Thread

Loss of cell identity drives human aging: Two new papers

369 points · 184 comments · bookofjoe

dyauspitr · 1790966547 · focus · HN ↗
So chronic stress is one of the main contributors to aging. I hope I make it to my 40s.
Do we currently have the ability to do targeted methylation or de methylation at sites in cells?
1. SlightlyLeftPad · 1790967259 · focus · HN ↗
  Good news! Research shows that hope reduces stress! [0]
  [0]: <a href="https://www.forbes.com/sites/tracybrower/2024/09/15/how-being-hopeful-reduces-stress/" rel="nofollow">https://www.forbes.com/sites/tracybrower/2024/09/15/how-bein...
  1. dyauspitr · 1790967974 · focus · HN ↗
    What about Xanax or medication. Hypothetically ignoring the ill effects of the drugs themselves will chemical stress relief have the same anti-aging benefits?
    nradov · 1790968450 · focus · HN ↗
    If you believe that HRV is inversely correlated with stress then Xanax has the opposite of your intended effect.
    Shitty-kitty · 1791009864 · focus · HN ↗
    They are not talking about stress in the "mental health" setting, rather the metabolic one.
    dyauspitr · 1791012333 · focus · HN ↗
    In most cases they are the same thing.
    Shitty-kitty · 1791017970 · focus · HN ↗
    Most of it is oxygen. Oxygen is highly reactive so the same thing that makes it a good as source of fuel, also makes it poisonous. It is a double-edged sword.
  2. amelius · 1790968161 · focus · HN ↗
    Sadly, AI just made many of us lose all hope.
    whatsdowndog · 1790974423 · focus · HN ↗
    You spelled SI wrong.
    tempestn · 1790976603 · focus · HN ↗
    It makes me concerned on many levels, but perhaps also more hopeful. It was inevitable that we would eventually develop AI if we didn't go extinct first, and while there are myriad risks and challenges, there is also massive potential, which seems like it could be a source of hope. As the earlier comment said, the only way that therapies like these could be remotely viable on any kind of near to medium timeframe would be with AI assistance, and this is just one example.
    missedthecue · 1790983058 · focus · HN ↗
    AI is an amazing Rorschach test in this regard. In the way that two people will look at it -- not just AI in general but in a specific implementation of it (coding, vidgen, etc). And one will feel deep dread and knots in their stomach while the other is filled to the brim with hope and optimism.
    I think the former group almost certainly outweighs the latter group at least in the Western hemisphere, but I know the Western hemisphere has been steeped in a deep malaise of anti-optimism for several decades preceding AI to begin with. That it's almost a game to identify all the ways anything new might be bad, rather than celebrating the obvious ways they are good. And this penchant invariably biases their developing opinions of all new technology, be it AI or anything else.
    leptons · 1790986011 · focus · HN ↗
    >one will feel deep dread and knots in their stomach while the other is filled to the brim with hope and optimism.
    Ignorance is bliss
    DennisP · 1790986301 · focus · HN ↗
    What if I'm super optimistic about most technology but also scared of AI?
    Space, nuclear fusion, advanced fission, the internet since about 1993, blockchain, anti-aging, I've been a big fan of all of it. But I've read the AI safety arguments and seen what a lot of researchers say about it, and I'm seriously worried.
    E-Reverance · 1791005305 · focus · HN ↗
    What AI if is the only means for having those in your lifetime
    DennisP · 1791030644 · focus · HN ↗
    Some of them already exist. I'm optimistic enough to think plain ol' humans can do the others. I'm also fine with narrow AI that doesn't present the same risk as ASI; Google has built such AIs for protein folding and nuclear fusion, and nobody worries that they'll be any sort of problem.
    If ASI is the only way then I'm fine with dying of old age without seeing this stuff, rather than risking human extinction. And even if ASI doesn't kill us, I'd rather see humans do it, instead of watching ASI do it while it keeps humans as pets.
    We've come a long way all on our own. I don't think we've run out of tricks. It would be a shame if the human era came to an end.
    sfn42 · 1791024681 · focus · HN ↗
    What are you worried about? All the worries seem like bullshit to me. Like we're not going to have some runaway skynet thing, that's just completely off the table. These things run on data centers, we can just turn off the data center if we need to. I don't really see that becoming necessary either but we could.
    And then there's fears that someone might use it to engineer a super virus or something like that, which isn't really a new worry. People could do that before too, but it turns out creating a global epidemic isn't really a thing very many people want to do, and it's harder than most people imagine.
    "AI" are just chatbots. They can't fabricate robots to take over the world, in fact they have very limited reach into the real world altogether. Sure maybe you could envision some kind of malicious hacking, sabotaging some industrial control system to create a disaster of some kind or whatever but that was a worry before AI too which is why most critical systems like this are air gapped and have safety mechanisms.
    So I really just don't understand how people think AI will destroy the world. And I think its especially frustrating to see all this energy going into AI-related despair when climate change actually is on the brink of actually destroying the world in a completely real and concrete way, but most people don't give a shit about that. Some people will say it's natural cycles or some other variant of denying the problem, others will say it's not a big deal, yet others will say science will solve it, we'll capture the carbon or spray aerosols into the atmosphere to stop the warming etc.
    And they're all wrong. It's not natural cycles - shocker, climate scientists know about natural cycles. It is a huge deal. We're at +1.5c now and it's already having huge compounding effects. Warming is accelerating, we'll likely be at +3c in just a few decades. That is already approaching apocalyptic levels of warming.
    Carbon capture is a joke, there is absolutely no way carbon capture solves climate change. We would need tens or hundreds of thousands of carbon capture facilities all over the globe, it would be the largest engineering project in history by orders of magnitude. There would be many times more capture facilities than power plants. Nevermind the energy, concrete, chemicals etc required to build and run all of them, not to mention actually deal with all that carbon they would be capturing. It's not feasible.
    Climate engineering would be highly experimental, and it would also be a gargantuan project requiring enormous economic investment. It would likely have huge unintended consequences, and it might not even work. It might also have different consequences for different nations creating huge political issues - what if a country does climate engineering that's good for them but disastrous for their neighbours? Is it even possible to do climate engineering in a way that isn't bad for someone? Is it even possible/feasible to do it on the scale necessary to actually combat global warming?
    Yeah I don't know why people are panicking about AI, if there's anything you should be panicking about it's global warming.
    DennisP · 1791031516 · focus · HN ↗
    I'm quite concerned about climate as well as our other horrific environmental problems, but there can be more than one giant existential risk at a time.
    I'm not concerned about today's AIs. But three years ago they couldn't add numbers accurately and now they're doing world-class mathematics. If it gets much smarter than us, then it will run the world economy, because anyone who doesn't use it to run things will be outcompeted by those who do. At that point we'll have lost control.
    sfn42 · 1791032552 · focus · HN ↗
    The way I see it we already have lost control. Hell, maybe we never had control in the first place. We've known about the effect of greenhouse gases for over a century and we still keep investing into fossil fuels. Because "economics".
    If we had control we would have looked at the situation and gone balls deep into nuclear and other green alternatives many decades ago.
    dahart · 1791037183 · focus · HN ↗
    Some people certainly have been diving into nuclear & green for decades, and we now have far more wind, solar, and hydro power than we did several decades ago. Nuclear has been flat for only 2 decades and is about to start growing.
    “We” certainly have had control the whole time, “we” have been consciously creating greenhouse gas emitting machines while knowing the consequences. It is the economics. The delay in environmental consequences combined with the immediate financial benefits of easy power & transportation made the choice too tempting for some.
    The kind of control you’re talking about is self-control. We’ve always had the option to stop our bad behavior, and we chose not to. And we still have the option to exercise self-control with AI. The question is whether that option might disappear soon. Can AI get good enough that we will actually lose the choice to regulate ourselves?
    ben_w · 1791036849 · focus · HN ↗
    > What are you worried about? All the worries seem like bullshit to me. Like we're not going to have some runaway skynet thing, that's just completely off the table. These things run on data centers, we can just turn off the data center if we need to. I don't really see that becoming necessary either but we could.
    We can't even turn off the coal plants when the owners specifically want to because it's not making money, in part because the President thinks Global Warming is a hoax: <a href="https://www.utilitydive.com/news/washington-earthjustice-sue-doe-centralia-emergency-order-transalta/813754/" rel="nofollow">https://www.utilitydive.com/news/washington-earthjustice-sue...
    Also, there's a whole bunch of companies pursuing space-based data centres, which I think are dumb for a lot of reasons, but not quite dumb enough to not be a threat in this kind of manner as a few thousand GPUs is entirely doable before anyone decides it's not value for money.
    Also, we demonstrably have useless-to-just-bad monitoring in place, which is how all the things on <a href="https://www.felonybench.com" rel="nofollow">https://www.felonybench.com happened. That the companies could have done better, and should have done better, does not change the reality that they in fact did not notice until after the events.
    Also, there's at least two companies putting these things in control of wet labs. Good news: they're currently too bad at this to pose a threat. Bad news: "currently" is doing the heavy lifting.
    Also, there's a lot of people who are blindly using agentic AI and not checking anything, despite all the advice and case studies about why this is a bad idea and to not do that.
    Also, there's a lot of people e.g. on Hacker News whose response to all the attempts to create guard rails on the AI's behaviour is to call this "censorship" or "a lobotomy"; and also a lot of people whose response to calls for regulation of the companies is that this is "regulatory capture". (Worse news: The US president has rejected calls to slow down AI, saying "whoever wins AI, wins").
    > And then there's fears that someone might use it to engineer a super virus or something like that, which isn't really a new worry. People could do that before too, but it turns out creating a global epidemic isn't really a thing very many people want to do, and it's harder than most people imagine.
    The number of people able to do so has likely gone up by a factor of 10x or so in the last decade. AI's ability to use tools on behalf of their users is a further amplifier on this, unless safeguards are in place. Bad news, "safeguards" is a pretty vague term, and vague platitudes are not enough.
    More worrying is the possibility that some idiot will set biology challenges similar to the cybersecurity challenges which led to HuggingFace, with similar lack of oversight, and the agents will do much the same thing but with DNA/RNA-on-demand services. I really hope their equipment is better secured than HuggingFace was.
    Good news: the agents in the HuggingFace incident did not act with what would be called destructive "intent" if a human did it. Bad news: they still did the things.
    > "AI" are just chatbots. They can't fabricate robots to take over the world, in fact they have very limited reach into the real world altogether.
    No, they're not "just" chatbots. They're also tool users that can see.
    Good news: yes, they can't fabricate robots. Bad news: Guess what Musk is trying to do. Good news: Musk's timelines are wildly overoptimistic.
    > Sure maybe you could envision some kind of malicious hacking, sabotaging some industrial control system to create a disaster of some kind or whatever but that was a worry before AI too which is why most critical systems like this are air gapped and have safety mechanisms.
    Bad news: We're really bad at properly air-gapping stuff. We only know about Stuxnet because it breached an air-gap. This kind of thing happens a lot, even for really important stuff.
    > So I really just don't understand how people think AI will destroy the world.
    Ultimately, all it needs for this is to do what it was told, instead of what was meant.
    All humans acting perfectly would prevent all the bad outcomes I can think of, but (1) that never happens, and (2) "that I can think of" is doing a lot of heavy lifting there.
    > Yeah I don't know why people are panicking about AI, if there's anything you should be panicking about it's global warming.
    People can care about more than one thing.
    Look, you're worried about climate change: AI appears to be quite effective at convincing people of stuff, just consider how bad it would be if all the people who get rich from greenhouse gas emissions outspend environmentalists on AI-driven PR/marketing.
    [deleted] · 1791068138 · focus · HN ↗
    [deleted]
    jodrellblank · 1791038313 · focus · HN ↗
    > "we can just turn off the data center if we need to"
    1. If it never happens or AGI is friendly then we won't need to. If a hostile AGI is created, one trained on all writing about war and strategy and deception, able to respond in microseconds, with has ample time to plot before it makes an obvious move, then thinking you will wait until you see it attack and then turn off a datacenter, is way too little, too late. Like saying "the nuclear bomb explosion is local to one place, if it hurts, we will just walk away from it".
    2. That claim does not hold water once you start to dig into who, specifically, would turn off which specific billion-dollar datacenter, under which conditions. Google has been moving compute jobs around the planet to get nighttime electricity rates for bulk compute jobs for years, the idea that there is "one datacenter" is far too simple. The idea that employee 74,123 at Meta doing AI research is also able to get a Meta datacenter shutdown quickly on request, or would know enough about Meta's infrastructure to know which datacenter, seems unlikely. The idea that it even has one off switch, or that nobody will quickly power it back on, or that the compute jobs will not pick up automatically somewhere else, or that nobody else on the planet will be at a similar point in their research, also seem important.
    3. This assumes there will be a simple critical point that makes it clear we need to "turn off datacenter now". The fact that you then go on to talk about climate change, imagine you had said "we can just turn the factories off if climate change becomes a problem" and maybe that will make it clearer. Who will turn which factories off, at what point in the climate catastrophe, and why haven't they? That's why it won't happen with datacenters either.
    > "Like we're not going to have some runaway skynet thing, that's just completely off the table."
    You're confident that tens of billions of dollars of investment and research, US v China national AI competition, some of the largest companies in the world researching AGI will be a flop and develop nothing? Despite the progress from GPT2 to present day, despite historic analogies like the Wright Brothers to the Moon Landing in one lifetime?
    NVidia shipped an estimated 40 million GPUs in 2025. Say they average 1 TFLOPS each and a year has 31 million seconds, that's 1.2 million million quadrillion calculations in a year. That much compute power piling up around the planet year-on-year is not going to be important or relevant to the near-medium term future? Because it's just "off the table" that anyone could invent anything interesting with that much growing compute in the next ten or twenty years?
    lofaszvanitt · 1791068014 · focus · HN ↗
    They get electricity through cables. You nick the cable, end of story for the datacenter. Dataceters in space, welll.... not a good idea. When AI systems gets hooked to humans via brain interfaces and human like robots, well we'd better start worrying.
    jodrellblank · 1791124427 · focus · HN ↗
    That doesn’t address any of the points I raised about who would make the decision, or about compute jobs moving to another data centre, or about a dangerous AI deceiving that it was stupid until it had a plan to account for that, or an AGI responding much faster than humans, but it raises new points - how do you “nick” a 20 MegaWatt power feed without dying, and what do you do about the batteries and generator backup in a secured area?
    Now are you imagining that the employee who can’t ask for a data centre to be shut down, can call the military and telling them a self-improving AGI is about to destroy the world and they need to attack an American company?
    lofaszvanitt · 1791195873 · focus · HN ↗
    People in need are usually creative in their ways...
    Morromist · 1791005597 · focus · HN ↗
    AI would be much easier to be optimistic about if it were in the hands of people I like and trust. Its in the hands of people who appear to be complete psychopaths instead.
    missedthecue · 1791010996 · focus · HN ↗
    On the other hand I'm amazed at how flat access is. Access to the best models available is incredibly inexpensive relative to technology in the past, and everyone in the world with at least a smartphone has access to an LLM of some sort now.
    Second, the technology is very open. It's not as if the ONLY way to access an LLM is to pay a toll to Sam Altman. Models that are very good can run on my Macbook for the price of electricity and they're only getting better.
    kakacik · 1791022434 · focus · HN ↗
    Sure if you work in anthropic / openai or several connected / similar places future is exciting. And that's about it for the list, over-represented on HN but not really out there in real world.
    Literally everybody else, all white collars including, feels they could be replaced in 5-10 years. Just talk to people ffs, its not that hard. Literally everybody is worried, doctors (know plenty from all parts of medical care), lawyers, bankers, tons of various bureaucrats, ALL are afraid in one way or another. Its also sort of helpless worry you have 0 control of, not very nice place to be 24/7 in the back of one's mind. Double that for parents with non-teen kids.
    I use nature to relax and recharge and it works wonders. But reality is as it is and I have 2 small kids, I don't expect to hold the job I have in next 5 years, maybe due to llms maybe not. But I will have big issues finding another job on over-saturated market at that point, thats completely on llms. Thus as any sane person, hating the tool destroying my/our future while using it from time to time (in minimal fashion, code churning is really not a bottleneck in any decently large company and certainly not mine but I can imagine code sweatshops doing various cruds and eshops all day can be much faster now).
    someonebaggy · 1791032268 · focus · HN ↗
    This is not without reason, since living standards have been steadily declining since 1971, and every new technology has been explored by the rich to ensure that living standards decline faster.
    ben_w · 1791034883 · focus · HN ↗
    > since living standards have been steadily declining since 1971
    There are living standards issues; one of the big ones is a map-is-not-the-territory problem: people treat "living standards" as if it's a single quantity.
    It's really a whole bunch of different things coming together, with different people caring more or less about different things: some of us tie the idea of "living standards" to overall GDP or income per capita; others to house prices, cost of medical care, can they afford to start a family, etc., none of these options are entirely right nor are any entirely wrong.
    For example:
    I'm now living in a house so well insulated that when we accidentally switched the heating off it took a week to notice even though it was snowing outside; the air is clean everywhere (except on new year's night when the fireworks are ridiculous); there are cures for an increasing number of previously untreatable diseases.
    When I was a kid, the wooden window frames would rot from the condensation in winter; the petrol contained lead, and indoor social areas permitted smoking; HIV was a death sentence.
    By many measures, my living standards are way up. And yet, no kids to share this all with.
    someonebaggy · 1791039085 · focus · HN ↗
    You can make rough comparisons though. I'm sure your house being 20 times more expensive more than makes up for it being well insulated.
    ben_w · 1791042349 · focus · HN ↗
    The ratio of wages to house prices did not change 20x, more like 1.6x. Though that will vary depending on where you live, of course, and also when your childhood was.
    And yes, I think that price gap can be justified entirely by the insulation, when I look at energy costs per square meter in old buildings, available to me thanks to European requirement for energy performance certification. And that's even before PV so cheap it pays for itself in a year, which I have on my driveway right now.
    The childhood home had single glazing, limited loft insulation, the cavity wall was just a cavity and had no insulation filling it, gas central heating. It was cold even with the heat on in winter.
    So, I effectively spent just as much overall as my parents did, wage adjusted, but I'm much warmer for it.
    Basically, I've gone from a childhood in a relatively big place that today would be considered "in need of modernisation" even at its best if it were listed for sale today, to a place which is about average size but of a quality far in excess of what anyone would have bothered to attempt for a normal family home when I was a kid, not even in a show home.
    (And this was the cheapest new build I could find).
    someonebaggy · 1791203434 · focus · HN ↗
    I saw 20x and even higher. Where did you get 1.6x?
    orangecat · 1791041047 · focus · HN ↗
    living standards have been steadily declining since 1971
    This is generally false, and in areas where it's arguably true the problem is usually terrible policies, e.g. forbidding people from building housing and then being shocked when homes are unaffordable. On the other hand technology has improved living standards substantially; in 1971 less than 20% of US households had a dishwasher and 30% had air conditioning.
    m0llusk · 1791073264 · focus · HN ↗
    Having been involved with development of Internet social media and smart phones it seems like balancing futurist hopes with guarded pessimism might be an enlightened path.
    tjwebbnorfolk · 1791040181 · focus · HN ↗
    That's your decision
  3. whh · 1790968523 · focus · HN ↗
    Sometimes I like to close my eyes and dream of electric sheep.
  4. closingreunion · 1790969371 · focus · HN ↗
    Thanks, Obama
2. Chance-Device · 1790971024 · focus · HN ↗
  > Do we currently have the ability to do targeted methylation or de methylation at sites in cells?
  No, and you probably wouldn’t want it if you could. You don’t know what mutations are lurking in the genes that have been switched off or the consequences of turning them back on.
  I’ve thought about this a bit, and what resetting the methylation map really requires, in addition to actually resetting that map, is resetting your genome to a known good state.
  That’s pretty radical, but to selectively switch methylation on and off with precision you’re already talking about science beyond anything we have, featuring custom engineered constellations of proteins that unwrap your chromatin from around histones and then walk along it changing methylation state, then pack everything back.
  And doing it for each cell type, without applying the wrong map anywhere.
  And knowing what all the cell types and their correct methylation maps actually are.
  And assuming that methylation isn’t used anywhere, for example in the brain, in a way we don’t expect.
  And methylation isn’t the only kind of epigenetic modification.
  So, if we’ve solved all of those problems, rebuilding your DNA to a clean, mutation free state at the same time should be a breeze.
  We really do need AI for this if any of it is going to be remotely feasible.
  1. shevy-java · 1790973182 · focus · HN ↗
    > We really do need AI for this if any of it is going to be remotely feasible.
    Would you give your life into the hands of AI skynet slop?
    I understand your rationale, of course, but I for one don't want big fat mega-corporations dictate over our life here. Naturally, all of this hinges whether AI can even solve this problem. I assume it can, but I doubt it can do so initially - and the legal implications are still enormous. I really am not ready to turn my hands to claude's gene therapy slop.
    Alive-in-2025 · 1791007085 · focus · HN ↗
    why do we need ai for this? Yes, it's hard, so is laying out millions of gates in a cpu, later billions. We did it with software, not necessarily ai.
    someonebaggy · 1791032205 · focus · HN ↗
    Useful things like AlphaFold are getting conflated with LLM slop machines under this single "AI" umbrella.
  2. yieldcrv · 1790973401 · focus · HN ↗
    in my futile searches for meaning I’ve wondered whether cancers in humans are a failsafe to something else or preventing something worse
    more specifically the lack of more failsafes seen in some other mammals are a reaction to something besides happenstance
    jhrmnn · 1790975932 · focus · HN ↗
    Cancer is the price we pay for complex multicellular life. It’s not a failsafe, it’s the failure of all failsafes to regulate cellular growth within an organism.
    yieldcrv · 1790985357 · focus · HN ↗
    Larger mammals with many more cells have additional protections against cancer
    Such as longer and more numerous telomeres
    Hence why the human situation stands out to me and can’t be reduced to “it just is“. Some other mammals have it worse though
    usrnm · 1791008902 · focus · HN ↗
    Evolution doesn't care about individual organisms, it's all about reproduction. Our lifespan is enough to raise a few children and pass genes on, so, from the evolutionary point of view, it's adequate
    yieldcrv · 1791010489 · focus · HN ↗
    I understand, I'm equally frustrated when people including scientists say that something evolved for an environmental specialization, instead of the evolution being happenstance that may have incentivized more viable mutant offspring surviving until reproduction in that environment, but was not "for" anything.
    and yes, so I understand that with human cancer, it tends to happen or advance after reproduction has already occurred so therefore those traits are not selected against. it's impossible to weed out with human mating strategies
    I would just like to believe the cancer itself is an adaptation preventing something worse, but you're right, it doesn't work with the natural selection theory and so we just had a dead end to our survivability baked in, not so different than how the opposite phenomenon of senescence in cephalopods ends their lives
    matthewdgreen · 1791029251 · focus · HN ↗
    Everyone involved in this discussion understands that evolution doesn’t create things for a purpose, that it’s just the result of selection pressures. Everyone also uses the more active phrasing because it’s much more convenient. Unless you think you’re talking to someone who genuinely doesn’t understand the nature of the process, it’s not useful to be pedantic about it.
    yieldcrv · 1791038020 · focus · HN ↗
    We’re agreeing actually and not talking to you at all
    TJSomething · 1791015918 · focus · HN ↗
    There's the grandmother hypothesis that holds we could just not have menopause and reproduce more, but we don't because there's greater evolutionary advantage for having the elderly provide support to their kin. Maybe this type of kin selection is bounded by consanguinity though, and that limits the advantage? Or maybe population pressure discourages family units from getting too large?
    yieldcrv · 1791038142 · focus · HN ↗
    That’s the kind of evolutionary explanation that doesn’t fit natural selection at all in any time period
    You would need to explain how populations who did those things were selected against
    Instead of the more aligned reality that there was a random attractive or forceful menopausal mutant that popped out alot of babies or put alot of babies in others
    speaking of attractive, what we see now is that older women are selected against and everything considered attractive is correlated to ability of carrying a pregnancy to term. which came first? impossible for me to say, would older women have many more pregnancies if the menopause never happened? the viable eggs would have still gone towards zero, unlike other mammals and beings
    kakacik · 1791022017 · focus · HN ↗
    Evolution doesn't care at all, its just environment pressures and whatever organisms do within it. It can very well lead to some dead ends and sub-optimal long term choices.
    There will come time when we will grok all this 100% and then can setup whatever we want (its just a bunch of molecules acting predictably), but we are very far from there and there is no point discussing this even for our grandchildren. We will have cyberpunk implants way sooner.
    someonebaggy · 1791032075 · focus · HN ↗
    Evolution doesn't care about anything. Evolution is a descriptive force, not prescriptive. It boils down to the statement that things which copy themselves, we have lots of, which should seem almost like a tautology. It has no goal or purpose. It's an extremely random process and the apparent purposefulness is mostly just the result of that random walk having billions of years to run.
    Terr_ · 1790982796 · focus · HN ↗
    > wondered whether cancers in humans are a failsafe
    I don't think so, but in the context of theories that are more-interesting than "stuff just breaks sometimes", I'd like to suggest the atavistic aspect.
    Some cancers resemble a return towards unicellularity, as if "newer" multicellular rules have broken down. Not in any remotely-effective "our genes shall survive the dark times as goo" way, though.
    coderintherye · 1790983499 · focus · HN ↗
    Was actually a great article on this last week: <a href="https://dynomight.substack.com/p/liver" rel="nofollow">https://dynomight.substack.com/p/liver
    Discussion: <a href="https://news.ycombinator.com/item?id=49832938">https://news.ycombinator.com/item?id=49832938
    woadwarrior01 · 1791015321 · focus · HN ↗
    It's the other way around. Aging is the failsafe and cancer is the failure mode.
  3. [deleted] · 1790975469 · focus · HN ↗
    [deleted]
  4. alfiedotwtf · 1790989826 · focus · HN ↗
    Is “at the same time” a hard requirement?
  5. darubedarob · 1791008778 · focus · HN ↗
    [dead]
  6. anoncow · 1791027281 · focus · HN ↗
    We need more AI driven research
    tclancy · 1791045300 · focus · HN ↗
    What would the training data set be?
    HPsquared · 1791059943 · focus · HN ↗
    Some sort of horrific experimental laboratory.
3. everdrive · 1790972335 · focus · HN ↗
  I just don't understand. Wouldn't we have evolved in an environment with constant stress? Constant fear of disease, starvation, predation, attacks by neighboring tribes? Why would our body's natural response to our environment be to immediately grenade itself.
  1. atiedebee · 1790972638 · focus · HN ↗
    Considering that aging only happens later in life, it wouldn't have much of an effect on how efficient humans produce offspring, so it wouldn't be selected against. It is the same explanation for why Huntington's and Alzheimer's are still around.
    zorobo · 1790974424 · focus · HN ↗
    > Considering that aging only happens later in life,
    In other news, widows outlive their husbands.
    someonebaggy · 1791032408 · focus · HN ↗
    We are not talking about your amount of time on earth going up, we are talking about the biological mechanisms that happen later in life.
    Shitty-kitty · 1791010082 · focus · HN ↗
    There are 2 stages. Growth, till ~20 and then it switches to aging.
  2. teraflop · 1790972654 · focus · HN ↗
    I'm no biologist, but it's pretty easy to imagine a plausible mechanism.
    Stress doesn't cause your body to "immediately grenade itself", it causes gradual problems over an extended period. But you can imagine that evolutionarily speaking, a stressful situation would frequently be a situation involving imminent danger. A response that prioritizes short-term survival (e.g. releasing adrenaline and cortisol) regardless of the long-term consequences could easily improve evolutionary fitness.
  3. Lichtso · 1790972688 · focus · HN ↗
    There always has been a lot of stress, but there used to be relaxed moments as well. The issue is that we don't calm down anymore.
    Relevant video by Kurzgesagt – In a Nutshell: <a href="https://www.youtube.com/watch?v=Mo1A45ShcMo" rel="nofollow">https://www.youtube.com/watch?v=Mo1A45ShcMo
    someonebaggy · 1791032371 · focus · HN ↗
    That's a private equity AI slop channel. Any other reference?
    unfitted2545 · 1791045056 · focus · HN ↗
    <a href="https://en.wikipedia.org/wiki/Why_Zebras_Don%27t_Get_Ulcers" rel="nofollow">https://en.wikipedia.org/wiki/Why_Zebras_Don%27t_Get_Ulcers
    Sapolsky goes into great detail about the positive affects of stress in short durations, then demonstrates how these positives turn into negatives all over our body after being stressed for too long. Highly recommend!
  4. shevy-java · 1790973350 · focus · HN ↗
    > Wouldn't we have evolved in an environment with constant stress?
    Well, humans did not reach an old age if you look back to history. Only in recent times, say, 2000 years or so, or, if you want to be strict, the last 100 years, did humans reach very old ages. Back in older days, 30 years was considered old. Then 40 or so.
    FooBarWidget · 1790977743 · focus · HN ↗
    I heard that is mostly a myth due to misunderstanding what life expectancy means. It's an average over populations, pulled down mostly by enormous infant mortality. If you made it to 15 then there was a good chance you'll make it to 60.
  5. mbustamanter · 1790974289 · focus · HN ↗
    I suppose the stress was running away from a lion, not having the all-eating thought of meeting deadlines, a bad boss, backstabbing coworkers and so on, i.e. intense, but short, not persistent and chronic.
  6. LarsDu88 · 1790978478 · focus · HN ↗
    The idea that pre-agricultural societies are subjected to constant stress reflects modern biases somewhat. I remember years ago I saw a talk from Spencer Wells where he described how pre-agricultural life might have been like in Anatolia. Fields and fields of wild wheat stretching across the horizon. Long periods of seasonal abundance. Occasional periods of hunger and privation where families would often have to rely on the help of friends and acquantainces, with the understanding that one day the debt would be repaid if similar ill circumstances befell your neighbors.
    You can see some of how life might have been like in modern Papua New Guinea. War is nothing like modern warfare with artillery and guns. Its two groups of people firing arrows at each other from stand off distances while shouting at each other with minimal casualties. If you look at casualty rates from some of the early Greek warfare during the hoplite era, it's also surprisingly low.
    Also note that in this post, and from research, caloric restriction counteracts some of these inflammatory effects. In many ways modern life can be stressful in its own ways, especially as we remove ourselves more and more from the active lifestyles that necessitated survival in previous eras.
    justinclift · 1791005078 · focus · HN ↗
    > If you look at casualty rates from some of the early Greek warfare during the hoplite era, it's also surprisingly low.
    Didn't Genghis Khan wipe out entire cities? Like, every person inside, kind of thing. Women/children/etc included.
    LarsDu88 · 1791007348 · focus · HN ↗
    Genghis Khan did not live in a hunter gatherer society. His time was only 800 years ago... a time when gunpowder and intracontinental trade existed.
    Could arguably say the same of aLexander the Great and the classical era when casualries and army sizes balooned
  7. kulahan · 1790986820 · focus · HN ↗
    You only need to get to reproduction once, regularly, for a gene to keep getting passed on.
    Other mitigating factors: not eating much of the ultra-processed garbage we have today, regular high-intensity exercise, and a vastly-more interconnected community. Multigenerational homes make it easier to dump the kids off with grandma and go for a long hike with the wife or a party with the village or whatever. Etc. etc. etc.
    Were safer and healthier, but I don’t think we’re necessarily happier.
    Alive-in-2025 · 1791007237 · focus · HN ↗
    Yes, we damage ourselves with lack of exercise and bad food choices, likely much more stress (I guess fear of getting eaten by an animal is less than our modern stress about our quarterly reviews?). But also, because we can fix ourselves or repair or prevent/recover from many illnesses, we live vastly longer on average than earlier humans did.
    I'll take today.
    Shitty-kitty · 1791010478 · focus · HN ↗
    The stress has always been about food. Worrying about prey or a paycheck is the same thing.
    kulahan · 1791054754 · focus · HN ↗
    Again, you’re choosing health over unknowns. I am not saying this is bad, but I do hope you can at least see how the choice is not as obvious as we act like it is! We don’t necessarily have to go back to chasing mammoths with sticks to reach peak happiness. Maybe we just don’t need weight loss peptides and $4M in end-of-life care, for instance.
  8. dyauspitr · 1790995229 · focus · HN ↗
    I don’t think humans evolved under chronic stress conditions. I think we evolved under momentary stress conditions. Also stresses are heavily mitigated by community and our current society is generally one of chronic stress and low social connections. Inducing a moderate level of stress in your employees is literally the primary “motivational” tool for management in most places.
  9. laughing_man · 1791008602 · focus · HN ↗
    When humans evolved you'd have to be an incredibly lucky outlier to have lived long enough for stress to kill you.
  10. [deleted] · 1791068306 · focus · HN ↗
    [deleted]
4. fnord77 · 1790984744 · focus · HN ↗
  Yet, people who have had 100% stress-free lives get old and die like everyone else.
5. bglazer · 1790991939 · focus · HN ↗
  Yes we can do targeted (de)methylation at cells via a system called CRISPRon/off. It’s a CRISPR with the DNA cutting part deactivated but retaining the DNA binding part. They then attach a protein that adds methylation (DNMT3A) or removes it (TET1). So it’s a huge protein machine and it has only been tested in a petri dish (maybe mice, not sure).
  There’s a lot left to figure out. Delivery is hard. It would be hard to get it inside the right set of cells in a real person, you usually would only want to demethylate in a subset of cell types. There’s pretty steady progress being made in that area, but I think it will be several years before we fully solve that. Existing methods for doing this include hijacking a virus to deliver the DNA of the CRISPR system but those are one time only treatments because your immune system recognizes the virus and destroys it after one treatment. We use these viral delivery systems for some gene therapy treatments in real patients now. It presents a pretty terrible conundrum for patients who have to choose taking their one shot on an experimental treatment which may not work. Brave people!
  Anyways, yes it is possible but it’s quite early in development.
6. latexr · 1791017145 · focus · HN ↗
  > So chronic stress is one of the main contributors to aging.
  I remember seeing a documentary on that some two decades ago, so we’ve known it for a while. I haven’t watched it since so can’t say if it holds up, but to this day still remember the explanation of telomeres and the story of the baboons.
  It’s been uploaded to YouTube if you’re curious. For future readers, in case the link is dead, it’s called “Stress: Portrait of a Killer”.
  <a href="https://youtube.com/watch?v=eYG0ZuTv5rs" rel="nofollow">https://youtube.com/watch?v=eYG0ZuTv5rs
7. sajithdilshan · 1791029478 · focus · HN ↗
  I was thinking maybe some chemicals can help with chronic stress, but then again it would be more like a plaster than addressing the root cause.
  I guess the only permanent fix for stress in modern days is having enough money so one wouldn’t have to worry about it. As a single person I cannot think of any scenario where money cannot relieve my stress
  1. K0balt · 1791031674 · focus · HN ↗
    Problem is that just feeds the problematic paradigm. We need to be thinking carefully. Money, ultimately, is only used to pay wages. Nothing else. Resources and energy are never paid for, only labor, directly or indirectly.
    So we need to consider, what are we paying for that doesn’t translate efficiently to labor? What are we paying for that is merely the externalitization of costs? Of legislative capture so that otherwise communal resources can be monetised? Rent extraction from community created commons?
    There are reasons that modern humans spend much more of their time struggling to make ends meet than primitive humans, and a reason why people live much more comfortably with less struggle and a better life balance in some countries versus others. Money is incredibly useful, but it also serves to hide unjust and inequitable mechanisms that create perverse incentives that create a situation where every shred of excess value that a person sheds becomes mandatory just to keep your head above water, creating a condition of eternal struggle up to the absolute limit of endurance if you allow yourself to follow the dots on the floor.
    Obviously looking up and looking around, subverting the dominant paradigm, and eschewing “what you are supposed to do(c) “ can work, with risks, but perhaps it’s time to question whether the unrestricted amassing of resources by a few at the expense of everyone else is the right answer to the situations we are confronting?
    Idk, crazy talk, right?
    sajithdilshan · 1791033075 · focus · HN ↗
    You're over analysing it. If I didn't have to worry about money, I would just book a vacation in Italy and that would completely take my stress away
    pasquinelli · 1791034060 · focus · HN ↗
    i bet it wouldn't.
    you'd probably get sick on vacation and make your situation worse by obsessing over how you wish you weren't sick, in exactly the same way that you now obsess over how you wish you had more money than you do.
    sajithdilshan · 1791034315 · focus · HN ↗
    I disagree, I cannot explain it, but I’m always healthy and happy and worry free whenever I’m in Italy
    pasquinelli · 1791035208 · focus · HN ↗
    do you live close to italy?
    if not, then you must have a lot of money to have visited multiple times.
    sampullman · 1791034812 · focus · HN ↗
    I got sick on the flight during my last vacation, but I'd splurged on business class so it was still awesome. Took some Tylenol the next couple days and had a fantastic time.
    No need to stress about money either, as long as you have enough to cover your basic needs, and live in a country with universal healthcare.
  2. pasquinelli · 1791033766 · focus · HN ↗
    i think you're mixing up psychological stress and cellular stress.
    as for psychological stress, you will never have enough of anything, or be free enough from anything, or any combination, to be safe from stress.
    sajithdilshan · 1791034191 · focus · HN ↗
    I get what you mean. Human greed has no bounds. But if one can really discipline themselves then I think it’s possible to be stress free with proper planning and money
    pasquinelli · 1791035421 · focus · HN ↗
    yeah maybe, but regardless you'll still have pretty close to the same load of, like, biomolecular stress that causes aging.

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