12 ms·
A primer on the current state of longevity research
- readthenotes1 2y agoLife is too short to spend time reading a essay that could have been condensed to: Nothing solid. Work in progress.
- falcor84 2y ago99% of proper good science is "Nothing solid. Work in progress.", it doesn't make it any less valuable. I prefer this honest and clear communication a hundred-fold over what comes out of universities' PR departments.
- black_13 2y ago[dead]
- wenc 2y agoFor the general public yes. But for researchers, it's super useful to know. I spent 2 years of my Ph.D. pursuing a dead-end research direction. If only someone would have told me, "yeah, we tried that and it didn't really work." This is why socializing at conferences is useful. Researchers will admit over a beer to stuff they tried but didn't work out and here's why. Because academia never publishes negative results, you'll never find that out by reading papers.
- ein0p 2y agoThat’s the tragedy of all research - very few negative results get published. For all I know most of the things I’m working on at the moment have been tried and discarded
- sdenton4 2y agoSo, I used to think this, but seeing a lot of success and failure in machine learning projects has taught me that negative results can be quite difficult to interpret. You typically don't know if it's because the underlying idea is flawed, something went wrong in the experiment setup, some bug went undetected in the code base, or whatever, we explored the wrong corner of the hyperparameter space, or whatever. It can also be the case that the idea is correct, but the effect is miniscule compared to other effects. Now, when a pile of groups try something and it doesn't work out for anyone, things start getting interesting... But if course it takes pretty open discussion to know when that's happening.
- ein0p 2y agoThere are, broadly speaking, two types of negative results. The most numerous one is when the researcher tried a thing but does not understand why the thing did not work. There are so many knobs that just from the plain combinatorial perspective these results are not very valuable - they carry next to no information unless someone else takes the effort to understand why the thing did not work. But there is another group of results, encountered quite often, where the researcher either knows why the thing did not work, or at least has a solid, plausible hypothesis. I wish this latter group was more socially acceptable to publish and valued by the community. It could still be that the person is "holding it wrong" even in this case, but still, it would be useful. The era when one could cheaply try something out because their training run completes overnight seems to be gone for good.
- sdenton4 2y agoYah, I think that's where the experience of how failure happens in machine learning projects is helpful. I've seen wrong explanations for root causes drag out for months and sometimes years, as we tried different attacks that just weren't working. ML experiments are often quite cheap, compared to things like clinical trials or field studies... So we can indulge in running another experiment to confirm or deny our hypothesis quite easily. Humans are extremely good at inventing explanations for things. When the world doesn't do what we expect, we then have a choice of whether to believe we had the wrong explanation or just got the experimental details wrong... And epistemic hubris is a hell of a drug.
- bjornsing 2y ago> Because academia never publishes negative results, you'll never find that out by reading papers. And someone should be prosecuted for it.
- joewhale 2y agotransparency is good
- readthenotes1 2y agoSo is brevity
- anon84873628 2y agoSurprised there is no mention of Bryan Johnson. Whatever you think of his methods, he has certainly done a lot to popularize longevity research in the last couple years. Also no mention of rapamycin and related research on immune modulating pathways.
- abhishaike 2y agosure but he hasn’t contributed much to the actual research itself, i agree that he’s done cultural contributions, but afaict he isn’t funding much rapamycin is something i left out yeah, just was something i was less interested in + believe in less. i really only covered sirtuins because its had such a large cultural impact through David Sinclair’s book on aging
- Teever 2y agoWhat drives your skepticism of rapamycin for anti-aging?
- criddell 2y ago> he hasn't contributed much to the actual research itself From what I've read, he's done quite a bit of this but it's been restricted to a population of one. If his healthspan hits 120, the experiment he's run has been successful, no? He's already 46 so we will have a result relatively soon (within 60-70 years).
- indoordin0saur 2y agoIn 20 or 30 years you can look and see if he's 99th percentile for his age along whatever metrics (mile run time, VO2 max, skin elasticity, etc.) and that will be an obvious sign of a successful experiment.
- Temporary_31337 2y agoStatistically it will not be a very useful scientific experiment - too many variables, too small sample size. Plus he will die a lot sooner from all the pills he is taking.
- Kalanos 2y agoThanks for the review. Surprised not to see any mention of interleukins and metformin. [Warning - metformin linked to birth defects] https://www.nature.com/articles/s41586-024-07701-9 https://www.nature.com/articles/s41586-024-07701-9 The more I learn about molecular biology/oncology, the more skeptical I am of longevity research. The pathways are usually broad hub genes that shouldn't be touched. E.g. Myc is an oncogene. As a rule of thumb, any time you see "reprogramming," be skeptical. Gene therapy for neurodegenerative diseases should not be considered longevity.
- abhishaike 2y agothanks for reading! i could’ve covered the metabolic/immune stuff in deeper depth…might make a part two for this all, i was pretty opinionated on what to add in, there is a lot more to the field
- api 2y agoLife extension in humans is difficult because we are already long lived for a high metabolism large mammal. That means evolution has probably already tweaked the obvious knobs. It doesn’t mean it can’t be done, just that it is not likely to be as easy as pushing a few chemical buttons or turning something on or off.
- kurthr 2y agoWhy would evolution "tweak the obvious knobs" for something well beyond our breeding age 100-500-5000 years ago? The best argument is that those same tweaks affect child bearing/survival performance in the same direction. Since sickle cell and other diseases were selected for, it seems unlikely all of them go the same way.
- marcus_holmes 2y agoThis. If anything, evolution would seem to select for lower longevity so more breeding sooner (assuming that if we live longer we would put off breeding until later, which may not be true, and if it is, is probably only true with contraception). And, of course, the oft-repeated "anything that happens after reproduction is irrelevant to evolution". Which isn't 100% true (it takes a village to raise a child, after all).
- reasonattlm 2y agoIt is hard to cover everything related to longevity, given that there is a vast diversity of approaches, and a lot of work presently taking place. https://www.agingbiotech.info https://www.agingbiotech.info shows how much work goes into just making lists for just the industry side of the house. Read a few of the lengthy end of year posts at Fight Aging! to see just how much there is to comment on (e.g. https://www.fightaging.org/archives/2023/12/a-look-back-at-2023-progress-towards-the-treatment-of-aging-as-a-medical-condition/ https://www.fightaging.org/archives/2023/12/a-look-back-at-2... ), and Fight Aging! only covers an opinionated selection of the full spectrum of research and development.
- alphanumeric0 2y agoSounds like the future is bright for the field and that it has lots of applications. I'd imagine future aging treatments would employ several of these methods together, say cell reprogramming for your organs, along with resetting some of those aging biomarkers. It's funny that it was considered a pseudoscience for such a long time, when there's lot of clinical applications outside of trying to live longer. For me, as someone with celiac disease, I know the age of my intestines are probably older than most people, after constant damage from gluten. It'd be nice to have a cell reprogramming treatment for intestines.
- shiroiushi 2y agoThat would be nice, and for other things too, but wouldn't it theoretically be simpler to grow cloned organs and other body parts and surgically replace your old ones with those? (Obviously, there's real technological hurdles to growing cloned organs, but these seem somewhat easier than the hurdles for reprogramming your cells.)
- rob74 2y agoMight be difficult for the brain, and a very significant amount of the elderly have brain problems (Alzheimer's and other forms of dementia)...
- adrianN 2y agoIt seems difficult to replace bones, cartilage, muscles and skin.
- shiroiushi 2y agoHow so? Surgeons do it all the time. You've heard of skin grafts, right? You can remove patches of skin and replace them with other patches of skin from the same person and it'll work fine, aside from scarring at the sutures of course. A common problem is not having enough skin to work with of course (it's not like people have lots of spare skin), but if someone got severe burns for instance and we could grow cloned skin for them to implant, that's far preferable to current techniques. Of course, replacing anything has issues with 1) the trauma of surgery itself, and 2) scarring where things are cut and spliced, but this is better than not replacing things at all and just dying or getting an amputation or whatever. Of course, if you could just get an injection that programs your body to fix these things itself, that's better, but my whole point is that it seems to me that growing cloned organs is closer to our current technological capability.
- oldpersonintx 2y ago[dead]
- sriram_malhar 2y agoNice review. But I get the ick. As with AI/ML research, it has tremendous political, social, economic, environmental consequences. As AI/ML has shown, the pace of development and availability has outpaced humans' ability to think through the consequences until they have already happened and are in the hands of very powerful techbros and oligarchs. I have no appreciation of Hinton and other leaders' change of heart about the catastrophic consequences of their research. A PhD in Longevity research, should be evaluated for its philosophical deliberations as much as it pokes the edge of the state of art.
- xvector 2y agoDeath is a tragedy. I see zero issue with longevity research. Any second-order societal effects can be dealt with, but this is absolutely not an area where we need regulations and deliberation of "safety" when literally everyone you know, your children, and your loved ones will die without this research. The problem of dying is a much more urgent problem than, say, overpopulation or duration of power. Those can be solved once we aren't all, well, dying.
- Daniel_sk 2y agoDeath is by design and is a vital part of evolution. I don't have issues with trying to make our human lives a bit longer (and preserving same quality of life), but achieving biological immortality would open a lot more problems.
- deleted 2y ago[deleted]
- dsign 2y agoDoes anybody know of any longevity research on bacteria? If we can put together Boeings and LLMs, we can probably put together computational models of longevity for living beings... even if it's just for Mycoplasma genitalium. But I have never heard of one.
- pfdietz 2y agoWhat does longevity of an organism that reproduces by binary fission even mean?
- dsign 2y agoWhat happens if you abort the binary fission? If the answer is "you shouldn't", please tell me why. My argument for why we should is that some people want to scientifically know if it is possible to artificially, arbitrarily extend the lifespan of an organism. What are the constraints? What are the possibilities? What is the cost? Can we use GPUs?
- pfdietz 2y agoHow completely nonresponsive to my question.
- treprinum 2y agoBoeing is a few orders of magnitude simpler than a single human cell. We can't even create a CFD model of an airplane that is realistic as can be seen on all airplanes or even race cars designed purely by CFD.
- causi 2y agoI don't know why but tech industry folks tend to be very resistant to the stupendous complexity of biological systems. The way biology builds functionality into structure can result in incredible space efficiency. Like neurons, for example. People assume the computational aspect of a neuron is only a tiny part of the structure of a neuron, when we have no reason to believe that. That is to say, people think you can equal its ability with a model many orders of magnitude less complex than a neuron. They don't want to think about the implications of that assumption being wrong. I always find myself coming back to the dragonfly brain. A dragonfly brain needs exactly sixteen neurons to take input from the 30,000 ommatidia in its eyes, use that information to plot the three-dimensional flight path of airborne prey, compute an intercept course, and send those signals to the wing muscles. How many transistors do we need for that? Input from 30,000 camera pixels, tracking moving objects in 3D space, computing vectors. Now you have a neuron to transistor efficiency ratio. Now multiply that by 86 billion. One brain. AGI's gonna take a hot minute, folks.
- sorokod 2y agoDon't know the average age of partipants here but I assume it is low enough to explain the focus on longevity rather then on the quality of life. If you get a chance to interview a person in their late 80s, ask if they would welcome a life extension of say, 20 years.
- Gettingolderev 2y ago[dead]
- lifefeed 2y agoI've known two people to reach their 90s, and they were/are both happy for it. But one was very physically active, and one is wealthy enough to afford round-the-clock in-home care. I imagine for the middle class and infirm, reaching your 90s could be hell.
- Tade0 2y agoMy maternal grandparents are in their mid to late 90s and it's indeed not glamorous. Fortunately they've retained mobility, partly thanks to living four floors up without an elevator for 75+ years. As a side note in their block people passed away starting with those who lived closer to the ground. Not everyone is this fortunate though, as grandpa's older sister is 100 and bedridden.
- ben_w 2y agoWhat you're describing has been known since the ancient Greeks made stories about Tithonus. The reality is, current research mainly exists as "old age illness is expensive, can we prevent all those things going wrong by slowing down aging?" (Currently: yes, with multiple different approaches, but so far only in lab animals).
- sorokod 2y agoThe Greek mythology is deeply plugged into the human condition. I didn't know the Tithonus story, my comment comes from personal experience.
- Jeff_Brown 2y agoLongevity research is likely to improve quality of life too. Diseases that have been tackled separately since forever -- cancer, Alzheimer's, diabetes -- are starting to be seen as manifestations of a single underlying process, which is what we aim to stop.
- lm28469 2y ago> are starting to be seen as manifestations of a single underlying process Eating and breathing pollutants ?
- lawlessone 2y agoI'm not an expert in any of this, but from reading this stuff a long time it almost always goes back to inflammation.
- Temporary_31337 2y agoInflammation is still a symptom- body reacting to something that it doesn’t like so it’s like saying that almost every smoke goes back to fire. Not wrong, not horribly useful.
- rowanG077 2y agoNo that isn't it. Else all animals would have at least similar life spans. A dog doesn't die at 8 from cancer because of eating and breathing pollutants. And neither does a human at 80. The only thing most pollutants do is make it worse. The underlying cause is our body not being able to maintain itself over even short timescales, with or without pollutants.
- digging 2y agoAll animals have different responses to toxins, pollutants, cancer growth, etc. We're kind of actually at a "sweet spot" for cancer rates, big enough to get a lot of cancer, not so big that we need extraordinary cancer resistance like whales.
- davidelettieri 2y agoShould diet / exercise be the primary mechanisms to support longevity? https://gero.usc.edu/2022/04/28/valter-longo-longevity-diet/ https://gero.usc.edu/2022/04/28/valter-longo-longevity-diet/ edit: also this is quite interesting https://www.bbc.co.uk/programmes/b01lxyzc https://www.bbc.co.uk/programmes/b01lxyzc
- drillsteps5 2y agoI'm (somewhat) surprised to not see DeGray or his SENS mentioned in the article or the discussion. I thought he and his approach gradually moved from the area of crazy science to (at least) one of the approaches attracting attention from some more mainstream researchers? After all the "Hallmarks of Aging" (2013), more or less mainstream research article published in "Cell", looked at the aging process from a similar perspective. If I understand correctly, at least one of SENS components - namely, AmyloSENS - is currently being targeted by a number of biotech startups, looking into use of senolytic drugs to clear up senescent cells. DeGray himself is currently attempting a Robust Mouse Rejuvenation however from what I understand the results from trial 1 were more than modest, if not to say disappointing.