to certain ideas largely accepted by alternative health communities. (And the functions, for those of you still unclear, are many including balancing the blood pH and removing actual toxins from the body.) However, regarding fasting, one of the most recent studies (<1month, dec19) around is pretty compelling.(0) Though the breakdown is 6/18 vice 8/16 and it seems they do advocate for a weekly fast of 5/2 days (eat/fast). How's that for a weekend?

0. https://www.nejm.org/doi/full/10.1056/NEJMra1905136

I'm sorry to disappoint you, drugs (defined by the simple macromolecules we know them to be today) can supplement your body in doing only what it is already capable of.

Increasing lifespan more than that requires an entirely new paradigm or class of therapeutics. Like you said, we'll need entirely new biological/genetic technology to address the system-wide mutation and degradation of the body that inevitably occurs through the progression of time. That requires going into the realm of biotech/nanotechnology/etc. which as of now, we are still very far away from being able to produce. It will require many more years of basic research in a plethora of different fields before we can even begin to think about it in fact. Your best bet if you want to make it all the way to then is to follow the steps listed above.

If I'm healthy enough to keep working, retirement isn't really necessary.

Also, given enough time, I ought to be able to amass a self-sustaining pile of wealth and then I can retire :)

This is technically true, but once you plan for a 60 year retirement, going out 90 or 100 years is not as difficult as lasting the first 30 years.

I think withdrawing 3% a year would have lasted you the entire time since the 1880s (last 140 years of the stock market)

Where can I find more about this?

Other than the condescending tone, this comment is probably worth keeping.

summary: there are extralegal, cheap, and convenient methods of collecting supplements/drugs that will be available to everyone with a credit card and the right risk tolerance, regardless of e.g. FDA approval.

Great, so the advice is, "Take a drug, compounded in a foreign country with different/more lax regulations, for some hypothesized, 100% unproved reason, without a doctor monitoring it."

Good luck.

Aware of what off label is, thank you, but I think you grossly misunderstand modern medicine if you think a doctor is going to prescribe a drug originally approved to treat cancer because you _hypothesize_ it might have some anti-aging properties.

That's the whole issue with this list: none of these trials are testing the anti-aging hypothesis - it's just mentioning particular pathways -like Wnt (a core development program and implicated in many, many aspects of human health) and saying that the drug would be anti-aging.

As for "unethical" - well, yes, the person would be unethical since they would likely being prescribing a drug for no reason, with no basis, based solely on misguided patient belief. This is more likely to endanger the patient than it is to help. Thus, unethical.