subcosmos 6 years ago

The effect that they observe makes sense, implicitly, but I struggle to see a causal link here.

The nucleolus is the site of ribosome synthesis, and ribosomes are needed to make proteins. Under caloric restriction, the growth pathways in the cell get turned down, and protein translation is held back until resources become available again. It makes sense that the cell would stop synthesizing ribosomes, which are HUGE structures that take lots of energy to make.

So I would say that reduced protein translation is a hallmark of longevity, and the methionine restriction experiments support that. The nucleolus getting smaller is likely one of the many effects of this adaptation.

I agree with the author however that this is a great and easily-measured microscopic phenotype. Perhaps this can lead to awesome assays of cellular aging, and perhaps even drug screening for compounds that are rejuvenating.

reasonattlm 6 years ago

It is funny what does and does not catch the attention of the popular science press. This really isn't all that important as an example of research. It is a very incremental increment in exploring the connections related to cellular housekeeping and stress responses. There really isn't anything that can be done with this knowledge that couldn't be done already with the existing knowledge of the ribosome.

This is an example of the broad, dominant class of aging research that is purely investigative. Most research into the detailed mechanisms of degenerative aging is very far removed from any thought of application, and it is lucky happenstance when such an opportunity does arise.

Unfortunately, systems very closely tied to cellular housekeeping, or responses to stress, or replication seem unlikely to result in the foundations of truly effective therapies. We can look at calorie restriction or exercise, both of which alter all of the above items quite profoundly and throughout the body, to see the plausible benefits that might be attained through manipulation of these fundamental aspect of cellular behavior. We can also look at the past fifteen years of research into these mechanisms to see just how slow and expensive it is to try to produce therapies to slow aging - there is very little to show for all of the effort invested.

Searching for means to adjust metabolism to modestly slow aging is not a winning strategy; the expected benefits are just not large enough. We must find ways to add decades of vigorous life, not just a few few healthy years.

Tharkun 6 years ago

So another datapoint indicating that caloric restriction might be a good idea, with a plausible sounding mechanism of action.

  • KasianFranks 6 years ago

    Are you trying to be another idiot: Statistical modeling of biomedical corpora: mining the Caenorhabditis Genetic Center Bibliography for genes related to life span - Blei DM, Franks K, Jordan MI, Mian IS. - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533868 - it's about buying time.

    • subcosmos 6 years ago

      Kinda arrogant to call the parent an idiot and then link to your own paper ....

      • KasianFranks 6 years ago

        True. And you have children. Better to exist than not exist.

        • Blahah 6 years ago

          You're both violating the community standards here (by calling people idiots) and really reaching by suggesting that a methodological paper about inferring information from C. elegans literature is somehow a clear rebuttal to the parent post.

          • KasianFranks 6 years ago

            Community sometimes has very little to do with what's true.

            • juancampa 6 years ago

              This guy sounds like a bot using some sort of generative NN with "toxicity" turned up to 11

              • KasianFranks 6 years ago

                Bingo, in part. We're also trying to determine who does not value existence.

                • subcosmos 6 years ago

                  Who is your creator, droid?

            • zenzian 6 years ago

              Hm, what an absolutely dimwitted and obtuse "scientist". I hope your career crashes and burns. You want to be heard? Make yourself a pleasure to be heard. I cannot believe you got anyone to work with you.

            • pstuart 6 years ago

              Yes. Also true is that toxic dialog does not move the discussion forward.

jatsign 6 years ago

Based on various stories that have popped up on HN in the last few years, there seems to be a lot of things inside us that might determine how long we live...

  • nonbel 6 years ago

    It's a fundamental problem with modern day medical research. Rational people would start from the principle that "every x is correlated somehow to every y" (in this case "every aspect of the human body and environment is related to aging"). Now that aspect is taken care of, so rational people can proceed to figuring out quantitative models of these relationships.

    However, the current paradigm is to reward people who check for "significant differences/correlations", which just means that they "discover" all these non-zero correlations. Basically it is a huge waste of time and money but it works really well to generate an endless series of breathless press releases.

    • cycrutchfield 6 years ago

      Go ahead and knock yourself out. If you think “creating a quantitative model” of senescence is easy for “rational people”, then go right ahead. Your Nobel prize awaits.

      • nonbel 6 years ago

        Well, I didn't study senescence but actually did do something similar.

        It required training myself in math, programming, history of the topic, and stats in addition to the normal grad school stuff (memorizing stuff for classes, data collection, etc) which amounted to about 3 years of working almost nonstop.

        Turns out nobody cared, all they wanted to know is if there was a significant difference between groups. My attempt caused me health, financial, and social problems for literally an anti-reward so I would not recommend anyone try it. I also don't believe anyone would get a nobel prize for that in the current environment, they would be ignored or fought against because some holy cows would need to be sacrificed.

        EDIT: As a more concrete example. Look at the pushback against Tomasetti & Vogelstein for daring to point out that there is a base rate of mutations per cell division and accumulated mutations lead to cancer, so cancers arise more often in tissues with more divisions. This is almost common sense, but people cannot handle it for some reason: https://www.theatlantic.com/science/archive/2017/03/no-cance...

        • toopsss 6 years ago

          Yes there are some idiots that dismissed the tomasetti and vogelsteinn paper due to it conflicting with their worldview, but they only got momentum because the original paper really was crap from even a critical scientific POV. What’s very ironic is that the problems with the paper seem to be the same things you’re bitching about in your post. No one smart is criticizing the paper for the “common sense” part, but because they actually tried to quantify it and their method was quite flawed.

          • nonbel 6 years ago

            What were the problems in that paper? The good stuff is that they were able to come up with estimates for stem cell divisions and were able to see a correlation with the cancer risk.

            The bad stuff was the usual misinterpreting correlation coefficients and p-values (this is standard, found in pretty much every paper) and that the data is messy/incomplete. I mean, sure more people should be working on figuring out the number of stem cell divisions by tissue and other nations should collect data of the same quality as SEER...

            If it was just another standard "smoking/sunlight/etc causes cancer" paper with the same issues there would not have been this response. It even says so in the atlantic, people think this information undermines their public health campaigns:

            >'The paper triggered a hailstorm of criticism. Some scientists chastised the methods. Why did they ignore common cancers like breast and prostate? Why did they only focus on the U.S.? Others accused the duo of undermining public health. Many personal choices, from quitting smoking to staying lean, can dramatically reduce one’s risk of cancers, but why would you bother if you read headlines saying that these diseases are “largely down to bad luck?”' https://www.theatlantic.com/science/archive/2017/03/no-cance...

        • i000 6 years ago

          I would suggest you do not use your personal failures and frustrations as justification to call other researchers work a waste of time. Please go ahead and explain to us how their contribution to science is a waste of time and money (you could for example contrast it with your own accomplishments).

          • nonbel 6 years ago

            There is nothing complicated about this problem: Discovering that an aspect of human cells/tissue plays a role in any aspect of human health is a waste of time because we already know this is true to begin with. Nothing has been learned.

            Now I am sure there is some other info in these papers that may be useful about how the nucleolus changes with age, etc but, like the OP noted, the headlines are all about "playing a role".

        • ackfoo 6 years ago

          Excellent answer to a sarcastic troll. The best and brightest are obviously not going into science, and those who do must learn to play the idiotic game for survival.

        • JPLeRouzic 6 years ago

          Nonbel, please do you have some pointer to your research?

          • nonbel 6 years ago

            Sorry but I specifically don't give examples using my former research in this light because these problems are very general. I don't want to seem like I place any blame on a specific organization, program, or person (nor contribute to anyone else doing so).

  • pjc50 6 years ago

    In a piece of software, there are a lot of things that might determine how long it runs before it crashes ...

combatentropy 6 years ago

  Nucleolus = ProteinFactoryFactory
  • subcosmos 6 years ago

    It makes little models, of factories

indescions_2018 6 years ago

Really excited to see YC Bio longevity startups when they launch.

Roritharr 6 years ago

So will my new born become immortal or not? Do I have a chance?

  • MikkoFinell 6 years ago

    I will give your offspring a 90% chance to get in on the longevity escape velocity. You get around 50% depending on your current age and general health. If you are close to 40 years old, and have been neglecting your health, then you might want to invest in cryogenics. Otherwise you want to invest in artificial intelligence and medical research.

  • ben_w 6 years ago

    Probably, yes. Even five years ago people were saying “we think the first immortal [1] has already been born, we just don’t know how old they are.”

    [1] As in no inherent old age, rather than un-killable.

  • subcosmos 6 years ago

    Your newborn has a chance, and that chance goes up if you participate in research.

  • ddorian43 6 years ago

    I still fail to see why the scintist-god would give you/me immortality unless we become their slaves ?

    Just give it to Bill Gates and he can hook you up with enough cash?

    • melling 6 years ago

      The need to head for the dystopian view is overwhelming?

      Of course, with some effort we might simply figure out how to double our lifespans to 160-200 years.

      Albert Einstein, for example, could still be alive discussing physics with Stephen Hawking.

      • obelix_ 6 years ago

        Bad example. Einstein wasn't exactly a 'life is worth living' advertisement by the time he reached old age. I doubt he would have taken the offer. Source - https://m.youtube.com/watch?v=zpTUjb-iKf4

        • melling 6 years ago

          Do you honestly expect people to watch an hour video to get your point?

          Pick two, or more, of your favorite scientists. Richard Feynman?

      • ddorian43 6 years ago

        What has happened with increasing lifespans till now ? Has wealth been more or less distributed ? Can we extrapolate 80 -> 200 years old ?

      • jacquesm 6 years ago

        Science advances with the death of prominent scientists who have become obstacles to progress. I see no reason why Hawkings or Einsteins would be exceptions to that rule.

        • MikkoFinell 6 years ago

          Yeah we can at last make some more progress in science, now that we're finally rid of Hawking.

          • jacquesm 6 years ago

            You are entirely missing the point.

            If Hawking and Einstein lived longer so would everybody else. And that would mean that a younger generation of scientists would have to wait much longer before their ideas could be discussed without opposition from the established elders who see their pet theories attacked by these uppity youngsters.

            The quote is a riff on what Max Planck, himself an eminent scientist said on the subject:

            "Science advances one funeral at a time."

            https://en.wikiquote.org/wiki/Max_Planck

            • MikkoFinell 6 years ago

              > And that would mean that a younger generation of scientists would have to wait much longer before their ideas could be discussed without opposition from the established elders who see their pet theories attacked by these uppity youngsters.

              Okay I will accept that premise for the sake of the argument even though I don't actually believe it's true.

              Based on that you go on to conclude it's a good thing that scientists die, so that science can keep advancing.

              You're essentially faced with a trolley problem, where pulling the lever one way will make everyone immortal at the cost of slowing down scientific progress, but pulling it the other way will euthanize everyone in the world, and euthanize the countless billions that might live in the future. Somehow your morals (or whatever you call it) tell you that euthanizing everyone is better than slowing down scientific progress. I disagree with you there.

              Why not even try to solve the problem some other way than killing everyone? I don't know, why not, say, create an off-world colony outside the reach of those evil progress-impeding elders. Just throwing ideas out there.

              Taking your logic to its limit, why not just kill every scientist after their first paper is published? But I don't think you actually want that, so lets hear your argument against my strawman.

              • magduf 6 years ago

                I also don't believe it's true. The entire nature of science is that theories are modified or discarded as new empirical evidence disproves them. This idea that established immortal scientists would cling to proven-false theories despite evidence from "uppity youngsters" just flies in the face of what science is all about.

                If he were talking about politics, he'd have a point, since there's a lot of irrational dogma in that field.

                Also, don't forget, if we can figure out how to eliminate aging, that also means we'll eliminate many (maybe all) things that go along with biological aging, such as the changes to the brain that cause older people to tend to be less adaptable (which really is a bit of a stereotype and not all that true; my 80 year old mother happily uses a laptop computer, smartphone, and tablet, while 30 years ago she wouldn't have dreamed of being like this).

                • neuromantik8086 6 years ago

                  > If he were talking about politics,

                  You seem to be operating under the assumption that science is apolitical. As someone who's worked in science, I can assure you that it is not. Many non-scientists listen to popularizers like Neil deGrasse-Tyson and come to believe in a very idealized model of how science operates when the de facto "nature of science" is more akin to what Thomas Kuhn describes in "The Structure of Scientific Revolutions". I really wish that NDT were a bit more forthcoming about his own experiences in science, seeing as how he barely made it through the grad school gauntlet himself. Ditto for Carl Sagan, who made a powerful enemy in Harold Urey (I can't find a link right now, but iirc Urey basically gave Carl a bomb of a recommendation letter that cost him a tenured position Harvard and compelled him to "settle" for Cornell).

                  In my personal experience (as well as the experience of many, many others if you dig deep enough into this), some scientists can be very egotistical to a point where they take a challenge to their theories as a personal affront, and will employ insanely Machiavellian tactics to suppress dissenting opinions (i.e., senior researchers are the ones who hold the purse when the NIH makes funding decisions).

                  • magduf 6 years ago

                    Problems like this can be mitigated or solved with policies, such as limiting tenure or forcing professors to move on after a certain term. We already do this with some politicians. What you're describing is really a problem with academia, not science in general. Corporations doing scientific work don't have those problems (they have other ones though), for instance.

                    • neuromantik8086 6 years ago

                      True- I guess I should have specified "science within academia".

            • melling 6 years ago

              It’s not a rule but an observation. We can certainly become more self-aware and change our behavior.

              Munger’s Psychology of human misjudgment, for instance, is enlightening: https://youtu.be/pqzcCfUglws

            • MikkoFinell 6 years ago

              > The quote is a riff on what Max Planck, himself an eminent scientist said on the subject:

              Yes I'm familiar with the quote and of course it was obvious that you were referencing it. What's funny is that you seem to believe the only reason I'd disagree with something you said is that I'm unaware that Planck said something similar. I'm unable to get a hold of Planck to discuss it with him, and thought I'd ask you about it since you're here promoting his ideas, but I realize that I should have made that clear to you.

        • wwwtyro 6 years ago

          That's a good point. We should probably murder any scientists once they reach about 50, so we can speed up progress.

          • logfromblammo 6 years ago

            And here I thought we only murdered scientists--or at least killed their careers--when they stopped publishing. "Publish or perish."

    • ben_w 6 years ago

      Give? Patents expire, then commercial pressure takes over. And if they try to keep it secret, someone else will replicate their work and the outcome is much the same.

      • jacquesm 6 years ago

        In a world with immortals immortals will end up holding the power and they will ensure they continue to hold on to that power. If patents are still a thing in a world like that you can expect such simple changes to legislation as 'patents expire with the death of the inventor', it seems to be good at first glance but in a world with immortals it means some patents will never expire further cementing their hold on power.

        Immortality will create a lot more problems than it will solve.

        • wwwtyro 6 years ago

          > Immortality

          No reasonable person is talking about immortality. The issue here is defeating the diseases of old age.

          > will create a lot more problems than it will solve.

          That's a massive unfounded claim you're holding up against saving the lives of a hundred thousand people per day.

        • ben_w 6 years ago

          Patents currently expire before any immortality products could be known to work correctly. So why would anyone change a rule like that?

          • jacquesm 6 years ago

            Even immortals need a living.

            • ben_w 6 years ago

              Doubtful (UBI) but also not an answer. Anti-geriatric treatment will be ignored until after their patents have expired because almost nobody will believe they work until 30 or 40 years after it becomes available.

        • MikkoFinell 6 years ago

          Your solution to the problem with patents is to kill everyone?

    • Symmetry 6 years ago

      The same reason scientists gave us cancer drugs, AIDS drugs, etc without us becoming their slaves?

jlebrech 6 years ago

I've reached my article limit so i'm going to die.

  • subcosmos 6 years ago

    Try becoming "born again" in an incognito tab?

Angostura 6 years ago

To save you a click, the Thing in question is the nucleolus, which manufacturers ribosomal RNA.

  • Spare_account 6 years ago

    And for those wondering (because I was) 'nucleolus' is not a typo, it is contained within the nucleus.

    • magduf 6 years ago

      I remembered just enough of my high school biology to (barely) remember the term nucleolus when I saw it here....

Density 6 years ago

The immortal boomer meme inches ever closer.

  • magduf 6 years ago

    First, Boomers will probably be mostly dead before all this anti-aging research can benefit them.

    Second, even if that's not the case, people are constantly getting killed off thanks to our addiction to the automobile (and in America, the gun). Eventually these Boomers are going to get knocked off. Maybe if we restrict guns and get better public transit the Boomers can live for centuries, but I don't foresee this; these changes are going to take centuries.

    Edit: "addiction", not "addition"

    • perl4ever 6 years ago

      I feel like I've read similar comments on HN about cars and guns over and over. Seems odd to be preoccupied with cars and guns when most people don't die of either. What about chainsaws and bathtubs? Cigarettes, trampolines, etc?

      Pneumonia, heart disease, stroke, COPD, pneumonia and lung cancer each kill more than cars in the first world.

      In the third world, top causes of death are HIV, pneumonia, heart disease, diarrhea, stroke, malaria, TB, COPD, and measles - cars don't even make the top ten.

      Source: https://en.wikipedia.org/wiki/List_of_causes_of_death_by_rat...

      • magduf 6 years ago

        >I feel like I've read similar comments on HN about cars and guns over and over. Seems odd to be preoccupied with cars and guns when most people don't die of either.

        Cars are the #1 killer for people less than middle-aged (where age-related diseases take over). 30,000 people a year die in the US alone from cars, and it's even worse in other countries.

        >Pneumonia, heart disease, stroke, COPD, pneumonia and lung cancer each kill more than cars in the first world.

        Only for old people. For young people, the ones who really matter more for the future of society and the economy, cars are easily the #1 killer.

        Here's a source: https://www.everydayhealth.com/kids-health/car-crashes-the-n...

        Guns are probably the #2 killer of children.

        • perl4ever 6 years ago

          I agree that cars and guns are common causes of mortality among groups that already have low overall mortality.

          It occurred to me to look up statistics adjusted by years of life lost, which gives more weight to younger victims and seems to favor your agenda.

          From https://en.wikipedia.org/wiki/Years_of_potential_life_lost

          "While the most common cause of death of young people aged 5 to 40 is injury and poisoning in the developed world, because relatively few young people die, the principal causes of lost years remain cardiovascular disease and cancer.[4]"

          [Regarding Australia:] "When disability adjusted life years are considered, cancer (25.1/1,000), cardiovascular disease (23.8/1,000), mental health issues (17.6/1,000), neurological disorders (15.7/1,000), chronic respiratory disease (9.4/1,000) and diabetes (7.2/1,000) are the main causes of good years of expected life lost to disease or premature death.[7]"