Thread

Loss of cell identity drives human aging: Two new papers

368 points · 183 comments · bookofjoe

Loading the complete thread in the background. This saved snapshot is available now. Refresh

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 practical fusion, rather than risking human extinction.
    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.
    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 "marketing" (or "propaganda" if you prefer the term).
    lofaszvanitt · 1791068138 · focus · HN ↗
    The bad news is that all this happens in the US. They gonna wmd themselves and potentially everyone else with this stuff.
    jodrellblank · 1791038313 · focus · HN ↗
    > "we can just turn off the data center if we need to"
    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" with no failover, no redundancy, and that the person doing frontier AI research sees a problem as it starts and has enough influence to get a whole datacenter shutdown, and that nobody will power it back on, and that nobody else on the planet will be at a similar point in their research, is naieve.
    Assuming that there will even be a simple critical point that someone will see, and that they will recognise it, and that this will work in scenarios with a hostile superintelligence, and that there will be time for a human-scale response once the problem becomes visible, are also not reassuring assumptions.
    That is, if it never happens or an AI is friendly, we won't need to turn off a datacenter. If we're talking of a hostile superintelligence which has been trained on all human writing about tactics and strategy and deception, which out-thinks a genius human, responds in microseconds, and has ample time to plot while deceiving us before it makes an obvious move, then turning off a datacenter is way too little, too late.
    > "Carbon capture is a joke.. It's not feasible."
    If only AI could genetically engineer trees to grow as fast as bamboo.
    > "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 it 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 for that, 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 AI researchers employee who can’t ask for a data centre to be shut down, can call the military in on a Meta data center by… ringing them up and telling them a self improving AGI is probably about to destroy the world and they need to attack an American company on the say-so of a nobody?
    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 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.
    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
    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 ↗
    [delayed]
    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. lofaszvanitt · 1791068306 · focus · HN ↗
    These fears affect the normal people. Not the psychos. Psychos are in control, they thrive in adverse environments, that's why they create these environments for the masses. They are viruses in human form. And need to be eliminated, removed from power asap.
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.
Chance-Device · 1790967609 · focus · HN ↗
I suspect that epigenetic aging is adaptive; a deliberately programmed sequence wherein genes more likely to contribute to age-related mortality are shut down progressively. This being in response to random genetic damage accumulating at a predictable rate.
What we think of as aging then becomes primarily the epigenetic response to the problem of DNA damage, much like the symptoms of a virus are mostly the result of the immune response rather than the virus’s direct effects.
1. api · 1790969470 · focus · HN ↗
  There's a lot of indirect evidence for this from the fact that some naive attempts at stopping aging give you cancer, like turning telomerase on indiscriminately.
  Almost everything in nature has multiple functions or causes, but one cause of aging is probably an evolutionary compromise between longevity and not getting cancer.
  One option, I guess, would be turning the guard rails off and just getting incredibly good at treating cancer or inventing some extraneous cancer detection and killing mechanism.
  1. Chance-Device · 1790969648 · focus · HN ↗
    > one cause of aging is probably an evolutionary compromise between longevity and not getting cancer
    Yes, and proteinopathies, and likely lots else besides. We probably don’t even understand the error modes that aging protects against.
  2. Retric · 1790972524 · focus · HN ↗
    It’s rarely such a simple tradeoff that only two things are being optimized.
    Cancer is extremely rare as a cause of death in wild animals. Again is more common but late enough that reproduction has produced multiple offspring.
    Energy expenditure isn’t something we’re concerned with but drives a great deal of evolutionary optimization.
  3. kulahan · 1790987029 · focus · HN ↗
    We all get cancer every day, and our body destroys it. When it finally fails to identify one, you get a tumor. If we’re doing something that massively increases cancer rates, we’d likely need a daily pill of some kind, or we’d be getting screened for cancer twice a year or something.
2. shevy-java · 1790973731 · focus · HN ↗
  This assumes there are genes that:
  a) contribute to age-related mortality, and
  b) shutting down helps combat aging.
  Can you state which genes these are that do that? Because I don't know of any.
  Plus, many genes have pleiotropic effects. There is no specific aging gene.
  On top of that, aging is a word that combines to many different factors. For instance, progeria was called accelerated aging. Well, turns out you have a mutation in lamin A. So, it is about cytoskeletal structure that is defect, rather than aging in itself. Of course the effects that this has, looks like an older person then, so it is related to aging. But one can not say it is "accelerated aging" as such. People having a normal lamin A allele still age nonetheless. So the whole term is problematic. And you can find many more such descriptions where xyz is about aging. Well, most of that it is about damage rather than aging. The Hayflick limit, though, is not about damage; that's just that cells fatigue for some reason when their telomeres shorten, but I have not yet read a sound explanations about why that is the case - after all there must be a mechanism in place.
flopsamjetsam · 1790974128 · focus · HN ↗
The two papers:
* <a href="https://www.nature.com/articles/s41586-026-10955-0" rel="nofollow">https://www.nature.com/articles/s41586-026-10955-0
* <a href="https://www.cell.com/cell/abstract/S0092-8674(25)00853-0" rel="nofollow">https://www.cell.com/cell/abstract/S0092-8674(25)00853-0
1. anotherpaul · 1791016369 · focus · HN ↗
  Neither is open access. A sad state of affair in 2026
  1. thangalin · 1791042778 · focus · HN ↗
    <a href="https://sci-net.xyz/10.1038/s41586-026-10955-0" rel="nofollow">https://sci-net.xyz/10.1038/s41586-026-10955-0
    <a href="https://sci-net.xyz/10.1016/j.cell.2025.07.031" rel="nofollow">https://sci-net.xyz/10.1016/j.cell.2025.07.031
egglinton · 1790977646 · focus · HN ↗
These papers simply present the accumulated damage hypothesis with new window dressing. They do not account for the known facts.
The article about these papers does not present a mechanism that would account for the Hayflick Limit.
Nor does it explain why dogs, for example, age and die more quickly than humans. If there is a mechanism of epigenetic drift that would explain this, I do not see it in the article.
The obvious answer to senescence is that we are programmed to do it. Cells die when they are supposed to die; if they don't, we have a problem.
Likewise, mammals die when they are supposed to. It takes less time to train a puppy to survive on its own than it takes to train a human. Hence, dogs are optimized to age and die more quickly. It's better for the species.
If we were not programmed to get old and die, evolution through natural selection would not work. We would never adapt to changing environments and our species would fail.
Aging and death is not an accident or a deterioration from damage or a drift away from a correct instruction set. It is an absolute hard necessity, without which we would all be long gone.
Stop wasting your time on nonsense articles like this and seek the mechanism that provides us as a species with the flexibility to adapt. Until we see aging and death as an core mechanism, we're going to be looking in the wrong place.
1. LarsDu88 · 1790979346 · focus · HN ↗
  A lot of fallacies and assumptions in this comment. First of all there is nothing in biology or evolution where the "good of the species" has any kind of bearing on natural selection. This is the group selection hypothesis that has numerous counterexamples. If anything selection happens at the gene level over the long run.
  There is also no clear reason we know of yet as to why a human being couldn't simply reach sexual maturity and hunting age faster. In fact, there might be at least some evidence other hominids did reach sexual maturity faster. It is not fully understood why humans take so long, but in animal kingdom terms we take roughly as long as the Asian Elephant to reach reproductive maturity. Almost certainly a tradeoff for achieving greater brain development and intelligence, but this could also simply be the consequences of being intelligent (e.g. it's easier to evolve for bigger skulls once ape intelligence surpasses a threshold where the apes are capable of committing to greater early childcare such that natural selection in absence of intelligence is weakened).
  If dogs were optimized to age and die more quickly for the betterment of the canine species, then you could make the same argument for humanity. That's simply not what's going on. Human ancestors in the past who traded generation time for greater intelligence, likely selfishly outcompeted those who did not, and those other hominids either died off or represent a much smaller allelic contribution to the extant human gene pool.
  For evolutionary biologists, aging and death similarly likely represent evolutionary tradeoffs. After reaching sexual maturity, as the probability of producing more offspring declines, so too does natural selection as alluded to in the article. Women are born with their entire compliment of ova and the rate of errors increases dramatically as they get older. Men have similar but more subtle issues with sperm generation. These error rate absolutely can be driven by mechanical stresses over time, and I would imagine could be driving much of the selective pressure that puts a cap on human longevity in the long run.
  1. someonebaggy · 1791032532 · focus · HN ↗
    Selection happens at all levels simultaneously in one big chaotic mess. Cancer cells are evolutionarily successful until they are not.
2. aksjfveoq · 1790981288 · focus · HN ↗
  This comment is nonesense.
  Stop spewing this claptrap as copium for your own mortality. Everything is natural and «part of life» till it isnt, like cervix cancer was like syphilis was like rheumatic fever was.
  You die because your DNA gets damaged and your cells lose the ability to repair themselves.
  You werent «programmed» to get alzheimer cancer artherosclerosis dementia and embolism. It’s not supposed to happen.
  gtfooh
3. jungturk · 1790982114 · focus · HN ↗
  "because they're supposed to" isn't a meaningful statement who is doing the supposing here? is this just an appeal to intelligent design?
4. andrewflnr · 1790984387 · focus · HN ↗
  > If we were not programmed to get old and die, evolution through natural selection would not work. We would never adapt to changing environments and our species would fail.
  An arbitrarily long-lived organism can not only keep reproducing (think trees), thus increasing its share of the future gene pool, but can care for its descendants, increasing their survival and further amplifying its genes. Besides, even without senescence nothing would live forever: accidents, fights, and disease would take their toll. Avoiding these would just be an even stronger selection pressure than they are currently.
5. jimberlage · 1790998656 · focus · HN ↗
  On a long enough timescale, things with a small chance of occurring become a virtual certainty. This includes the best of the human experience and the worst, which can get pretty dark.
  Why do people want to live forever?
  1. podocarp · 1790998875 · focus · HN ↗
    Fear, fear of the unknown, fear of death
    KronisLV · 1791042384 · focus · HN ↗
    > Fear, fear of the unknown, fear of death
    On one hand, death is the single most terrifying concept imaginable. In lieu of faith that explains it away, consider being conscious one moment, having been conscious most of your waking like and then it just ending. Never perceiving time, never having a thought, never experiencing everything, not even being aware of that and just being... gone. Forever.
    That's insanely fucked up, it being common or "inevitable" doesn't make it any less so.
    Like when my dad passed away, obviously I was sad about it happening and grieved it, at the same time I can acknwoledge that it was a small mercy that he wouldn't end up bedridden or trapped in a decaying body, and he didn't seem to fear it as much after having lived a long and fulfilling life and being religion-adjacent, but at the same time I very clearly don't like the idea of dying myself some day.
    So as far as I know, the only reasons for people to accept the concept of death and permanent nothingness is somewhere between either believing an "after" (and rejecting the possibility of it being a permanent end), being ignorant or indifferent about what it means, or simply being more busy with their present lives and such.
    It rubs me the wrong way, that alongside with research towards more graceful aging (if not to say reversing it, curing cancer etc.) should be way more of a priority for all of humanity, instead of the current realpolitik bullshit.
    podocarp · 1791114440 · focus · HN ↗
    I think what you're saying is you need purpose? So even with your dad not really fearing (or expressing his fear about) death you still feel that the benefits were him not having to suffer etc. etc.
    I think that's what religion gives, and it doesn't have to be organized religion. I'm not proselytizing, I'm just pointing out why across so many human cultures people always come up with stories and thoughts about the afterlife. The cold unknown means basically nothing and the fear I think comes from the nothingness -- imagine a life full of the sorrow and joys, and then it just vanishes. And worse of all, if nobody even remembers much it of it, it literally vanishes. For example if a war veteran never tells his experiences to anyone, he basically just vanished from earth and one can ask so did the things he went through happen? If a tree falls and nobody hears it and all that.
    I'm probably expressing it poorly but I've been thinking about it too after experiencing some loss too. In my case the person just graduated college. I think the dead have it easy, the suffering lies with the living…
  2. goatlover · 1791003251 · focus · HN ↗
    There is a vast amount of difference between growing old and dying by 100+ and living until the heat death of the Universe trillions of years from now. Surely something in between, say centuries or millenia without death from the ravages of old age would be ideal.
    tclancy · 1791045672 · focus · HN ↗
    I wonder about this at 50. Being an odd duck, my philosophy here is based on a Conan story about a race that lived forever and had an actual ceremony for when the decided to end things.
    Stuff accretes over time. One shoulder, the opposite arm due to compensation, both big toes, etc. But take away all of that and there are still accretions: I’ve started to track the point where I know more dead people than live ones. Of course you can compensate for this and my wife and I have a wide social circle that we tend like good gardeners, but that feels like a delaying action. At some point I’m going to hit, “Hey, fellow kids!” if I haven’t already. Put more simply, will there come a time when the idea of falling in love with one more dog just to lose them will feel like a bad bet?
  3. someonebaggy · 1791032667 · focus · HN ↗
    Why do people want to die?
    I think if humans didn't age past 20, we'd eventually get tired of life and want to die on our own terms instead of on a timer. We wouldn't stick around until the sun exploded.
6. aeve890 · 1791001219 · focus · HN ↗
  >The obvious answer to senescence is that we are programmed to do it. Cells die when they are supposed to die
  More handwaving like this and we'll name the hurricane after you.
7. NL807 · 1791002607 · focus · HN ↗
  >Aging and death is not an accident or a deterioration from damage or a drift away from a correct instruction set. It is an absolute hard necessity, without which we would all be long gone.
  Not buying this at all. This view is completely at odds against multicellular organisms that can literally clone themselves.
  Everything we know about aging so far points towards the deterioration of renewal mechanisms that keeps our system functional. Cells die due to a host of reasons besides programming. For example, they may become non-functional and eliminated by the immune system.
  1. someonebaggy · 1791032567 · focus · HN ↗
    But that deterioration seems to be programmed, or at least not selected against, which is surprising. We know animals with drastically different rates of aging, and some that are effectively immortal.
8. goatlover · 1791003476 · focus · HN ↗
  There are giant tortoises that live longer than humans. I don't think they require a prolonged childhood for training to become successful adults.
formvoltron · 1790979097 · focus · HN ↗
No mention of new limit.
In fact there is very little talk about new limit. But what they are doing seems impressive and important.
randomImmigrant · 1790983398 · focus · HN ↗
I’m a bit mystified by the authors of the papers and the blog ignoring circadian rhythms. Three timescales, and there’s one daily oscillation in the middle that clearly integrates these shorter signals and is known impact aging… why is that not part of this picture?
1. huflungdung · 1790985236 · focus · HN ↗
  [dead]
2. JacobAsmuth · 1790985909 · focus · HN ↗
  Furthermore - I am stunned that the authors seem to have completely eschewed the Krebs cycle!
[deleted] · 1790993931 · focus · HN ↗
[deleted]
octoberfranklin · 1790994472 · focus · HN ↗
This webpage is a great example of why AI-generated illustrations are counterproductive. They make your webpage look flashy to somebody just scrolling by, but contribute almost nothing to the actual content.
1. justinclift · 1791006427 · focus · HN ↗
  Also, they signal that AI was definitely involved in the process, which can mean the writing itself is generated garbage.
2. ForgotMyUUID · 1791031282 · focus · HN ↗
  I find them harmful to watch: always feel dizzy afterwards. Surprisingly, i could find no studies on that effect.
SubiculumCode · 1791009053 · focus · HN ↗
That's why knees hurt in old age? They forgot they were knees, decided they were sentient cheese?
1. rf15 · 1791009313 · focus · HN ↗
  ah, the famous cheese knees disease
  1. da_chicken · 1791012956 · focus · HN ↗
    Somebody call Dr. Mario!
  2. BLKNSLVR · 1791036638 · focus · HN ↗
    > "Through three cheese trees, three free fleas flew. While these fleas flew, freezy breeze blew. Freezy breeze made these three trees freeze. Freezy trees made these trees' cheese freeze. That's what made these three free fleas sneeze."
    Fox in Socks. Magnificent for all time.
2. Levitating · 1791022725 · focus · HN ↗
  I think knees also just wear out.
3. baxtr · 1791027961 · focus · HN ↗
  Maybe that’s why it’s important to keep working out?
  Don’t let them forget what they were meant for!
  1. jarjoura · 1791056006 · focus · HN ↗
    I think mine must have desperately wanted to stop being knees to stop all the abuse of sport and years of working out they had to endure.
4. HexPhantom · 1791033746 · focus · HN ↗
  Pretty much. One day your cartilage wakes up and goes "I've done enough cartilage work, I'm a fibroblast now"
5. BLKNSLVR · 1791036328 · focus · HN ↗
  Going purely by sound, some of my knee internals seem to think they're meant to be cellophane.
  1. tclancy · 1791045278 · focus · HN ↗
    I think I would prefer that to mine which seem to have small fireworks someone forgot about in them now.
boccko · 1791012689 · focus · HN ↗
What a perfect metaphor for modern societies.
IndiaInfraNotes · 1791015108 · focus · HN ↗
[dead]
rotbart · 1791018164 · focus · HN ↗
The strongest evidence we have of the reversibility of epigenetic aging, as well as its limitations -- are embryos which undergo an epigenetic reset.
After fertilisation, the embryo strips the father's DNA of its age-linked chemical tags and swaps its packaging, destroys his mitochondria, rebuilds telomeres, and clears damaged proteins, though it can't undo the DNA mutations sperm gather as men age.
(those that result in an non viable embryo result in miscarriage.)
1. darkerside · 1791021494 · focus · HN ↗
  Hmmm seems high stakes
  1. dzonga · 1791030535 · focus · HN ↗
    pregnancies are high stakes.
    it's actually surprising they happen at all given the very low probability of everything going right.
    le-mark · 1791061424 · focus · HN ↗
    > very low probability of everything going right.
    Looking around at 8 billion+ people on this planet, is the probability that low?
    mitxela · 1791110064 · focus · HN ↗
    It's about the same as the probability that your computer happens to only execute valid instructions.
  2. K0balt · 1791030627 · focus · HN ↗
    Yeah, as a 58 year old fetus…that sounds problematic.
2. jijijijij · 1791030973 · focus · HN ↗
  Embryogenesis is an early fail-fast process. The vast majority of mutations and instabilities are caught through developmental checkpoints. Every living human passed a ruthless selection process in the womb.
  So part of the magic of that aging reversal is simply abandoning what doesn't stick. You can't do that to a grown human, obviously.
  1. someonebaggy · 1791032000 · focus · HN ↗
    You can at the cellular level. There's a hypothesis that low levels of caloric restriction or oxidative stress are essential, because they weed out underperforming cells, which are replaced.
    pasquinelli · 1791033035 · focus · HN ↗
    do you mean to say low levels of caloric restriction, or low levels of caloric intake?
    someonebaggy · 1791039112 · focus · HN ↗
    A small amount of adverse conditions.
    tclancy · 1791045212 · focus · HN ↗
    If that works, just think what a heroic amount could do!
    wizzwizz4 · 1791045955 · focus · HN ↗
    It can weed out all your cells!
    meowkit · 1791046256 · focus · HN ↗
    Common response and completely misses the point. Its about dosage.
    Water will quench your thirst. You can also drown in it.
    Fire will warm your hands. Sticking you hands in a fire is a bad idea.
    Acute stress, induced by exercise / caloric restriction, is feedback to trigger beneficial cellular behavior.
    Chronic stress, no exercise / eating poorly through starvation or overconsumption (a “heroic dose”) will certainly kill you sooner.
    gozucito · 1791054057 · focus · HN ↗
    I think it was a joke :)
    jijijijij · 1791037243 · focus · HN ↗
    This is not at all comparable to the extent of embryonic rejuvenation. Lol.
    Caloric restriction etc. just aids cellular housekeeping. The processes in maintaining gametic immortality are much more radical and transformative. Somatic and gametic genetics are governed completely differently.
    agumonkey · 1791043442 · focus · HN ↗
    Do you have books or articles to read about this ?
    jijijijij · 1791049714 · focus · HN ↗
    All of it is a matter of active research, as this relates to the evolution of sex/sexual reproduction, which, contrary to popular belief, is still an unsolved problem in biology. Classical evolutionary theory cannot explain sexual evolution. Any book about "why?" will either be highly opinionated, agenda-driven, out-dated, or simplistic (as are my comments here).
    I am not a biologist, so I can not refer to or evaluate any meaningful recent papers on the matter. However, I can recommend the podcast 'Big Biology', which dives into current biology research, theory and philosophy, including sexual evolution.
    You may start here: <a href="https://en.wikipedia.org/wiki/Evolution_of_sexual_reproduction" rel="nofollow">https://en.wikipedia.org/wiki/Evolution_of_sexual_reproducti...
    Richard Dawkins' 'The Selfish Gene' is also an excellent read/audiobook. His specific theories of the evolutionary "unit" have been disproven, but his argumentation teaches a lot about "evolutionary thinking". I really wish he stuck with biology and science education instead of becoming this reactionary giga twat.
    agumonkey · 1791050866 · focus · HN ↗
    thanks a lot, i'll start with those.
    if you know other websites or podcasts similar to big biology i'd be glad, i've been trying to setup some list of sources on that topic
    thanks again
    jijijijij · 1791054227 · focus · HN ↗
    Sorry, it's not my main interest right now, so I am out-of-the-loop.
    Last time I checked, Big Biology was kinda unique going beyond basic popsci, while still remaining interesting and engaging. I think biologists are not the most technically inclined, not really drawn to podcasting. And it's also not the hottest of topics right now, specific research PR and educational voices aren't funded well. There are some journal/university etc. associated everybody-has-a-podcast-now podcasts, but I found them to be rather boring and dry. Individual episodes of the Huberman/Lex Fridman type edgelord podcasts may also be occasionally interesting, but the signal to noise ratio is poor, with a heavy bias towards overconfident and narcissistic guests speaking with false authority, lots of explanatory speculation presented as facts, pronounced political confirmation bias.
    Maybe take a well presented episode on Big Biology and see where else respective guests speak or publish?
    Ratelman · 1791053822 · focus · HN ↗
    What do you mean when you say sexual evolution?
    jijijijij · 1791056081 · focus · HN ↗
    The evolution of sex and sexual reproduction, as opposed to other means of reproduction. It is inherently tied to the difference in genetic maintenance/repair mechanisms between germline and somatic cells. See wiki link above.
    yrjrjjrjjtjjr · 1791064298 · focus · HN ↗
    Sexual reproduction can remove bad mutations. Imagine two parents. One has bad mutations m1. Other has bad mutation m2. They have three children. The first gets only m2. The second gets both and dies. The third inherits neither.
    Even though neither parent was fully healthy, one of the children was. Asexual reproduction cannot do this.
    jijijijij · 1791072763 · focus · HN ↗
    The scenario you are painting only exists with sexual reproduction, so it's circular reasoning.
    mitxela · 1791109888 · focus · HN ↗
    Organisms can only have bad mutations if they reproduce sexually?
    jijijijij · 1791124684 · focus · HN ↗
    No, of course not. But having diploid, paternal and maternal DNA is something you need sexual reproduction for.
    yrjrjjrjjtjjr · 1791134856 · focus · HN ↗
    Fitness is not a binary.
    jijijijij · 1791138142 · focus · HN ↗
    Why does evolution have to pick one of them?
    You are not really thinking this through. How would a fitness reducing mutation become a feature of a genetic line in the first place in asexual reproduction? The "silent" partial carrier dynamic of genetic defects is a problem exclusive to sexually reproducing organisms.
    How can sexual reproduction "get rid of them"?
    Play it out for a few generations, you will see, there is a frequency equilibrium. We've done this in school with paper, but if you know some programming, it's an easy exercise. Anyway, unless being very detrimental for partial carriers, the bad allele is gonna stay in the gene pool.
    mitxela · 1791144933 · focus · HN ↗
    Imagine a flax bush with a mutation that causes smaller leaves and a separate one that makes it live longer. In asexual reproduction it's probably going to be about as prevalent as the wild type (the default without these mutations). In sexual reproduction the repeated shuffling of genes will eventually produce one with the longer life but without the smaller leaves.
    jijijijij · 1791148590 · focus · HN ↗
    You are shifting the goalpost. It's not the original argument anymore.
    yrjrjjrjjtjjr · 1791172949 · focus · HN ↗
    > How would a fitness reducing mutation become a feature of a genetic line in the first place in asexual reproduction?
    A random mutation. Especially when combined with the founder effect or some other genetic bottlenecking.
    rsync · 1791056493 · focus · HN ↗
    I think the Nick Lane books are quite good - especially:
    <a href="https://en.wikipedia.org/wiki/Power,_Sex,_Suicide" rel="nofollow">https://en.wikipedia.org/wiki/Power,_Sex,_Suicide
    which, IIRC, discussed the notion of an semi-autonomous population of mitochondria in long lived tissues (like muscle) which could be curated over ones lifetime by high intensity exercise stress. Future mitochondria in these long-lived tissues would then not be descended from the poorer performing members who were weeded out through apoptosis.
  2. HexPhantom · 1791033466 · focus · HN ↗
    An adult therapy has to rejuvenate the cells you already have, in place, without breaking tissue function or creating cancer. Much less room for error
    jijijijij · 1791036682 · focus · HN ↗
    Yes. Early embryogenesis has some weird complexity, scientists suspect it's evolved to be a genetic stress test. Mind you, mutation in sexual reproduction isn't at all just accidental. The cross-over stage in meiosis always recombines the chromosomal information randomly (to increase environmental adaptability with the slow rate of sexual reproduction). There is no concept of a "gene" there, the cuts can happen in the middle of anything important, too. This intentional instability needs to be accounted for, biologically. Before anyone even detects pregnancy, a lot of non-viable genetics have been aborted by the body. As tragic as they are for the becoming parents, miscarriages are a good thing, not misfortune. It's exactly this fail-fast selection process weeding through failed random recombination samples, which likely would have caused severe functional problems later anyway.
    You cannot do a selective genetic stress test on a developed organism like that. But without it, the rejuvenation process wouldn't be safe, rather a guarantee for cancer and metabolic dysfunction. E.g. senescence is a way for the body to sort out misbehaving/dysfunctional cells without downright killing them. Rejuvenating such cells would be catastrophic. At any point in time, there are malignant cells somewhere in the body, which are constantly snatched by the immune system. In fact, "rejuvenation"/immortality is a hallmark of cancerous transformation. And let's not forget, the embryonic development isn't fully self-governed. The mother's body also checks its signaling and may abort anything funky. A developed organism doesn't have this external oversight. Auto-immunity is all there is and that can become malignant too.
    Did you know, with age, men's somatic cells increasing lack the whole Y-chromosome? It's not at all mission critical and just got lost at some point during mitosis, no biggie, but I think it shows the extent of genetic disarray in somatic cells.
    soyboy_supreme · 1791184543 · focus · HN ↗
    [dead]
    LogicFailsMe · 1791046023 · focus · HN ↗
    If you cracked this and gave everybody another ~50 years, that's probably enough time to crack cancer across the board. But not everybody is going to want those extra years. And I'd only want them if they were healthy active years.
  3. lostmsu · 1791050882 · focus · HN ↗
    It is not that ruthless though, is it? Because it is limited by the number of egg cells.
    jijijijij · 1791055040 · focus · HN ↗
    Given the fact the large majority of embryos die early after conception, I would call it quite ruthless. And of course, there is intense gamete selection beforehand too.
  4. Terr_ · 1791081495 · focus · HN ↗
    [delayed]
3. HexPhantom · 1791033313 · focus · HN ↗
  Embryos are probably the clearest proof that at least some of what we call biological aging is reversible rather than simply accumulated irreversible damage
  1. jjallen · 1791034681 · focus · HN ↗
    Is this just a summary of the parent post? Seems like you just repeated what they said.
    anamexis · 1791035349 · focus · HN ↗
    I'm glad they did!
    rootsudo · 1791040337 · focus · HN ↗
    Yes but it helps context. This is HN and this is how comments used to be.
    DenisM · 1791049436 · focus · HN ↗
    I see this a bit recently. Karma grinding?
4. jarjoura · 1791056695 · focus · HN ↗
  Apparently mammal DNA lost its ability to self-repair adult cells somewhere along the way, maybe when we evolved to evade threats post-dinosaurs.
alescalaios · 1791021335 · focus · HN ↗
[dead]
lifty · 1791028381 · focus · HN ↗
Ever since I discovered Michael Levin and his work, I started seeing biological systems as information systems. And these papers seem to point in the same direction.
1. canadiantim · 1791032126 · focus · HN ↗
  What has Michael Levin to say about biological systems as information?
  1. lifty · 1791038612 · focus · HN ↗
    That there is another layer on top of the biological/genetic system which allows cells to organise themselves and pursue goals, taking advantage of bio-electricity (gap junctions in cells) in order to communicate. He uses the hardware vs software analogy which I think fits well. The theory sounds a bit wacky initially but all of it has been corroborated in empirical testing in his lab.
    I am not a biologist but it seems to me, based on the podcasts that I hear, that his theories are becoming more accepted and there are also more and more people from outside the biology field looking into his theories of "diverse intelligence"; he has a podcast where he discusses related things with scientists from various fields.
    canadiantim · 1791120422 · focus · HN ↗
    Yeah this theory has been part of biology for a long time in different forms, I also subscribe to it. You may like to look into Rupert Sheldrake’s morphogenetic fields which is a recent depiction of it too that is very interesting
2. RangerScience · 1791034688 · focus · HN ↗
  IMO, whatever the new / dominant engineering paradigm is, is what we use to understand everything else.
  Architecture, then clockwork, then steam, then machines, now computing.
  I don’t think it’s wrong in anyway to do this, but I do think it’s interesting!
  1. delecti · 1791045272 · focus · HN ↗
    Yeah. I think linguistic relativism is oversimplifying, or possibly reversed, but it sure does feel truthy in certain lights.
3. AndrewKemendo · 1791055926 · focus · HN ↗
  In case you want to see more, Levin was the first speaker on day to two of the AGI 26 conference in SF in July:
  <a href="https://www.youtube.com/live/kQBwtgkHnC4?si=X_QnJULdoPX5jOxY" rel="nofollow">https://www.youtube.com/live/kQBwtgkHnC4?si=X_QnJULdoPX5jOxY
  Hananel from that lab gave a talk about this at the Boston AGI society meetup (bad sound but captions work:
  <a href="https://m.youtube.com/watch?v=3TP1scXfMDg" rel="nofollow">https://m.youtube.com/watch?v=3TP1scXfMDg
dejj · 1791028648 · focus · HN ↗
> destroys his mitochondria Fine print: only the father’s. Maternal mitochondria from the egg are dormant at first and activated after 10 (?) cell divisions. Those mitochondria are never reset, and return to dormant state as soon as specialization into egg cells allows them, afaik.
Notwithstanding heteroplasmic (paternal) mitochondria making it into the cell in 8% of cases, with unknown effects.
1. HexPhantom · 1791033559 · focus · HN ↗
  So the mitochondrial part of the "reset" is less like rejuvenating an old population and more like starting from a maternally inherited population that was largely kept out of the metabolic action in the first place
HexPhantom · 1791032734 · focus · HN ↗
[dead]
black_13 · 1791037068 · focus · HN ↗
[dead]
[deleted] · 1791062261 · focus · HN ↗
[deleted]

Open on Hacker News to reply ↗

Unofficial Hacker News client; not affiliated with Y Combinator.