In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’ (2019)

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.

[1] https://doi.org/10.1016/j.cmet.2020.08.004

Anti-aging effects in mice*

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.

That article says that AKG was 2% of those mice diet, that a lot of supplements if the dosage transpose linearly to humans!

Time to hit up my gymrat brother for some testosterone I guess!

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".

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.

I can the recommend recent interview with him on the The Knowledge Project podcast. Had a lot of aha-moments listening to that.

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.

Ask Dave Polumbo

GH by itself decreases insulin sensitivity, aggravates insulin resistance, and may significantly increase cancer risk.

It has to be refrigerated, which makes travel difficult. Not to mention the hypodermics needed for intramuscular injections.

You can significantly boost your growth hormone level by using nicotinic acid (Niacin) and exercise, have a look at figure 3 in this paper https://journals.physiology.org/doi/full/10.1152/japplphysio... .

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.

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.

If you have a large dog, you can sign up for a lifespan extension study now with rapamycin. https://dogagingproject.org/

I think daily exercise can get you #1 As for #2 Totally. We’ll only show that we deserve longer lifespans if we solve it first for dogs.

“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."

Similarly:

"Science progresses one funeral at a time".

https://en.m.wikipedia.org/wiki/Planck%27s_principle

Sounds like a self solving problem.

I reckon people will start caring about their despots if they expect to live a millennium under the despots' boot

"Give me liberty AND give me death"?

I'd prefer to solve the despot problem in a way that doesn't involve me getting dead.

Several countries have managed to not have despots for long periods.

Teens there were give mega doses of multiple anabolics steroids

Also hgh at a young age won't increase life span later in life anyways

HGH seems to increase insulin resistance so without other interventions (e.g. metformin) it may be pro-aging.

Exceptional athletes in general may not have the same lifespan as age-matched healthy counterparts so not a good population to look at.

By what basis do you make this estimation? The factors for aging and feeling awake arent exactly comparable.

The issue with metformin is your own personal gastrointestinal sensitivity to it. If you're tried it in the past and quit, people have reported success with the time-released variant. See https://www.drugs.com/pro/metformin-extended-release-tablets...

If money was what it took to be correct in medicine, Theranos would be a huge success.

This is a good question:

> 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?

> throwing an entire gas station into the fire?

Why? Longer span can also mean longer healthspan.

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]

[1] https://en.wikipedia.org/wiki/Population_decline

Depends on where the additional years are added. Around the middle of life or in its end.

dehydroepiandrosterone (DHEA)

DHEA, Metformin and HGH.

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].

[1] - https://www.youtube.com/watch?v=KukRAXnNOJM

Quite the opposite, I think?

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.

You might change your mind when you're older. And wealthier.

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

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

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.

Getting old is a nightmare. You must be very young if you don't understand that.

When the supply of something is unlimited, it's value tends to approach zero.

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.

One thing I rarely see mentioned in regards to living forever is that during a life you will accumulate mental scars.

My wife has lost a sister, and she's witnessed a murder. Neither she nor I are the same after those experiences. I don't think we will ever be.

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".

Maybe it's a "challenge" that will also be solved - with memory erasure or what not - but it seems like an overlooked issue to me.

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.

> Am I the only one who thinks immortality is a nightmare?

Who's talking about immortality anywhere? It would be already great if you could die in great shape, not stuck on a wheelchair for years.

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.

I can't help but feel there is an element of self-justification in that sort of view.

We can't stop death, therefore we tell ourselves its ok and something that we actually want, in order to cope with the terror of death.

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.

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?

Increasing functional span is compelling.

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 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.

I don't understand people who don't want to at least have the option. I mean, if it turns out you don't like living longer you could just opt out?

As far as I can tell, "I don't want to live forever anyway" is just cope.

You say this now. How will you feel as your body gradually breaks down, and you stare into the void?

Depends where you live.