[HN Gopher] Turning back time with epigenetic clocks ___________________________________________________________________ Turning back time with epigenetic clocks Author : Brajeshwar Score : 134 points Date : 2022-01-29 14:32 UTC (8 hours ago) (HTM) web link (www.nature.com) (TXT) w3m dump (www.nature.com) | Metacelsus wrote: | Stem cell biologist here. Note that different cell types have | different epigenetics. Most of these studies are looking at white | blood cells. Effects on these cells may be different from | elsewhere (brain, muscle, etc.) | kkoncevicius wrote: | The epigenetic clock by one of the people quoted in the article | - S. Horvath, is notable for working across different tissues, | with a few exceptions like germ cells. | axg11 wrote: | I used to work in genomics. I think the quest to have a universal | epigenetic measure of ageing will end up in a dead end. | | Ageing is relative to a starting point and the variability | between people in terms of phenotype is huge. | | By way of analogy, would it be possible to come up with a | universal measure of ageing for cars? Cars are a complex system | made of thousands of components, each of which can age | differently over time. Each car make and model will age in a | different way. Some of the components even slightly improve in | performance over time as they "break in". | | The best way to measure epigenetic ageing is relative to a | starting point. There are few studies that follow the same people | over time (longitudinal) because it's difficult and expensive to | pull off. We'll eventually get there though. | jonmc12 wrote: | Any thoughts on the organ-based biological age score that Bryan | Johnson presents? More equivalent to monitoring all the | components of the car. | | I think these biological age scores are a really healthy way to | debate and create broader awareness about a) how our bodies | work and b) how we understand aging. | | https://blueprint.bryanjohnson.co/ | axg11 wrote: | Organ-specific is the most promising in my opinion. It's also | more likely to be actionable. Different organs will "peak" at | different ages. | amelius wrote: | Sounds like a task for data science. | kkoncevicius wrote: | Counterpoints: | | - The accuracy of current epigenetic clocks suggests it might | not be a dead-end with average error of 2-3 years, across | multiple tissues (and even Chimpanzees). | | - The variability of an aging phenotype is not that high. We | all loose bone density, loose teeth, hair turns white, memory | degrades, wrinkles appear, etc. In other words - aging follows | a pattern. | | - The car analogy assumes that aging is caused by damage over | time. But there is an alternative explanation: aging provides | and evolutionary advantage for a species and hence is | predetermined. | ikrenji wrote: | aging mostly happens after an organism reproduces, so there | is no evolutionary pressure to maintain fitness. there is no | pressure to develop maintenance mechanisms... | SuoDuanDao wrote: | There would be plenty of pressure to keep reproducing | indefinitely, just that then there might be too much | competition between ancestors and descendants for the same | resources. | echelon wrote: | > The variability of an aging phenotype is not that high. We | all loose bone density, loose teeth, hair turns white, memory | degrades, wrinkles appear, etc. | | People age at different rates depending on a wide variety of | factors. | | Progeria, over consumption of alcohol, too much stress, too | much radiation from sunlight, etc. | | The things you point to are measures of a biological age, not | a wall clock age. While they do correlate, they're not 1:1. | Some people age faster. | | > But there is an alternative explanation: aging provides and | evolutionary advantage for a species and hence is | predetermined. | | I don't buy this. We don't have a pre-programmed death. It's | rather that we haven't had any genetic pressure to live | beyond our current lifespan as it doesn't increase our | offspring's chances of success. | | There's little pressure from competing with children for | resources. Look at how many people there are in the world | today - the world supports billions of humans. There are far | greater pressures being exerted in other ways. | ridgeguy wrote: | From an evolutionary perspective, I think we can at least | say that absence of death doesn't confer a selective | advantage, else it would have appeared and radiated in | several billion years of biological evolution. | | It might even be that death provides selective | advantage(s), which would account for its being a nearly | universal feature of known life. A "pre-programmed death" | mechanism would be consistent with this. | kkoncevicius wrote: | I think we do have a pre-programmed death. Almost all | creatures die when they get older so in order to look for | evolutionary pressures we have to look across a long time | period and far back. For one - if organisms wouldn't die | evolution would not happen. Or at least the non-dying ones | would stay behind and be left living in environments they | are no longer suited for. For ancient creatures food and | resources might have been scarce and so it was advantageous | for non-evolving old members to die-off sooner. | | Also, whatever we think about these epigenetic clocks, | there are few things to come to terms with: 1) they work | across pretty much all individuals (and people with | progeria do exhibit older epigenetic age [1]) 2) they work | across pretty much all tissues. I don't see how this could | be explained through "damage over time". The way I see it | damage should be random and not lead to something so | predictable that we could use it to guess a persons | chronological age with 2.5 year accuracy. | | [1]: https://pubmed.ncbi.nlm.nih.gov/30048243/ | ddingus wrote: | I do too. | | Look at the tortoise. We know some that have lived two | centuries. They have their niche, do what they do, and | live a very long time. | | During their evolutionary journey to their current local | maxima, I wonder whether they lived shorter lives? | kgin wrote: | What are your views on the trial that reversed epigenetic age | in optic nerves, allowing them to regenerate? | https://www.nature.com/articles/s41586-020-2975-4 | axg11 wrote: | I think epigenetic age _does_ make sense for very specific | systems. For example, just focused on the optic nerve. Good | luck getting an optic nerve sample in a live human though! | cblconfederate wrote: | The reason for pursuing clocks is to use them to assess the | efficacy of longevity interventions. Currently, with an error | bar ~3 years they are not bad at all, and can be used to assess | aging relative to a starting point, as you suggest. | ericmcer wrote: | A thirteen year old having low bone density, heart problems and | degenerating joints would be strange, but for someone > 70 it's | almost expected. The car example is dumb because cars don't | have a built in mechanism for regeneration that is failing. Our | bodies mechanisms for self-regeneration weaken and then we see | all the symptoms of aging. | elromulous wrote: | You made good points, but maybe you could have done so | without calling the parent's analogy "dumb"? | monkeycantype wrote: | I believe we have a genetically determined lifespan. There is a | reason lifespan has been optimised to this duration. As we age we | accumulate viruses, mutations. The tissues that were positioned | and differentiated during development accumulate damage. From the | perspective of the species the only feasible way to get back to a | healthy state isn't to eradicate the viruses and repair the | tissues, its to jettison the withered husk and repeat the | development process with a fresh new body. I we 'reset the clock' | we're not removing the damage, the mutations, we're just | overclocking the body. If overclocking can get me another 20%, | I'll take it. Hell 3%, we'll take it. But what I want I really | want is the full factory refurb, with a little extra ram please. | pishpash wrote: | Many species can regenerate, especially plants. | f38zf5vdt wrote: | > In 2019, a small study raised the tantalizing prospect that | ageing could be reversed. Scientists in California gave 9 men | aged 51 to 65 a growth hormone and two diabetes medications for a | year. The drugs seemed to rejuvenate the men's thymus glands and | immune function. They also shaved 2.5 years off the men's | biological age, as measured by one of the most talked-about | technologies in ageing research: epigenetic clocks. | | It's also worth nothing that another study shaved "3.2 years" off | the "epigenetic clock" simply with lifestyle changes over 2 | months. [1] | | [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064200/ | mrfusion wrote: | Doesn't fasting and possibly IF radically raise hgh? | habitmelon wrote: | All these measures of biological age might be useful, but the | real test is just waiting and seeing how long people end up | living. | robbedpeter wrote: | Specifically, watch Bill Gates, Bezos, Branson, Thiel, and | Musk. They're first in line with all the influence and | resources needed, so if current life extension efforts pan out, | we should see it happen. | | If it happens soon, the Putin situation could get weird. | tagoregrtst wrote: | How so? Are you implying that the only way out of the current | West-East impasse is through the death of its leaders? | | This is not how it panned out in Cuba, China, North Korea, | Venezuela, etc. | robbedpeter wrote: | No - Putin is currently dictator for life. A more or less | immortal dictator would be an entirely novel, and truly | weird, situation on the world stage. | tagoregrtst wrote: | Is Putin popular with Russians? It seems like an | important consideration. | mythrwy wrote: | There would be a lot to stay current on to stay in power. | | How much information can a brain hold assuming it lives | forever? Does it run out of space at one point? | robbedpeter wrote: | It wouldn't be a limitation for centuries, or possibly | millenia. The brain very efficiently packs information, | and integrates with external storage. We'll be able to | digitally augment brains directly long before temporal | memory capacity becomes a problem. | tasty_freeze wrote: | Much of the information we collect has a half life, or | situations change and that information, while still | valid, is not applicable to the issues we are facing | currently. The vast majority of things we learn end up | getting discarded at some point. | | Think of the most recent book you read. How many of the | details actually stuck with you at the moment you closed | it. Now think of a book you read 10 years ago. How much | of that do you remember? | | I took years of mathematics and was able to do well on | tests, but 40 years later I only recall the "shape" of | PDE solutions and couldn't actually solve anything | anymore. Instead my brain is stuffed full of arcane | knowledge I need to do my job, and if I don't use it | within a year, I probably need to learn it all over | again. | robbedpeter wrote: | This is a valid question for different reasons, too. I | have a problem with the speech and behavior of immortal | characters in books - why would a 300 year old powerful | vampire behave like an immature emo teenager? | | There's a reason we associate wisdom with age. The more | times anyone of reasonable intelligence makes mistakes, | the more opportunities they have to learn, and their | behavior changes according to the degree to which they | take on the lessons of life. | | One big danger of immortal dictators is the simple fact | that they'll stop learning. Through wealth and power they | shield themselves from the consequences of mistakes, | getting themselves and their people stuck in a local | minima. | | Imagine immortal Mitch McConnell, ever increasingly | wealthy through passive income, maintaining power and | privilege for his constituents and thus his hold on a | senate seat. | | If life extension pans out, liberal societies will have | to impose term limits in a serious and well considered | way. Humans aren't ready for the existing pace of | technological development, and we're going to encounter | an exponentially increasing number of problems, like the | politics of immortality. The best thing we could do would | be to maximize freedom of expression and minimize the | duration of social institutions to achieve sufficient | maneuverability to adapt to modern life. | TeeMassive wrote: | I think a better question would be not how _long_ but how | _well_ people live their end of life. Most people would trade | living up to 90 fully aware and mostly active instead of up to | 100 in misery and dementia. | black_13 wrote: | JohnJamesRambo wrote: | I really wish they had a group that had the DHEA and metformin | without growth hormone. I can get those easily and cheaply on the | internet. I'd like to see how much of the effect they saw was | just those two. | jml78 wrote: | One of the issues with metformin is how many times it has | gotten recall for cancer causing contamination. Buying on the | internet, you are never going to get notified | DeWilde wrote: | Metformin is not ideal for some if not most men. It wipes out | testosterone levels. | | After a few weeks of taking it my T levels were below average | and free-T levels were that of 100 year old men. This was a | huge drop from the above average levels, for men in 20s, that I | usually have. | JohnJamesRambo wrote: | I've had the same experience. Feel like shit every time I get | hopped up on the latest paper and try it again. I don't want | to live forever with T levels of an old man. I thought maybe | I was the only one feeling this way, although I had seen the | papers about it lowering testosterone. | DeWilde wrote: | [0] might be relevant to you, seen other papers that I | found when I discovered this issue. From what I gathered | the reason for this is that metformin reduces blood | cholesterol levels which are important for testosterone | production. | | [0]: https://pubmed.ncbi.nlm.nih.gov/11707532/ | cantrevealname wrote: | > _Scientists in California gave 9 men aged 51 to 65 a growth | hormone and two diabetes medications for a year. The drugs seemed | to rejuvenate the men's thymus glands and immune function. They | also shaved 2.5 years off the men's biological age_ | | The study itself says: | | _During the first week of the trial, rhGH alone (0.015 mg /kg) | was administered to obtain an initial insulin response, and | during the second week, rhGH was combined with 50 mg DHEA to | evaluate insulin suppression by DHEA alone. During the third | week, the same doses of rhGH and DHEA were combined with 500 mg | metformin. Beginning at the fourth week, all doses were | individualized based on each volunteer's particular | responses._[1] | | So the meds in question are: | | - recombinant human growth hormone (rhGH) [2] | | - dehydroepiandrosterone (DHEA) [3] | | - metformin [4] | | If you wanted to have this treatment for yourself, how could you | proceed? I assume that it would be just about impossible to | convince your family doctor to prescribe this drug regimen for | you? If you were to do-it-yourself, what would be the best way? | It seems that metformin is widely available but I don't know | about the availability and cost of rhGH and DHEA. | | [1] https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028 | | [2] | https://en.wikipedia.org/wiki/Growth_hormone_therapy#Recombi... | | [3] https://en.wikipedia.org/wiki/Dehydroepiandrosterone | | [4] https://en.wikipedia.org/wiki/Metformin | bleachedsleet wrote: | AgelessRX will prescribe metformin [1], DHEA is legally OTC in | the US, and any kind of HGH is probably readily available at | your local gym (also a number of hormone doctors online will | prescribe it easily) | | [1] https://www.agelessrx.com/metformin | aaaaaaaaaaab wrote: | >I don't know about the availability and cost of rhGH and DHEA. | | DHEA: available over-the-counter in the US | | rhGH: go to your local gym and ask the biggest guy | hourislate wrote: | For a more thorough dive into this topic, Dr Brad Stanfield on | Youtube. I haven't found anyone better in breaking down the | latest scientific studies on Longevity. | | https://www.youtube.com/c/DrBradStanfield | | There is evidence that Metformin doesn't extend the life of | healthy people but does extend the life of Type II diabetics. | | https://www.youtube.com/watch?v=iByaqfmWfHQ | | I would also caution HGH for men since it can enlarge the | prostate gland. | | David Sinclair had mentioned in a podcast that we use to be | cold and hungry and now we're warm and fat all the time. Need | to be cold and hungry more often. | | https://www.youtube.com/channel/UCwD5YYkbYmN2iFHON9FyDXg | | Peter Attia has said that the number one thing he believes will | extend healthspan/lifespan (if you did nothing else) is | exercise. He wish he could prescribe as a medication. | | https://www.youtube.com/c/PeterAttiaMD | XzetaU8 wrote: | Michael Lustgarten Ph.D is another good source for biohacking | and longevity matters. he takes a diifferent approach though | since he's trying to reverse his epigenetic age specifically | through diet. | | [1] https://www.youtube.com/channel/UCT1UMLpZ_CrQ_8I431K0b-g | | [2] https://twitter.com/mike_lustgarten | telxosser wrote: | The most interesting thing I have heard from Sinclair is the | studies on mice that eating once a day was what extended | lifespan the most. Everything else was not that important | diet wise. | | It sounds like to me the method is eat once a day and get in | the best physical condition possible from working out. Beyond | that, I am just not going to stress about it. Surely, not | going to take any reverse risk with HGH or experimental | drugs. | wtetzner wrote: | So, exercise, fasting, and being cold? | AuryGlenz wrote: | There are peptides you can buy online that make you overproduce | HGH, though it's hard to say if the effects would be the same. | You can also easily buy metformin from Indian pharmacies. | staticassertion wrote: | First and foremost I would suggest doing research. A recent | study showed that in healthy individuals Metformin had no | impact on all-cause mortality and there are potential side | effects. | | Of course, doing research is hard. Because it isn't really | research in the sense of running a legitimate study, it's | research in the sense of studying the work of others as an | outsider. | | Personally, I like Dr Brad Stanfield. | https://www.youtube.com/c/DrBradStanfield | | He's not afraid to reverse positions, he's articulate, he calls | out when research is or is not compelling and explains why. | | Again, personally, I expect the number one thing you can do to | improve your healthspan is probably focus on what you can stop | putting in your body vs what things you can add. If you're 40+ | though, might be worth looking at other options. | sometimeshuman wrote: | Berberine is commonly promoted as a vitamin alternative to | Metformin. Even if Berberine also has no impact on all-cause | mortality (idk), I can anecdotally share that 500mg 30minutes | before lunch considerably lessens my post lunch fatigue. | | As for human growth hormone, this Huberman Labs podcast | advises against taking it but also offers many natural ways | you can boost it[0]. | | [0]https://www.youtube.com/watch?v=x7qbJeRxWGw | _0ffh wrote: | Funny to see metformin popping up again, it's already a staple | in the anti-aging movement. | ineedasername wrote: | _> unblinded study with no placebo control arm. "If you have nine | people," says Horvath, "and you get a statistically significant | result, it means there's a strong effect."_ | | Wow, no. Just... No. It doesn't. | | That is so wrong that, from a researcher with a doctorate in | biostatistics, it's very difficult not to infer deliberate | misinformation on their part. To give some benefit of the doubt | though, maybe it was just a very poor choice of words. | | Statistical significance with 9 samples is suggestive at best. It | just barely qualifies as a pilot study. | | They even say that significance means there's a large effect, | which again... No. | | Significance in small sample indicates practically nothing by | itself. What was the _actual_ effect size? Though even at 0.8, | with 9 samples I would be be very cautious in my optimistic. | SamoyedFurFluff wrote: | I wonder if, read charitably, the intent is to say with a | strong enough effect a small statistic size doesn't necessarily | mean useless. For example, if I removed the hearts from 9 | living people and they all died, I can conclude people need | their hearts to live. | ineedasername wrote: | Yes, I try to allow some benefit of the doubt in my comment, | but from a doctorate is statistics it's a bit harder to | excuse. | | He doesn't have to make an argument from logical implication, | there are perfectly good measures of effect size he could use | that would allow him to say something like "not only was this | statistically significant but it demonstrated a large effect | size as well." | | My hope is he said something like _" We not only saw a P | value of < 0.04 but a Cohen's D of 0.7."_ and then the | reporter was like, "yeah I'm gonna need you to dumb that down | for our readers" | naasking wrote: | > That is so wrong that, from a researcher with a doctorate in | biostatistics, it's very difficult not to infer deliberate | misinformation on their part. | | We don't really know the context for that statement. The | journalist could have easily misunderstood something and used | quoted him in a totally wrong context. | ineedasername wrote: | I can give him a little benefit of the doubt, but if he said | those specific words and it wasn't a misquote then it was an | extremely poor choice of words. Those words, in that order, | are so fundamentally wrong that I cannot imagine them being | correct even in additional surrounding context unless the | next few words that were cutoff were _"...as measured by | [insert preferred methodology for effect size] "_ that would | still be poor phrasing, implying that significance led to | effect size. | czbond wrote: | Also, a drug free option is intermittent water fasting for 6 | consecutive days a month. [Disclaimer: do your own research, | consult a doctor, blah blah] | cruelty2 wrote: | peteradio wrote: | 2 days per week I do a coffee and beer only fast. I can | guarantee no toxins survive the resulting torrent. I like to | know I'm starting the week with a totally blank slate. | NavinF wrote: | 6 days a month!? Even if an RCT comes out proving this works, | I'd prefer to die a little sooner rather than do that my whole | life lol | | The way I see it, you're burning something like (6/30)/2 = 10% | of your quality-adjusted life years. Fasting had better | increase lifespan by 7-8 years to be even close to worth it ___________________________________________________________________ (page generated 2022-01-29 23:00 UTC)