The actual paper is here [1]. And it’s not quite as conclusive in mammals yet. But it sounds like there is a clinical trial to actually study the supplement, which is a welcome thing in the anti-aging world. I’m happy to read that this work came out of the Buck Institute in Novato, which is a solid research institution. It’s also a beautiful campus.
Disclaimer: I was there for a short stint as a postdoc a while back and not connected to this paper at all.
That articles says "Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging."
But there is no citation for this statement. Any idea where to read about how these levels change naturally?
I went down this rabbit hole a little. It does seem like the specific formulation of AKG may matter. The commonly available supplements are L-Orthinine Alpha-Ketogluterate (OKG) and Arginine-Alpha-Ketoglutarate (AAKG).
The study in question used Calcium Alpha-Ketoglutarate (CAAKG).
There are a few sellers of CAAKG, but it is an order of magnitude more expensive than the others. (~$1.50/gram for CAAKG vs ~$.08/gram for OKG and ~$.05/gram for AAKG)
There have been studies in the past (for non-aging conditions) that have demonstrated a difference between OKG and AAKG, so it's reasonable to assume there may be a difference between CAAKG and the others as well. Without a study, who knows.
Also as other commenters have mentioned, the only evidence so far for aging related benefits is in mice. Of the human trial studies I could find for OKG use, it does seem like there were no reported side effects, so it might not hurt you, but it also might not do anything for you.
And with a single giant ear on their back. Don’t forget the giant ear.
(Weirdly, just saw a breathless article talking about how 3D bioprinting obviates the use of rib cartilage that the human-ear-on-a-mouse 25 years ago was also supposed to end).
Epigenetics is fascinating. I just came back from a project meeting, where i work with people who discovered that HRT (hormone replacement therapy) slows down epithelial cell aging. Epithelial cells are the cells that cover all your vital organs, so they are important for aging.
Now, there are even commercial companies that measure Epigenetic age of cells with a technique called DNA methylation.
DNA methylation is not a technique that can be applied. It is a biological system present in your cells silencing expression of genes that are not useful for a cells current behavior. Differently differentiated cells have different "genes methylated" and thus inactivated which govern their behavior and potential for further sub-differentiation.
Indiscriminately "reversing methylation" would probably lead to a lot of "cancering".
You don't apply DNA methylation - it is the basis for measuring epigenetic age. I mentioned HRT as one way of reducing epigenetic age for epithelial cells.
The reference you gave measure blood or urine samples which would probably not be representative of epithelial cells. Also i like non-descriptive but professional looking stock photos of multi-pipettes and the ubiquitus vortex genie 2. Extra points for consecutive photos of the same tip-rack in obviously proffessional use.
Not sure riding high on dirty test (dosing TRT levels off toilet test going around gyms will be next to impossible) will slow down ageing - but it will probably make you juicy. Make sure to hit the gym to double the gainz.
I'm getting somewhat interested in this topic. How did you know about this trial? I'm curious what good news sources are to follow so I can see when the results are out.
For anyone interested in the topic, I'd encourage reading "Lifespan" by David A. Sinclair. As someone with little to no-knowledge about aging (other than feeling the effects of aging on myself) I found it very instructive on how our aging clock works and what are some of the ongoing studies to slow down or revert aging.
Sorry, but he oversells his work. He has not contributed so much on epigenetics, but rather nad as a supplement. He oversells nad as a longevity aid.
However, he advocates intermittent fasting, and i heard from a epogenetics research leader that there is an ongoing trial for intermittent fasting reducing your epigenetic age. So sinclair is not wrong on that, probably.
You can do this at home, except for the little inconvenience that growth hormone is a scheduled drug. I wonder what the results would be with just growth hormone. Let's ask Sylvester Stallone[1] who looks great for 75 and got caught trying to get into Australia with illicit Growth Hormone a while ago[2].
According to that paper it doesn't have a significant effect on the performance during exercise but it has a large effect on the serum level of GH. However it should be noted that this experiment was conducted on young healthy men and I have no idea if Niacin have the same effect in women or older men.
Growth hormone can be injected subcutaneously. They now come in convenient pens with adjustable dosage that are so fine you can't feel the prick. But yes, they must remain refrigerated.
90 is still an exceptional lifespan even if you take care of yourself. Human system breaks down randomly after the age of 70, and the complete breakdown depends on luck.
I’m no fan of death, but death (by natural causes - age, sickness , accident) has been how different generations have gotten rid some of the worst despots.
“The hate of men will pass and dictators die. And the power they took from the people will return to the people. And so long as men die, liberty will never perish."
I was expecting the article would be about nicotinamide mononucleotide (NMN)[1]. "Lifespan..."[2], a book on the subject, and more recent publications also mention rapamycin[3][4][5] and metformin[6][7][8].
Did they continue tracking health effects years after they study ? It’s possible the drugs reversed the body clock but will accelerate it after. Much like coffee gives you a temporary boost, then makes you crash later
It was a great validation, that reversing epigenetics is possible in the human body, but using Yamanaka factors to do the same thing has much more investment dollars behind it (billions vs millions), so I believe it will be ready on the market faster.
Are you really comparing Theranos to the Nobel prize winning Dr Yamanaka, and the amazing group of scientists who have put their lives to work on cellular reprogramming?
Of course it's more than just about money, it looks like it's the more efficient path, but there's a huge need in research to stop cells from losing their identity during partial reprogramming (and cause cancer).
I think both approaches are amazing advancement for humanity, and I wish Greg Fahy would get more funding as well.
Before Jeff Bezos came in, the money was really really missing from the longevity field that I have been following for the last 10 years since I've got a serious rare, but not deadly cronic illness.
Maybe I've got a bit sad when you refered money as not the most important thing, because Gregory Fahy said during an interview that they had to stop the experiments because of lack of funding. They needed a few million dollars to run the experiments, which is nothing compared to the value they can provide compared to rejuvenating people. I was thinking of investing personally, but I'm too small to be an investor myself.
Altos Labs being created is a huge deal, because when the technology works (and at this point there's no reason why it wouldn't), it can save the lives of literally billions of people. Maybe it's hard to see through my comments, but I truly care, and I'm hopeful that both of us (you and me) will be able to use it.
It is not just money, but liberation of creative people from the bureaucracy and limitations that come with the public grant system.
AFAIK the professors in Altos Labs get a million dollars yearly salary and they are free to dig into whatever matter they find interesting, as long as it is somehow related to biology of aging, rejuvenation, regeneration etc. No need to stay within relatively narrow limits of an approved research topic and produce X papers in a year.
I didn't think about that part being a slowdown. The only interview I was able to find is that they are building a completely new lab in UK this year (one of the multiple locations), so it takes time to ramp up experiments.
I'd love them to be more public about their plans. mRNA / viral delivery needs to be optimized of course, but there are lots of other parallel experiments they can start, and we probably have to wait for the publications.
I agree that having absolutely no money means you cannot do research of any reasonable magnitude. That doesn't mean that money has anything to do with how correct you are :)
> I'm hopeful that both of us (you and me) will be able to use it.
> Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests.
Presumably the "epigenetic clocks" are correlated with age, but it's not clear if changes to the epigenetic clocks causes aging, or aging causes changes to the epigenetic clocks. (Maybe it's both?) Is this like overhauling the engine in an old car to make it function like new, or is it more like rolling back the odometer to make it seem new?
Exactly. And this is why the FDA won't approve drugs based on changes to biomarker (which is what these "epigenetic clocks" are) unless a direct link between that biomarker and a beneficial outcomes has been proven.
'The FDA’s eventual decision to ignore the advice of its advisory committee and approve the drug, it says, was based on aducanumab’s ability to lower levels of amyloid plaques in the brain — protein clumps that some scientists think cause Alzheimer’s.'
...
With aducanumab, the agency has shown that it is willing to push the paradigm to a broader set of people. One reason that decision has attracted criticism is that decreased levels of amyloid plaques are an unvalidated and contentious marker of a drug’s activity.
In large trials of other Alzheimer’s drug candidates, amyloid lowering has not led to cognitive benefits, and this has made it a sticking point for researchers.' [0]
Indeed! The Alzheimer’s drug was an Accelerated Approval. Basically conditional, based on a “likelihood” that the biomarker is indicative of a benefit, but requiring further study to prove benefit.
I wonder if those amyloid lowering drugs could have a prophylactic effect while having no curative effects. I would love to see a trial in people at high risk of Alzheimer...
If a cheap, reliable technique of halting or slowing down the "epigenetic clock" hits the market, and assuming its main effect on a population level is increased life span, wouldn't it make the demographics of most developed countries even worse?
It's still unclear whether or not "automation" will compensate an ageing population, and prevent a demographic collapse. But having a pill that makes people live longer (even if it's 5 to 10 years), wouldn't it be like throwing an entire gas station into the fire?
If an ageing population has increased health span, they will also be able to work and contribute longer. "Population growth has declined mainly due to the abrupt decline in the global total fertility rate, from 5.0 in 1960 to 2.3 in 2020. The decline in the total fertility rate has occurred in every region of the world and is a result of a process known as demographic transition." [1]
My personal preference is to replace Metformin with Berberine since I can get it online or grow it in a greenhouse and it is less likely to induce lactic acidosis. One can fast for 72+ hours to get a massive spike in HGH. I am not a doctor and this is not medical advice.
I also consume desiccated Thymus in capsule form following the "like improves like" theories.
Here is a video discussing the latest results the article is talking about [1].
referenced articles therein say fasting 48 hours causes a 5-fold increase in HGH, fasting 5 days causes a 10-fold increase, but that 5 days of fasting also makes the cells unable to utilize the extra HGH:
"Despite the fact that fasting may increase your growth hormone, it actually suppresses the anabolic effects of HGH. That’s because fasting lowers the sensitivity of your cells towards HGH, and decreases its main anabolic mediator called Insulin-like growth factor 1 (IGF-1).
Thus you will not experience the benefits of increased HGH on muscle mass, energy levels, etc. ..."
Agreed. One has to cycle the fasting / exercising / rebuilding. Each trainer and nutritionist appear to have their own preferences to maximize this effect but they also have many confounding treatments and are usually already quite healthy.
I would suggest researching this more on the PubMed nih.gov site as they get into a little more details and usually have decent controls in place in some of the studies. Their search function is awful so I suggest using the following on google to get better results:
I use these and many other molecules so my answer would be far from scientific. Anecdotally I can say that I heal faster than anyone I know of at or near my age. I also look and feel younger than anyone I know of at or near my age. I do not get sick and have no age related pain. There are too many confounding processes and molecules to attribute my results to these specific things however.
Because the process is ‘dumb’ (as you put it) we evolved via chaos rather than order. It therefore follows that how we work is complex and disordered - and an easy ‘cheat code’ doesn’t exist.
This is at best eternal youth, not resistance to all injuries and illnesses.
We’d all still die at some point — at current rates, even without ageing, 0.1% would die in any given year, though it isn’t clear how that would change long term — we just wouldn’t get age-associated degeneration such as Alzheimer’s and forget the concept of left and how to count past four like my mum did: https://kitsunesoftware.wordpress.com/2018/01/31/alzheimers/
I don’t know what you’re imagining that makes you see a nightmare.
It's an interesting point. I forget the exact quote and source, but
it's something like: living to a very old age requires great emotional
strength, and is lonely, because you will see all those you love die.
Getting to know your grandchildren and embrace their changing world is
probably a good defence in this regard.
To the extent I agree with the parent commenter about it being "a
nightmare", the danger lies in exacerbating inequality. As with all
medicines, those with access to life-improving medicines will be first
world, wealthier people.
But of course that's no good argument against progress, just an
unfortunate short-term side effect of it.
> If we lived forever I think we would all become more and more anxious and excentric as time progressed and our souls inevitably became more "scarred".
Not sure, you could apply the same reasoning to people who go thru active wars: the first time they see someone die, they care, but by the time they see hundreds of people dead it does not matter to them anymore.
I tend to agree with you. In saying that, I wouldn't mind an extra 100 years. If we could invent a mechanism to avoid concentrated power/resources [1], I think humanity would be better off; for if we can mostly agree that "with age comes wisdom", we would surely be collectively wiser.
[1] - The mechanism to avoid concentrated power is a drop in for many other things. For example, I believe if societal structures could effectively optimise for ethical behaviour, individuals would be less likely to crave for power lust and greed.
I do not believe it is always a nightmare. If one plans for a long health/life span and is always adding forms of diversified income then it is just a matter of hobbies.
One of my personal goals is to tell the great grandchildren of people my age what their great grandparents were like since most of them won't write down the interesting bits of their lives and instagram/snapchat/facebook leaves a distorted image and may not even exist in the future.
I like to look at it holistically. If you don't want to live forever, your life is a rounding error anyway. May as well die today. Don't want to do that? Why do you imagine you want to do that in ten years?
I don't understand fearing immortality and wanting to actually get old. It's a common theme in silly trite science fiction but never seen a good argument for why it's something to fear.
Depends on how you'd define 'immortality' in your though experiment.
I'd actually disagree with you - under the premise, you'd be able to end your life as you will.
In that case, hell yes, I'm in for that. I'm in my mid 20s and the past years have been filled with burn-out, depression and literal still stand career-/ education- wise. I can now really grasp how short life actually is. It's so easy (I did it!) to actually waste a notable portion of your life span.We're talking more than half a decade. It gives me shivers. I have so many interests and I'm never bored. I can find interesting topics in any domain and if I could, I'd stay in university my whole life. So, to make this short, I'd be the ultimate dream of mine to not have to care about what to fill my life with. It steamrolls me and I get a lot of fear out of it. But not the fear that drives you, the fear that paralyzes.
Since there are people who end their own lives early, i.e. suicides, that position is clearly not unique.
But I think it boils down to where you are in life. No-one would like endless suffering.
As for my own stance on this, i wouldn't want this to happen simply because it will greatly exacerbate the gap between the haves and have-nots, the poor and the well-off. It will completely throw the current social equilibrium out of the window.
And I'm mainly talking about life extension, since i find immortality a foolish/impossible goal.
Altered Carbon, and to a lesser extend Upload! touch on this dystopian part - the great leveller is that every billionaire will one day die - imagine if that wasn't the case, and they could keep hoarding wealth and having undue political influence.
Would you really want your parents to die, your loved ones, your family, your children, and yourself, all so you could have the satisfaction that at least rich people, and their loved ones, would suffer and die too?
Many people are fundamentally motivated by fairness, and knowing someone else is getting more than they seem to deserve can violate that. Schadenfreude is a thing.
Myself, I think that longevity treatments are unlikely to remain unaffordable to the poor for very long after they are invented — even in a cynical world where the rich are greedy enough to try and keep it for themselves, old-age healthcare is really expensive, so societies which cause this to be cheap will outperform those that keep it for just the powerful.
I suspect that in any society where this exists, the government will end up making it available for everyone... or will be voted out / overthrown for a government that will.
The individual rich are irrelevant, and this is a mischaracterization of the sentiment.
Elite capture under the parameter of current human lifespans is extant and difficult to counteract. It stands to reason those negative consequences associated with elite capture would only be exacerbated under longer lifespans.
It’s simply an acknowledgment of a likely negative consequence.
If you take a step back you see that when they currently die, someone with roughly their money takes over. Good families keep generational wealth, so you will always be under the influence of some rich person. It is our modern royalty after all.
Given that is the case and everything else being equal, I would prefer that exact scenario with an opportunity to live forever. Even if that means someone I don't like gets to try that too.
HN is the only place where I’ve seen people purpose immortality as a legit goal. I think it’s because of lack of religion. If you are existentially scared of death and you are a techie, it makes sense
Not to self-own or anything but I'm religious and lots of religions have a message of immortality for the virtuous, e.g. Christianity, Islam. But our method of achieving it is spiritual, not technical. I think pretty much every normal person fears death right up to the end, unless they're seriously suffering in their body.
That's "opiate of the masses" claim, but rather its removal of suffering and imbuing life with permanent meaning and purpose which isn't lost at the point of death (theosis).
What is the point and purpose of life, beyond avoiding suffering and seeking pleasure? Even the ancient pursuit of honor and memory is rather ephemeral and lame.
> imbuing life with permanent meaning and purpose which isn't lost at the point of death (theosis)
That's generally how most people define imortality.
If you take that + remove suffering, it is one hell of a carrot.
> What is the point and purpose of life, beyond avoiding suffering and seeking pleasure? Even the ancient pursuit of honor and memory is rather ephemeral and lame.
That is something we all have to discover for ourselves. Many people find that through religion, and as long as they aren't hurting others i don't begrudge them of it, but there are lots of paths to finding existential meaning.
I mean, i have no idea about what religion you follow or what its views on the afterlife are, but generally speaking, having some sort of spiritual/soul afterlife usually means having the good parts of physical life without the bad parts.
Nobody wants immortality because they miss being constipated.
If my quality of life remains high and I can still choose to end things when I want, I don’t see an issue. Then again there’s probably psychological cost and I may end up a sociopath
So if I am understanding this right, this is turning back the epigenetic clock but not rejuvenating the individual? So it could help prevent aging but not reverse.
As we age does our body act differently to make life easier as we get older? If so could this make life worse?
1) There is no "epigenetic clock theory". There is an epigenetic clock though, and it's a well established system[0]. They are talking about measuring a cellular "age" by measuring the methylation/acetylation tags on DNA and histones. These tags are essential for specialized cellular function and a core part of Horvath's/Sinclair's "epigenetic theory of aging".
2) Sinclair is not a quack, and to depict him as such doesn't help whatever opinion you're parroting. The guy has quite the resume, and obviously playing the social media game doesn't mean you should dismiss that.
3) Linking a tweet that essentially says "no you're wrong" is adding to the noise and isn't helpful. Brenner is saying reversing epigenetic age isn't going to make you immortal, which is true. It doesn't mean Sinclair's work is BS.
Follow Brenner for a while on Twitter and you'll come to realize most of Sinclair's public claims are pure BS.
> There is no "epigenetic clock theory". There is an epigenetic clock though
Well, there's an epigenetic clock wikipedia page, but yes it's a theory that those epigenetic markers are meaningful indicators of age. Except there are pro-aging molecules like hGh which reverse some of the epigenetic markers despite being pro-aging.
I don't know man, I'm just a SWE, so I'll leave this to the PhD's, but clearly many of Sinclair's claims are false, similarly to Dr. Huberman. A lot of SiValley folks have bought into their futuristic promises despite most of them relying on poor science.
I think there's newer news that AKG, an easy to get and cheap supplement, has anti-aging effects with no known issues.
https://www.science.org/content/article/bodybuilding-supplem...