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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. 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]

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