As an effective altruist, I like to analyze how altruistic cause areas fare on three different axes: importance, tractability and neglectedness. The arguments you gave for the importance of aging are compelling to me (at least from a short-term, human-focused perspective). I'm less convinced that anti-aging efforts are worth it according to the other axes, and I'll explain some of my reasons here.

The evidence is promising that in the next 5-10 years, we will start seeing robust evidence that aging can be therapeutically slowed or reversed in humans.
[...]
In the lab, we have demonstrated that various anti-aging approaches can extend healthy lifespan in many model organisms including yeast, worms, fish, flies, mice and rats. Life extension of model organisms using anti-aging approaches ranges from 30% to 1000%: 

When looking at the graph you present, a clear trend emerges: the more complex and larger the organism, the less progress we have made on slowing aging for that organism. Given that humans are much more complex and larger than the model organisms you presented, I'd caution against extrapolating lab results to them.

I once heard from a cancer researcher that we had, for all ... (read more)

This was great. 

Some things that made it great:

1. It was just in the sweet spot of length. Taking notes, this took me a half hour to read. (I think the ideal is in the 30 minutes to 60 minute range, so doubling the post would have been fine, but more than that would have been overwhelming).
2. It was written clearly. 
3. It was full of links that I can use to follow up on the places that I am most interested / confused about.

I would love to read more posts like this one, on a whole variety of topics, and would be glad to help subsidize their production if there was a way to organize that.

I want to consider this post from a decision-making perspective. How can it inform my own future decisions?

First of all, this is the applied goal underlying my graduate-level research. As I continue to learn more about my field of tissue engineering, bioprinting, and regenerative medicine, I might be able to contribute to this growing anti-aging movement. So this post can inform my reading and writing decisions.

Without meaning to be rude, I'm not certain that these sources or this post is credible, simply because I'm only starting to read it and understand it myself. This question is due to my own lack of knowledge, not any issue with the OP. However, it might make a good starting point. It might be valuable to look at the sheer amount of reading it would entail, and the level of mastery I'd like to attain in this domain.

If I wanted to commit a total of 50 hours studying this body of literature, is this post the best place to start? If not, what is? I don't have any better ideas. Perhaps the key question is really where to start within this post.

I think I'm having these credibility and "where to start" concerns because this is a blog post by an anonymous author on LessWrong, rather... (read more)

I'm preparing for graduate school in tissue engineering via bioprinting. I was motivated by these considerations.

My sense is that ageing is both an evolutionary response to cancer and an entropic inevitability. No matter how much you supplement the body, eventually deleterious mutations will accumulate. The complexity of cellular systems makes them very difficult to improve on.

The strategy I envision is that we'll learn how to manufacture healthy, fresh tissues and organs from the recipient's own cells. While it's very hard to improve on the cell's natural mechanisms, we can harness it in this way to rejuvenate at the level of tissues and organs. People will receive periodic transplants of fresh organs built from their own cells.

It would be great if the mouse results turn out to apply to humans as well, but I have my doubts.  These doubts are based on what I thought were pretty conventional biological assumptions, but that nevertheless don't seem to be addressed in the anti-aging discussions I've seen.

The basic problem is that there's a good reason mice don't live long. Even if they didn't age, the environment in which they live means they are very likely to die in a few years from starvation or predation.  So genes that keep them from aging won't be selected for because of either or both of two reasons:  (1) The selective advantage of not aging, when you're likely to die young anyway, isn't enough to overcome random mutation that undoes the anti-aging genes. (2) The advantage of not aging comes at some (possibly rather small) cost in terms of increased likelihood of death from predation or starvation, or decreased fecundity early in life. (For instance, it might have an energy/food cost, or might come with decreased physical performance, such as in running speed.)

Humans live in a different environment, in which slower aging is more advantageous. And indeed humans age much slower than mice, ... (read more)

Random question: Why is there such a large difference between the life extension results for mice vs. for rats. Naively, they seem like they're pretty similar. 

Are we trying different kinds of treatments on one than the other for some reason, or is it just much harder to intervene on rat life-spans?

[F]ew members of [LessWrong] seem to be aware of the current state of the anti-aging field, and how close we are to developing effective anti-aging therapies. As a result, there is a much greater (and in my opinion, irrational) overemphasis on the Plan B of cryonics for life extension, rather than Plan A of solving aging. Both are important, but the latter is under-emphasised despite being a potentially more feasible strategy for life extension given the potentially high probability that cryonics will not work.

I think there is a good reason for there be... (read more)

Regarding cryonics not working: this depends on your definition of 'working'.  Let me describe the problem succinctly.

Assume at some future date you can build a 'brain box'.  This is a machine, using some combination of hardware and dedicated circuitry, that is capable of modeling any human brain that nature could build.  It likely does this by simulating each synapse as a floating voltage, modulated by various coefficients (floating point weights) when an incoming pulse arrives.  

Well, you can choose randomly the weights, and assuming ... (read more)

Promoted to curated: I've been meaning to follow up on the state of anti-aging work for a while, and this was really a quite good overview. I also know of a number of other people who found it useful. Thank you for your work when compiling this overview!

For personal longevity strategies, I recommend talks by Dr Rhonda Patrick, Dave Asprey and Dr Peter Attia. 

Dave Asprey is a person who claimed to increase their IQ by 40 points without engaging in any effort to measuring his IQ by taking the best results found in p-hacked trials for interventions and adding them up. I think that was even before he went into business as a supplement salesman.  

More recently he argued that he believes in reincarnation because it helps him to lower his stress levels. 

He references a lot of research, but I don't... (read more)

Hi, I was a talk at a conference, in 2019, that mentioned that many new breakthroughs in cancer research were down to improvements in the accessibility of data science, and large scale computing.

As a Software Engineer, is there any way I can contribute these type of skills towards longevity research? The only avenue I could find was to get a job at Calico, but realistically, I'm half a world away in Ireland.

Love this article.

After reading the The Fable of the Dragon-Tyrant a few years ago after my father died, I went into a deep dive on this and ended up making a calculator, comparing the impact of eliminating various causes of death on average / median lifespan. It's very simplistic, but I found it interesting to use to illustrate how ageing contributes to death:

http://life.analogmantra.com/ 

Thanks for an amazing post, Jack!

I think it's worth mentioning that damage accumulation as the root cause is not the consensus view anymore.

To quote Josh Mitteldorf, there are three views:

1. (from the “programmed” school) Aging is programmed via epigenetics. The body downregulates repair mechanisms as we get older, while upregulating apoptosis and inflammation to such an extent that they are causes of significant damage.
2. (from the “damage” school) The body accumulates damage as we get older. The body tries to rescue itself from the damage by upregulating repai

There is a problem with most anti-aging interventions: long expected duration of human trials, as results and lack of side effects will be obvious only decades after the start oа such trials. Without trials, FDA will never approve such therapies. 

However, there is a way to increase the speed of trials using biomarkers of aging - or testing of already known to be safe interventions, like vitamin D. But biomarkers need to be calibrated and safe interventions provide only small effects on aging. Thus, it looks like some way to accelerate trials is needed if we want radical solution to aging to 2030. What could it be?

Minor correction: the metformin trial study (TAME) is not currently underway; they are still waiting for the FDA to designate aging as an "indication" to be treated (and also raising funding).

Good writeup, though, thanks!

Besides donating money to SENS, is there any way for people with money to help speed up this research? Specifically, are there companies that one can invest in to help this research? Say if you're in charge of a lot of investment money (maybe you're a fund manager or ethical investment advisor or something) and want to make investments that make the world a better place. Anti-aging sounds like it would be a great place to invest some of the financial capital available. How would one do that? 

In part 1 is this error:

"This equates to 37 million people - a population the size of Canada - dying per day of aging."

Fix: change "day" to "year"

Do we understand why cats live longer than dogs?

I may argue against the anti aging field (and probably now that i reflect about it, it seems more important than most non-essential productivity in society) that it is highly more probable that we reach an agi singularity during our lifetimes, before we die of aging. (depends on your age). 
What do you think?

Science fiction author and physicist David Brin has pointed out a theoretical reason why we might expect anti-aging therapies that work in mice to fail in humans: the human lifespan is already a ridiculous outlier. Life spans vary with size, metabolism, and other factors, but one thing tends to hold constant: most mammals have a lifetime of about one billion heartbeats. Humans get a whopping 2.5 times that. An intervention would have to more than double a mouse's lifespan just to catch up with whatever it is that evolution has already done to humans - if there are any simple mechanisms that can cause a mammal's body to increase its lifespan, humans are probably already pushing them to their limits.

Fellow humans, do forgive my newbieness, but I am surprised this following study has not been mentioned: 
 - https://www.aging-us.com/article/202188/text
I speak no chemics, so I might've lost something midway of the presentation. Yet, since I have celebrated the aforementioned article as my most cherished 2020 article, I've guessed the chance of it cherishing someone's day upward was worthy of the hereby mentioning. I shall read replies probably: in case I take time to do so, one may consider oneself thanked for the reply, in advance.

I purely enjoyed the read about the State of the Art. I had no clue there's so much going on behind the scenes. 

If I may, I would like to steer the discussion from technology towards ethical and practical matters. 

The argument could go like this:

We're living on the cusp of technological progress. We (most western countries) enjoy easy access to more resources than we could ever consume and enjoy. The accessibility of the internet means we can communicate globally. We have cars and fridges and smart homes and Nicolas Cage pillowcases.  Y... (read more)

When it comes to the idea of massively improving healthcare outcomes there seem to be two strategies. One is to focus on antiaging. The other is to focus on increasing our research capability by improving the tools we have available.

When Zuckerberg went out and interviewed heatlh care experts it seems they convinced him that tool building is more promising then object level research. 

How strongly do you believe object level research on antiaging to be better then tool building? What's your argument for it?

I'm in support of anti-aging research, and think we should fund it more highly, specifically because the long-term benefits are so high once we get it right. Does anyone have any comments on whether SENS is the best place to put money if you're interested in donating to anti-aging? 

As a side note, my experience working with complex codebases has led me to disbelieve your optimism for how quickly we can find reliable ways to get more than a decade of increased healthspan. The human body is vastly, vastly, vastly more complex than nearly any codebase hu... (read more)

Is there any way for a small private investor to invest in this? By amount of risk, this is probably more of a charity than an investment, but with a small chance of hitting a jackpot.

Maybe some fund which invests into longevity projects? I could not find individual companies, which would be publicly traded.

On "Call to Action" : 
Besides sharing, learning and donation, why don't you encourage research-minded people to actually participate in / join the research? 

First, students or young researchers in position to choose or change their research direction.

Second, others: since the audience that will fully read such an article is likely to have useful research skills (biology, science, computer science etc ). Some may be willing to volunteer with their skills and join some project.

Thank you for the great article!
One possible minor correction: turtles do senesce https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988574/

Without aging, COVID-19 would not be a global pandemic, since the death rate in individuals below 30 years old is extremely low.

A pandemic is an epidemic that occurs across multiple continents. Note that we can accordingly envision a pandemic with a death rate of zero, but a pandemic none-the-less. Accordingly, I think you've somewhat overstated the punchline about aging and COVID-19, though I agree with the broader point that if aging were effectively halted at 30, the death rates would be much, much lower.

"Recently, a group of Russian biohackers recently performed..."

Just reporting a little mistake here.

Good overview.

Regarding parabiosis, are you familiar with the Conboy's research on diluted blood plasma? I know they are trying to get a trial going -- but suspect the effort has been a bit delayed due on the main event for 2020.

The evidence is promising that in the next 5-10 years, we will start seeing robust evidence that aging can be therapeutically slowed or reversed in humans

Are you willing to bet on this? If so, how much?

A very long article about anti-aging and not a single mention of the effect of insulin and carbohydrates on ageing. No mention of the use of a ketogenic diet as an anti-ageing strategy. 

At least you mentioned Metformin... 

It seems to me that unlike say, GAI research very little attention has been paid to the consequences of such work. I do not see how this would not result in a tiered society where at least at first those with access to longevity will be the wealthy and resourceful and thus able to tyrannise those that dont.

There are then of course a myriad of psychological/existential implications which someone like Scott Alexander would have a field day with. How can we give our time meaning if we have an unlimited amount of it? What about personal relationships? Or voca... (read more)