A primer on the current state of longevity research | Hacker News Reader

A primer on the current state of longevity research

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179 pointsabhishaike124 comments

Thanks for the review.

Surprised not to see any mention of interleukins and metformin. [Warning - metformin linked to birth defects]

https://www.nature.com/articles/s41586-024-07701-9

The more I learn about molecular biology/oncology, the more skeptical I am of longevity research. The pathways are usually broad hub genes that shouldn't be touched. E.g. Myc is an oncogene. As a rule of thumb, any time you see "reprogramming," be skeptical.

Gene therapy for neurodegenerative diseases should not be considered longevity.

thanks for reading!

i could’ve covered the metabolic/immune stuff in deeper depth…might make a part two for this all, i was pretty opinionated on what to add in, there is a lot more to the field

Life extension in humans is difficult because we are already long lived for a high metabolism large mammal. That means evolution has probably already tweaked the obvious knobs.

It doesn’t mean it can’t be done, just that it is not likely to be as easy as pushing a few chemical buttons or turning something on or off.

Why would evolution "tweak the obvious knobs" for something well beyond our breeding age 100-500-5000 years ago?

The best argument is that those same tweaks affect child bearing/survival performance in the same direction. Since sickle cell and other diseases were selected for, it seems unlikely all of them go the same way.

This. If anything, evolution would seem to select for lower longevity so more breeding sooner (assuming that if we live longer we would put off breeding until later, which may not be true, and if it is, is probably only true with contraception).

And, of course, the oft-repeated "anything that happens after reproduction is irrelevant to evolution". Which isn't 100% true (it takes a village to raise a child, after all).

For humans I can speculate generational knowledge is much more valuable since we can communicate using language.

Yeah, this, paired with a social scorekeeping system that literally kills old people if they are less useful (lonelier -> general health problems)

Grandparents contribute to the survival of their grandchildren. Evolution has selected for long lived grandparents. The same thing happened in elephants and whales.

This is my favourite bit of research regarding the grandmother effect - linking pathogen evasion to neuroprotective activities in old age, all at the molecular level, in an evolutionary context.

https://pubmed.ncbi.nlm.nih.gov/35809046/

True in the sense that evolution does select for populations with grandparents, but not entirely obvious in the sense that it is optimising the long lifetime of those grandparents. You don't need a lot of grandparents lying around in the community evolutionary speaking, they take resources to maintain. And there might be a limit to how long knowledge is useful for that evolution has sniffed out and calibrated lifespans to.

Human life seems to go through 3-4 phases (roughly youth, middle age and old age). The role of each of those is distinct and fairly clear, but it isn't easy to pick why evolution settled on specific numbers of years.

GP used to live within their family, caring of kids and helping with vegetable garden.

Their modern “living” in hospices, hospitals, far away neighborhood or vacation resorts have a minor effect on survival on their grand children. Probably negative effect for some pension systems.

By the age we currently stop being 'useful' as members of clan human, i.e. retirement, our forefathers in an evolutionary sense could already have been (great) great grandfathers. Our life as a pensionado or geriatric patient is already a form of life extension, an extra age compared to the stages we used to go through.

Evolution doesn't mean only what is useful stays, it is only when selected for under evolutionary pressure that things are forced to go a certain way, and only after many generations.

The uselessness of old age will only affect evolution if A) there will be a society that is mad enough to really 'do something about it' and B) such a society will eventually outcompete other ways of life and its values start to dominate.

I can imagine a politics where money spend on welfare and healthcare for elderly is minimized to such an extent that life expectancy starts dropping significantly. In a way, the US has something like such a 'make money or die' politics and indeed, life expectancy there is quite a bit lower than would you would expect from such as prosperous nation. Can be economically effective. But it competes which economies where people are productive at an older age, being more focused on staying healthy and significantly less stressed.

Yes our modern world does not make good use of grandparents. Given enough time you might expect that the cost of carrying elderly relatives is enough to select for quick dying grandparents. It might also select for healthy long lived grandparents who are not a burden. Probably both will be selected for in parallel .

> our modern world does not make good use of grandparents

Senior citizens today probably have more power (and productivity) than they ever have.

Distracting grandkids with stories, or showing them how to do things is a superpower.

Grandparents used to be younger, too. Women used to have kids before 20, often at 15. You could be a grandparent at 30.

But even old and infirm, still stories could be told, and caring for grandma was distracting for kids too.

There were a lot more kids too. Most women gave birth yearly, and yes more died, but there were still more.

Keeping those kids busy was a plus. Training them vital.

The cost doesn’t affect the survival of the descendants though. It has to to affect the gene pool.

When we're talking about evolution (of something like a human, not a bacterium or fruit fly) you can basically ignore anything that's happened in the last 25,000 years as an irrelevant blink-of-the-eye, timescale-wise.

Last 100 years? Forget it.

The speed of evolution is faster than you think. The reason for that is that mammals rely on sexual selection instead of random mutations. This means that the prevalence of a gene within a population can rapidly change from say 1% of the population to 60% of the population within a few generations.

Evolution can trivially happen within one generation. Just consider lactose tolerance. If it happens that the only source of food is milk for a substantial period, then anybody with lactose intolerance dies and the relevant genes can go from being rare to being 100% in the population.

I don’t know the vaccine evolution came very quickly and we arrived at DNA and RNA modification levels which are able to shape our further evolution for ever.

What are you basing this assessment on?

https://en.m.wikipedia.org/wiki/Grandmother_hypothesis

What do you mean by "breeding age"? Women of course undergo menopause at some point. Men may have peak vigour around age 40, but can continue reproducing into their sixties or beyond. In modern forager populations in Africa and Australia, it's common for men to take wives at such an advanced age.

See eg https://d1wqtxts1xzle7.cloudfront.net/46398103/s12110-000-10... . I don't know about the overall hypothesis, but there's some fascinating data there about how old men can get whole still playing important tribal roles.

Hmm, that link isn't working. Anyone interested should be able to access it by clicking the "PDF" link in the top right of Google scholar: https://scholar.google.com/scholar_lookup?title=The+patriarc...

Why is a good question, but if you draw a log-log plot of lifespan against mass for mammals, humans appear above the main curve. "That's unlikely by my model" doesn't change that.

I have long suspected that part of the solution to getting old will be delaying puberty. And in a world where there is more to know every year, that might not be such a bad thing for puberty to hit at 16 instead of 12-14.

But 16 year olds think they will live forever, so I’m not sure how that would work.

from an evolutionary perspective the current human lifespan seems almost perfect

>long enough for grandparents to help with kids and pass on valuable knowledge

>short enough that new generations are able to adapt as needed to changing environments and throw out out of date information or cultural "technology" that is no longer relevant

increasing human lifespan significantly seems like a nightmare, especially if only the richest have access. The saying "science advances one death at a time" and just the thought of political leaders being able to entrench themselves over longer times spans is awful. Seems like it would most likely lead to complete stagnation

The doses of metformin taken are really quite high (1 gram/day, say). It's mostly excreted in feces; the dry mass of which might end up ~1% metformin. It's one of the most commonly detected drugs in waterways. It biodegrades, but slowly.

You don't necesarily need gene therapy to "turn off" genes. You can just (temporarily) silence genes. Here's a podcast episode about just that (with the example of prion disease immunity): https://traffic.libsyn.com/secure/twiv/TWiV1127.mp3?dest-id=...

Also a fun related fact that I remember from Kurtzgesagt: whales should get tons of cancer (for being so huge), but they (almost?) never do.

I'm convinced that there are feasible ways.

They figure out how to prevent cancer, but it makes you huge and your limbs turn into flippers.

A cure for cancer and a return to the oceans? My friend, this is a feature not a bug.

all drugs "temporarily silence genes" by acting on the gene's target protein until the dose degrades.

silencing typically refers to siRNA/RNAi. There are only 7 siRNA approved, all for liver diseases

The craziest conclusion I've seen longevity experts narrow in on is the mTOR == cancer hypothesis. And the logic leaps are astounding:

1. Rapamycin inhibits expression of mTOR. (verified)

2. Rapamycin extends lifespan of cancer-encoded laboratory rats. (verified)

3. Therefore, activation of mTOR causes cancer. (???)

4. Therefore, stop eating protein.

The leap from 2 to 3 is incredible. These guys aren't considering the possibility that Rapamycin might have other cancer-inhibiting properties via other pathways. They're just assuming that because the R in mTOR stands for Rapamycin, that's the only thing the drug does.

I doubt step #1. When you downregulate mTOR, there are other supervisors of that pathway that help right the ship by upregulating it.

It's naive to think "we can shut off one of the most critical pathways in biology"

Can you share more on "metformin linked to birth defects" - my wife is on it, and she's a pharmacist - she claims this has not been proven so far

Was curious as well. The only thing I’ve found is a study on men taking metformin suggesting a risk of sperm formation that could cause defects in male offspring.

Longevity research is likely to improve quality of life too. Diseases that have been tackled separately since forever -- cancer, Alzheimer's, diabetes -- are starting to be seen as manifestations of a single underlying process, which is what we aim to stop.

> are starting to be seen as manifestations of a single underlying process

Eating and breathing pollutants ?

I'm not an expert in any of this, but from reading this stuff a long time it almost always goes back to inflammation.

Inflammation is still a symptom- body reacting to something that it doesn’t like so it’s like saying that almost every smoke goes back to fire. Not wrong, not horribly useful.

No that isn't it. Else all animals would have at least similar life spans. A dog doesn't die at 8 from cancer because of eating and breathing pollutants. And neither does a human at 80. The only thing most pollutants do is make it worse.

The underlying cause is our body not being able to maintain itself over even short timescales, with or without pollutants.

All animals have different responses to toxins, pollutants, cancer growth, etc. We're kind of actually at a "sweet spot" for cancer rates, big enough to get a lot of cancer, not so big that we need extraordinary cancer resistance like whales.

That doesn't make sense, if pollution was literally slowly killing us, and the planet, surely we would take some action to decrease pollution, and yet for my entire lifetime we've exuberantly increased it, recently going so far as to build bitcoin, a popular competition to pollute as much as possible in exchange for prizes.

Weirdly, if I do any amount of research, it does seem like there's strong correlations between pollution and most kinds of cancer, what a wild coincidence.

But the pollution in regard to bitcoin is CO2 from energy use. So this is an incredibly broad statement where you leap from cancer to climate change. "Killing us, and the planet"? Human activity in general causes trouble, that's your insight. We should take some action to curtail action?

There already are pollution controls. Stronger pollution controls might be beneficial, sure, but is that the key to longevity? Or is the connection here that you regard longevity as similar to pollution?

Something like 45 % of BTC energy consumption comes from coal, a rather impressive carcinogen.

I doubt it. In the book Outlive, they show the overall rates of mortality after subtracting for the 8 leading infectious diseases, and the death rate is mostly flat over the last 70 or so years. His conclusion was that neither environmental factors nor medical research has made much progress on things like cancer, etc.

Historically, the population of the world was exposed to much higher doses of common pollutants than today in much of the world. One example, see link below. If what your second line describes were so directly the case, then, for example, the people of late medieval Europe or the time of the early industrial revolution would have been saturated with diseases like cancer, alzheimers, diabetes etc. Maybe they were, since medical records from those times are barely above non-existent, never mind being clinically accurate, but the evidence either way definitely shows how much higher accumulations of common toxins were in people's bones, hair, blood etc prior to modern times.

https://link.springer.com/article/10.1007/s00204-012-0866-7

One mayor thing which changed definitely and is underrepresented is the exposure to various frequencies.

frequencies in what sense? The entire spectrum of communications frequencies used by our comms technologies, including 5G, are well inside the non-ionizing side of the EM spectrum. There's no evidence of them causing cellular harm, much less the kinds of shitty, long-term crippling or deadly effects that we clinically know are caused by the chemicals and elements humans have spent centuries casually contaminating themselves with.

Don't know the average age of partipants here but I assume it is low enough to explain the focus on longevity rather then on the quality of life.

If you get a chance to interview a person in their late 80s, ask if they would welcome a life extension of say, 20 years.

I've known two people to reach their 90s, and they were/are both happy for it. But one was very physically active, and one is wealthy enough to afford round-the-clock in-home care. I imagine for the middle class and infirm, reaching your 90s could be hell.

My maternal grandparents are in their mid to late 90s and it's indeed not glamorous.

Fortunately they've retained mobility, partly thanks to living four floors up without an elevator for 75+ years. As a side note in their block people passed away starting with those who lived closer to the ground.

Not everyone is this fortunate though, as grandpa's older sister is 100 and bedridden.

What you're describing has been known since the ancient Greeks made stories about Tithonus.

The reality is, current research mainly exists as "old age illness is expensive, can we prevent all those things going wrong by slowing down aging?" (Currently: yes, with multiple different approaches, but so far only in lab animals).

The Greek mythology is deeply plugged into the human condition. I didn't know the Tithonus story, my comment comes from personal experience.

Your personal experience of aging, or your personal experience of everyone ignoring aging? Because either way I don't see how what you wrote works.

We all experience aging, we don't ignore it, we literally feel it in our bones. It's the fountain of youth that's sought, with Tithonus being the "careful what you wish for" example to show the difference, precisely because we all know his end is not what we're seeking.

Surprised there is no mention of Bryan Johnson. Whatever you think of his methods, he has certainly done a lot to popularize longevity research in the last couple years.

Also no mention of rapamycin and related research on immune modulating pathways.

sure but he hasn’t contributed much to the actual research itself, i agree that he’s done cultural contributions, but afaict he isn’t funding much

rapamycin is something i left out yeah, just was something i was less interested in + believe in less. i really only covered sirtuins because its had such a large cultural impact through David Sinclair’s book on aging

What drives your skepticism of rapamycin for anti-aging?

> he hasn't contributed much to the actual research itself

From what I've read, he's done quite a bit of this but it's been restricted to a population of one. If his healthspan hits 120, the experiment he's run has been successful, no? He's already 46 so we will have a result relatively soon (within 60-70 years).

In 20 or 30 years you can look and see if he's 99th percentile for his age along whatever metrics (mile run time, VO2 max, skin elasticity, etc.) and that will be an obvious sign of a successful experiment.

Statistically it will not be a very useful scientific experiment - too many variables, too small sample size. Plus he will die a lot sooner from all the pills he is taking.

IMHO, even experiments that don't seem useful today can still be interesting.

Dying at age 48, 80, or 150 are all potentially interesting results.

I really doubt he will die young, people who die in their 40s usually have something they don't notice until it is too late (heart disease, cancer). There is no way he would not notice something like that lol.

The amount of testing he undergoes is as interesting as the regimen itself to me. So many things that take you out are very survivable if caught in advance, and he is going to catch everything.

Results on those timescales are a bit too much of a Pascal's Wager for my liking.

How do you get longevity results on short timescales?

GM lab rats if you want in-vivo, better computational models of you want in-silico.

Both are happening; I have no idea what ultimate (or indeed present) limits each has.

Rat experiments would give you longevity results for rats which may or may not be the same in humans. AFAIK, the only way to get actual results for humans is to run the experiment.

After seeing some of his daily routines I am not so sure he is that interesting to talk about. Lots of pseudoscience devices, I imagine his caloric restriction has been the biggest impact.

Yeah, a lot of his approach also seems to be to try everything that could remotely have the possibility of working, and if it works it works, if it doesn't he can afford the expensive pee and the time wasted.

For most everyone else that has to budget (both money and time) and try to figure out what core supplements and practices could be beneficial, that doesn't really help.

Caloric restriction thing is true, but is also what he advocates. He always says if you are not sleeping well or eating right don't worry about anything else. Red light therapy, supplements, stem cells and all the other expensive experiments he does are all less effective and shouldn't even be considered until your sleep, exercise and diet are good.

I am not jumping into his program, but I am definitely keeping an eye on him. If he is still doing the same protocol and he looks the same 10 years from now it will get difficult to keep criticizing it.

lol, bro takes 100 pills a day. With all the tainted supplements in the world, he’s just playing Russian roulette with pills.

It is hard to cover everything related to longevity, given that there is a vast diversity of approaches, and a lot of work presently taking place.

https://www.agingbiotech.info shows how much work goes into just making lists for just the industry side of the house.

Read a few of the lengthy end of year posts at Fight Aging! to see just how much there is to comment on (e.g. https://www.fightaging.org/archives/2023/12/a-look-back-at-2... ), and Fight Aging! only covers an opinionated selection of the full spectrum of research and development.

Should diet / exercise be the primary mechanisms to support longevity?

https://gero.usc.edu/2022/04/28/valter-longo-longevity-diet/

edit: also this is quite interesting https://www.bbc.co.uk/programmes/b01lxyzc

Life is too short to spend time reading a essay that could have been condensed to:

Nothing solid. Work in progress.

99% of proper good science is "Nothing solid. Work in progress.", it doesn't make it any less valuable. I prefer this honest and clear communication a hundred-fold over what comes out of universities' PR departments.

For the general public yes. But for researchers, it's super useful to know.

I spent 2 years of my Ph.D. pursuing a dead-end research direction. If only someone would have told me, "yeah, we tried that and it didn't really work."

This is why socializing at conferences is useful. Researchers will admit over a beer to stuff they tried but didn't work out and here's why.

Because academia never publishes negative results, you'll never find that out by reading papers.

That’s the tragedy of all research - very few negative results get published. For all I know most of the things I’m working on at the moment have been tried and discarded

So, I used to think this, but seeing a lot of success and failure in machine learning projects has taught me that negative results can be quite difficult to interpret. You typically don't know if it's because the underlying idea is flawed, something went wrong in the experiment setup, some bug went undetected in the code base, or whatever, we explored the wrong corner of the hyperparameter space, or whatever. It can also be the case that the idea is correct, but the effect is miniscule compared to other effects.

Now, when a pile of groups try something and it doesn't work out for anyone, things start getting interesting... But if course it takes pretty open discussion to know when that's happening.

There are, broadly speaking, two types of negative results. The most numerous one is when the researcher tried a thing but does not understand why the thing did not work. There are so many knobs that just from the plain combinatorial perspective these results are not very valuable - they carry next to no information unless someone else takes the effort to understand why the thing did not work. But there is another group of results, encountered quite often, where the researcher either knows why the thing did not work, or at least has a solid, plausible hypothesis. I wish this latter group was more socially acceptable to publish and valued by the community. It could still be that the person is "holding it wrong" even in this case, but still, it would be useful. The era when one could cheaply try something out because their training run completes overnight seems to be gone for good.

Yah, I think that's where the experience of how failure happens in machine learning projects is helpful. I've seen wrong explanations for root causes drag out for months and sometimes years, as we tried different attacks that just weren't working. ML experiments are often quite cheap, compared to things like clinical trials or field studies... So we can indulge in running another experiment to confirm or deny our hypothesis quite easily.

Humans are extremely good at inventing explanations for things. When the world doesn't do what we expect, we then have a choice of whether to believe we had the wrong explanation or just got the experimental details wrong... And epistemic hubris is a hell of a drug.

> Because academia never publishes negative results, you'll never find that out by reading papers.

And someone should be prosecuted for it.

Ah, compelled speech. So First Amendment. /s

The person you're replying to is not American.

On this issue, I feel sorry for them.

Thank you for your sympathy. Not being an American is one of my greatest sorrows.

Btw, I wasn’t entirely sincere in my comment above either. It was just a way to express strong dissatisfaction with the state of affairs.

transparency is good

So is brevity

I'm (somewhat) surprised to not see DeGray or his SENS mentioned in the article or the discussion. I thought he and his approach gradually moved from the area of crazy science to (at least) one of the approaches attracting attention from some more mainstream researchers?

After all the "Hallmarks of Aging" (2013), more or less mainstream research article published in "Cell", looked at the aging process from a similar perspective.

If I understand correctly, at least one of SENS components - namely, AmyloSENS - is currently being targeted by a number of biotech startups, looking into use of senolytic drugs to clear up senescent cells.

DeGray himself is currently attempting a Robust Mouse Rejuvenation however from what I understand the results from trial 1 were more than modest, if not to say disappointing.

Sounds like the future is bright for the field and that it has lots of applications. I'd imagine future aging treatments would employ several of these methods together, say cell reprogramming for your organs, along with resetting some of those aging biomarkers.

It's funny that it was considered a pseudoscience for such a long time, when there's lot of clinical applications outside of trying to live longer. For me, as someone with celiac disease, I know the age of my intestines are probably older than most people, after constant damage from gluten. It'd be nice to have a cell reprogramming treatment for intestines.

That would be nice, and for other things too, but wouldn't it theoretically be simpler to grow cloned organs and other body parts and surgically replace your old ones with those? (Obviously, there's real technological hurdles to growing cloned organs, but these seem somewhat easier than the hurdles for reprogramming your cells.)

Might be difficult for the brain, and a very significant amount of the elderly have brain problems (Alzheimer's and other forms of dementia)...

It seems difficult to replace bones, cartilage, muscles and skin.

How so? Surgeons do it all the time. You've heard of skin grafts, right? You can remove patches of skin and replace them with other patches of skin from the same person and it'll work fine, aside from scarring at the sutures of course. A common problem is not having enough skin to work with of course (it's not like people have lots of spare skin), but if someone got severe burns for instance and we could grow cloned skin for them to implant, that's far preferable to current techniques.

Of course, replacing anything has issues with 1) the trauma of surgery itself, and 2) scarring where things are cut and spliced, but this is better than not replacing things at all and just dying or getting an amputation or whatever. Of course, if you could just get an injection that programs your body to fix these things itself, that's better, but my whole point is that it seems to me that growing cloned organs is closer to our current technological capability.

I was thinking about it. It looks like sperm from PSCs is a thing[1] so might be ovums. That means you can clone yourself from yourself. It’s even more intense if the statement that stem cells start to combine themselves autonomously and make embryo is true.[2]

I’ve heard that it is possible to let grow one type of animal inside another’s animal womb is that true, any sources?

1. https://pubmed.ncbi.nlm.nih.gov/29717842/

2. https://www.technologyreview.com/2024/05/06/1092055/scientis...

> It's funny that it was considered a pseudoscience for such a long time, when there's lot of clinical applications outside of trying to live longer.

That's probably the reason why it's taken more seriously now (and not just by venture capitalists hoping to live forever): by now, all Western societies have population ageing problems. Due to better medicine, people live longer, but their actual productive lives are still comparatively short because of age-related diseases like dementia, increasing physical frailty etc. Plus, not enough children are born so the working population can sustain the elderly. So, even if the goal is not (yet) "living forever", societies are now more interested in at least tackling age-related diseases. Not sure if that will significantly increase life span, but it might still be an improvement.

Does anybody know of any longevity research on bacteria?

If we can put together Boeings and LLMs, we can probably put together computational models of longevity for living beings... even if it's just for Mycoplasma genitalium. But I have never heard of one.

What does longevity of an organism that reproduces by binary fission even mean?

What happens if you abort the binary fission? If the answer is "you shouldn't", please tell me why. My argument for why we should is that some people want to scientifically know if it is possible to artificially, arbitrarily extend the lifespan of an organism. What are the constraints? What are the possibilities? What is the cost? Can we use GPUs?

How completely nonresponsive to my question.

Boeing is a few orders of magnitude simpler than a single human cell. We can't even create a CFD model of an airplane that is realistic as can be seen on all airplanes or even race cars designed purely by CFD.

I don't know why but tech industry folks tend to be very resistant to the stupendous complexity of biological systems. The way biology builds functionality into structure can result in incredible space efficiency. Like neurons, for example. People assume the computational aspect of a neuron is only a tiny part of the structure of a neuron, when we have no reason to believe that. That is to say, people think you can equal its ability with a model many orders of magnitude less complex than a neuron. They don't want to think about the implications of that assumption being wrong.

I always find myself coming back to the dragonfly brain. A dragonfly brain needs exactly sixteen neurons to take input from the 30,000 ommatidia in its eyes, use that information to plot the three-dimensional flight path of airborne prey, compute an intercept course, and send those signals to the wing muscles.

How many transistors do we need for that? Input from 30,000 camera pixels, tracking moving objects in 3D space, computing vectors. Now you have a neuron to transistor efficiency ratio. Now multiply that by 86 billion. One brain. AGI's gonna take a hot minute, folks.

I don't know why, but certain people tend to be very resistant to the stupendous power of information systems. One such information system, the dragonfly brain, is amazing, and another such information system, the human brain, may never be sufficient to understand it... in the raw. But it is a proven fact that human brains can build tools and other information systems.

Take that DJI drone. For the sake of argument, let's assume it took 300 000 years to develop: that's for how long we know anatomically modern humans have been around. We could reduce it to 10000 years, to account only for modern estates and concentration of resources in such quality that people get time to do science, invent new things, and imprint all of that in the web of human culture (another information system). Anyhow, humans have developed a thing that flies and has a camera, and the two things are connected, in 300000 years. Insects evolved 2.6 billion years after life appeared on Earth. Is the DJI drone not as amazing as the dragonfly? And if not, but we keep making new versions of it for the next 1000 years, will it be able to catch up to the dragonfly?

Death by old age is mostly a problem of the multicellular living beings (where only a small fraction of their cells are converted into the cells of new young descendants), so it is not something that affects the majority of bacteria.

For most unicellular living beings there is no analog of death due to old age, even if their cells may be degraded by adverse environmental conditions, which can lead to the death of those cells before reproduction.

There are a few unicellular organisms that reproduce by an asymmetric division, in which case you could distinguish a "parent" and a "child". In such cases, the "parent" might be able to generate a finite number of "children", before being affected by some kind of senescence that sometimes may lead to death. Only for such unicellular organisms there may exist (or not) a relationship between their "longevity" and that of the multicellular living beings.

Another case of similarity to the aging of multicellular organisms is that for certain unicellular organisms that normally reproduce by simple division (mitosis) it is necessary from time to time to intercalate a syngamy-meiosis pair (i.e. a fusion of 2 cells followed by a division into 4 cells, to achieve the equivalent of a binary division of each of the original 2 cells). Without the intercalated syngamy-meiosis pair, such unicellular organisms seem not able to reproduce by simple division indefinitely. The state of such a cell that has passed through many simple divisions may be related to that of an old cell of a multicellular organism, or not.

Because multicellularity has appeared independently in many groups of living beings, even if most of them exhibit some kind of senescence there is no guarantee that it has the same causes.

Only for simple animals it is pretty certain that their aging mechanisms are related to those of humans.

Thanks!

> Death by old age is mostly a problem of the multicellular living beings (where only a small fraction of their cells are converted into the cells of new young descendants), so it is not something that affects the majority of bacteria.

Yes, and I know that there are multicellular organisms where senescence is pretty much a non-issue (hydra).

Senescence is two processes running in parallel: one is "bad luck" crippling the capabilities of a system. For example, a gene loses functionality after an error during replication. In general, it can happen that a subsystem strands in a part of its state space that it can not exit from, and this could happen even to single-cell organisms. The second process is a response to the first, and it is a set of evolved mechanisms that increases the fitness and/or average life-expectancy of an organism by preemptively shutting down the most fragile subsystems, the ones which are likely to fail early anyway.

Now, these are evolved systems, not designed. They work in an all-is-good-as-long-as-the-species-survives basis. And so comes the heretic question: what happens if the system is engineered? Can we develop and possess algorithms and workflows to design organisms with longer lifespans? Doing so for M. Genitalium is not going to do anything for humans, but once that ball is rolling, we may want to keep pushing the envelope and aiming for bigger and bigger model organisms, until we get to Canis familiaris. Then we pretty-promise to stop.

For now, we still do not have a complete understanding of any living cell.

The mycoplasmas have some of the simplest possible cells, so, as you suggest, they are good candidates for the first cells whose organization and functions will become completely known.

While it is unlikely that understanding a mycoplasma would provide direct information about the causes of senescence in any multicellular organism, there is no doubt that when either a mycoplasma or another of the simplest bacteria will become completely known, that will bring a huge jump in the knowledge about all living beings and from that moment on it will become much easier to discover the causes of senescence and how it might be prevented.

There are bacteria that have extraordinarily efficient mechanisms for DNA repair, so there is no doubt that it should be possible to improve the design of human cells to avoid the accumulation of genetic errors. However, this will not happen in a few years, but in at most a century from now it is very likely that this would be possible.

Nice review.

But I get the ick. As with AI/ML research, it has tremendous political, social, economic, environmental consequences. As AI/ML has shown, the pace of development and availability has outpaced humans' ability to think through the consequences until they have already happened and are in the hands of very powerful techbros and oligarchs. I have no appreciation of Hinton and other leaders' change of heart about the catastrophic consequences of their research.

A PhD in Longevity research, should be evaluated for its philosophical deliberations as much as it pokes the edge of the state of art.

Death is a tragedy. I see zero issue with longevity research.

Any second-order societal effects can be dealt with, but this is absolutely not an area where we need regulations and deliberation of "safety" when literally everyone you know, your children, and your loved ones will die without this research.

The problem of dying is a much more urgent problem than, say, overpopulation or duration of power. Those can be solved once we aren't all, well, dying.

Death is by design and is a vital part of evolution. I don't have issues with trying to make our human lives a bit longer (and preserving same quality of life), but achieving biological immortality would open a lot more problems.

This is getting close to negative eugenics. You might want to rethink your position.

This is just what life is... We can spend all day talking about fairy tales of living forever but this is reality lol. What position is there to rethink ?

Wrote the commentor on a sheet of glass and metal, sharing their thoughts at the speed of light over a planet-spanning communications network with thousands of nodes in low-Earth orbit, while others on that network acts as patrons to sponsor such research as "can we grow mouse fibroblasts in gatorade and other soft drinks as part of an ongoing project to build a meat robot?" (the answer, is this is surprisingly more viable than they expected).

It's very easy to be overconfident where the boundary is between fairy tales and engineering, the boundary between fairy tales and science is even harder, and even domain experts can get that wrong in both directions.

Not really some variant of eugenics. GP didn't identify any subset of humanity

That evolution be allowed to operate unencumbered by mitigation on human populations is literally a eugenic position. It's not necessary to identify specific genes or traits that evolution would act on for this to hold.

There are species that have negligiable sensesence, QED death isn't vital part of evolution.

But even if it was, why should we limit ourselves to evolution? Evolution did not design us to go to the moon, to split the atom, to have transplantable organs, to fly, to brush our teeth with fluorinated toothpaste, or to use contraceptives — it has only just managed to keep up with us wearing clothes and cooking our meals.

> Death is by design

This betrays a deep misunderstanding of the mechanics of evolution. Design is literally not even part of the equation. I suspect you actually know that, but may have let an emotional response confuse your position.

Radical ideas like "let's stop dying" often evoke powerful irrational responses from all sorts of people, but it's very important to stop and consider the source of that response.

For example, I'm envious of those who would live in an age of immortality (if it were to happen), as I don't expect such an outcome for myself, but I don't want to take that away from them if it's a real possibility.

> Death is a tragedy.

And so is life. One thing is sure, life is much better enjoyed when you don't spend the entirety of it trying to bend the rules and worrying about things you have no power over.

If you're not fit, exercising two hours per day, eating clean food at every single meal, skipping alcohol, living in a rural area far from pollutants, &c. you have no business discussing longevity in the first place imho. It's too easy to wait for the silver bullet complaining about how death is tragic while letting ourselves rotting away every second of every day

There's a lot of things people can do to improve life expectancy, but it is impossible for most people to move to the countryside because houses aren't mobile like that.

Even then, good as fitness is, it doesn't make us agesless. We can research aging without solving all the rest of the issues first — not even maximum life duration, as 81 years where your body clock never goes past 25 is still an improvement on 81 years where you slowly wind down from 25 onwards.

Also with the food, there are often efforts to get the population as a whole to eat healthier, these get pushback that calls it "nanny state" (in the UK) or just outright denies the health impacts of the food that's being advised against (I wonder, find a "end fat shaming" headline, go into details, will you find a maker of junk food sponsored the research?)

Weird take. It's actually totally normal to be shaken by death, regardless of how fit you are. I would imagine most people don't want to die.

> The problem of dying is a much more urgent problem than, say, overpopulation

How are you not connecting overpopulation and longevity? The earth is already straining, even with the current level of population and longevity. If no one is dying until they are 200, and increasingly consuming like the richer nations, we are going to be living miserable lives.

Perhaps the people who advocate for longevity should spend a year in any one of the third world's populated cities and experience it first-hand.

If we live to 25 and have 5 kids, population goes up.

If we live to 200 and have 1 kid, population goes down.

> and increasingly consuming like the richer nations, we are going to be living miserable lives.

Tautologically false; if the worst off are empowered to consume as we do now, those lives will be *amazing*.

Also, the sustainability level of consumption depends on tech, not population. If we wound back to 1930 tech and population, we were reliant on coal and oil, we couldn't substitute other things for them — if peak oil/coal had happened in that decade, we'd have been stuck; now we're good, coal is being phased out as fast as we can build the alternatives, and we have partial alternatives for oil and are working on the reminder.

Let's say longevity was already a solved problem and people had unlimited lifespans. Would you advocate executing everyone once they reach 85 so that we can avoid the problems you refer to? If the answer is no, then the only consistent position is that longevity research shouldn't be blocked. In both scenarios, the solution is to work on those additional problems rather than deliberately kill people.

Well, I don't want it to get to a point where it is already a solved problem.

Length of life should not be the criterion; quality of life should be. If every one lives to be 200, then the quality of life will necessarily reduce for everyone; we are already straining the planet's resources, even if we don't make strides in keeping everyone fit and independent until they die.

This hinges on the idea that death is preferable to a lowering of your current quality of life, which is very much not something that people are going to agree on.

There might be some parallels with petroleum extraction. It would have seemed impossible to ban / regulate drilling even if the global warming in 100 years had been obvious.

So many good things made and personal fortunes generated by oil extraction; preventing those benefits would've seemed immoral.

Life extension is kind of like that, it's easy to say "someone will deal with potential problems later". A person only looking out for themselves and an altruist can both present an argument based on morality.

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