9 ms·
Review of Anti-Aging Drugs
- metalman 1y agoI am very certain that framing ageing as a disease that can be treated with a drug is a false oversimplication that can not yield meaningfull results. Personaly I love complexity and trying to parse all of the moving peices in a problem, but ageing involves an unknown total number of peieces, and what we do know is daunting, many of the biological processes operate within tollerances of parts per billion, and the large number of processes effect each other. The worst part of "anti ageing" is that it completly ignores the reality of lifestyle inputs demonstrably having accelerated ageing effects. cart, horse
- cj 1y agoFrom the conclusion paragraph: > Your primary life extension program is diet and exercise. Choose a diet that works for you. Stay slim. Considering heart disease is the #1 killer, doing whatever you can to not die from heart disease is the best place for most people to start. Even in 2025, diet and exercise are still king.
- adamgordonbell 1y agoAlso this: > The best reason to take multiple life extension supplements is to hedge our bets, because we really don’t know which of them are effective in humans. And earlier: > Personally, I take large doses of rapamycin 2 days a week, 8 weeks per year. For personalized recommendations, you can consult your favorite life extension doc.
- cactusplant7374 1y agoRapamycin modulates the immune system. I get that he's probably consulting a doctor but can you imagine taking this risk during a pandemic or even in older age? It makes me uncomfortable to play around with these very powerful drugs.
- jordanb 1y agoThese roads people go down always arrive at eating collidal silver...
- MarcelOlsz 1y agoGet with the times, methylene blue is the new it girl.
- malfist 1y agoAs a party trick, it'll make people pee blue. But don't do this, it isn't safe. Especially without consent
- YZF 1y agoThe dosage for longevity is supposed to be low enough that this risk is minimized. Lots of things you do modulate your immune system (including e.g. exercise). It's a risk/reward thing, every time you get into your car you're also taking a longevity risk. I think there are some proper human trials happening but the jury is still out.
- cactusplant7374 1y ago> I think there are some proper human trials happening but the jury is still out. That's exactly my point. No one really knows the risk that they are taking.
- rscho 1y agoHow to hedge a bet 101: 1.you bet on risky stuff using something of value (money, health,...) 2.since you're unsure whether your bet will pay off, you bet some more on some other risky stuff, just to be sure. BTW if you were wondering, of course all those proposed weird life-prolonging treatments are totally devoid of side-effects.
- malfist 1y agoOh there's plenty of people selling "side effect free" life extension supplements. But there's another name for side effect free medication: effect free.
- BobaFloutist 1y agoNever put 100% of your savings into a single slot machine. Take 10% of your savings to 10 different casinos and distribute them to 10 slot machines in each, in order to hedge.
- obloid 1y agoI recently saw a patient with overwhelming MRSA sepsis with multiple foci of infection including epidural abscess (around the spinal cord), and meningitis. This person was taking rapamycin presumably for "life extension" purposes. Almost certainly the immunosuppression from the rapamycin made the infection much worse. I'd be very wary of taking an immunosuppressive drug as an otherwise healthy person for theoretical life extension properties.
- loeg 1y agoAnd if diet alone isn't getting you to a healthy weight, the GLP-1 drugs are miraculously effective and don't have a lot of downsides aside from cost.
- FollowingTheDao 1y agoIs way too early to know about any downsides of these drugs. I’m afraid too many people are gonna find out the downsides when it’s too late.
- haar 1y agoI think for myself, regardless of what the downsides are - the likely alternative was death, which is still an option.
- malfist 1y agoThese drugs have been around since 2005. Exenatide was approved by the FDA for use in 2005. We've had plenty of time. Only their approval for weight loss is new
- FollowingTheDao 1y agoExenatide was a very small population base. The approval for weight loss means this drug is being taken by millions of more people which leads to a larger sample size. The larger the sample size the more negative effects will be revealed. I’ll just leave this here for the future m. I have no evidence other than common sense that it is ridiculous to think that injecting a hormone randomly in your body does not lead to side effects. Besides, who is going to be the one that links thyroid cancers and pancreatic cancers to these drugs? My father died of pancreatic cancer, no one really thought to ask why.
- daedrdev 1y agoThe majority is gaining literal years of healthy lifespan. It would take a lot of damage to even approach this gain for the average person. Like we used to do very invasive and impactful gastric surgery to try and get weight loss and nobody batted an eye, no?
- cm2012 1y agoYour overall mortality is actually best when you are overweight but not obese. Life expectancy at overweight bmi > standard bmi > obese bmi > underweight bmi. A few extra pounds when you are older helps you survive illness. The data is really really clear and replicated on this.
- derektank 1y agoThis only really holds for older people, who have basically no ability to recover lost muscle mass after a serious illness which makes it difficult them to continue to exercise.
- nahikoa 1y agoThe correlation is unambigous. The causation is a different story, e.g. illnesses often cause weight loss.
- standardUser 1y agoWhich segments of these populations have high BMI because of muscle mass instead of excess body fat? Which segments have low BMI due to childhood malnourishment or current or chronic illness? These are just some of the very obvious questions that have already been used to relegate your conveniently concise "fact" to "interesting, but not instructive".
- Aurornis 1y ago> A few extra pounds when you are older helps you survive illness. This doesn’t mean being slightly overweight from age 20 through 60 is an advantage.
- untrust 1y agoAnd sleep
- Animats 1y agoWinner, "Ascorbic". Do they mean Vitamin C?
- YZF 1y agoThe text says yes. Also the text says other studies supposedly shown decrease in lifespan in humans: "but the conclusion of this study was that supplementation with vitamin C depressed lifespan, probably by inhibiting production of the body’s native antioxidants, including glutathione and SOD=superoxide dismutase."
- chasil 1y agoMy physician has just advised that I eat a piece of fruit every day, and I try to do so. I think that is a safe way to ensure this bioavailability. I have tested low on vitamin D and my physician advised supplements. I see that vitamin E is also on the list. What natural foods provide those?
- ivape 1y agoWould any of the OTC stuff even be effective? Melatonin, NAC, and Berberine.
- frodo8sam 1y agoMelatonin is just for jetlag/otherwise shifted sleeping schedule, are people using it as an anti aging drug?
- chasil 1y agoMelatonin is always made from serotonin. Serotonin is made from tryptophan, which can also be made into niacin. Taking tryptophan and niacin as a supplement will boost both serotonin and melatonin naturally, assuming these pathways are working properly. However, this can be dangerous in the presence of an SSRI.
- YZF 1y agoA good place to read more about these: https://examine.com/supplements/n-acetylcysteine/?show_conditions=true https://examine.com/supplements/n-acetylcysteine/?show_condi...
- rscho 1y agoTruth be told, none of either prescription or OTC stuff has any solid research backing it. Some people, especially on HN are obsessed with living long and are always prompt to try the weirdest experimental stuff. Reasonable people should remember what the COVID period was on this website, and act accordingly...
- p_ing 1y agoIf you want to live long, be bipolar and take lithium. https://pmc.ncbi.nlm.nih.gov/articles/PMC7553080 https://pmc.ncbi.nlm.nih.gov/articles/PMC7553080 (no don't, it's hell on earth)
- unit149 1y ago[dead]
- pama 1y agoBe careful when reading such blogs: > Note that the dosage in the mouse experiments is quite high — 0.1% of the body weight every day, meaning about 2 ounces a day for me (70 kg). Mouse and human metabolism are very different. A better starting estimate would be 5g/day, not 57g/day. I hope people dont accidentally overdose themselves because of lack of a pharmacology background.
- rscho 1y agoLack of pharmacology background doesn't seem like the biggest issue when extrapolating from mouse to human.
- andoando 1y agoI just learned this the other day, but its called allometric scaling. Definitely far off linear.
- A_D_E_P_T 1y agolol, that one was really a howler. You're spot on. But for the rest of the forum: The most commonly accepted mouse-to-human conversion is: (D)*(3/37) = H Where D = the mouse dose in mg/kg. H = human dose in mg/kg. So if a 25g mouse eats 0.1% of its bodyweight in taurine, that comes out to 1000mg/kg. It translates to 81mg/kg for a human. If you weigh 100kg, an equivalent daily dose for you is 8.1 grams/day. The rat equation is similar, but 6/37 rather than 3/37.
- avarun 1y agoIn plain English: scale by body weight then divide by 12.
- Aurornis 1y agoScaling mouse doses to human by body weight is a common rookie mistake. A better estimate for dose scaling uses body surface area. Even with that, inter-species differences don’t allow prevent extrapolation. Scaling by body weight leads to the common mistake of dismissing mouse studies because the casual observer does the match (by weight) and thinks the dose used was excessive. It’s such a basic topic in medicine and scientific research that I don’t trust anyone who scales by body weight.
- catigula 1y agoA lot of people in the comments are talking about the "problem" of death and approaches to take, but really, the only thing you can do is philosophically make your peace. Anything else at this point is yelling into infinity.
- iammjm 1y agoThere is a difference between dying at 40 and dying at 80. Also, I see no reason why people couldn't live for, say, 200 years or even indefinitely. I think it is an engineering problem that can be solved and I wish we as humanity allocated more attention and resources into solving this particular problem. Especially as it concerns all of us. Solving suffering and then solving mortality sounds like a good project to me.
- catigula 1y agoPhilosophically there is no difference. The gun to your head is infinity, 40 years has no meaning.
- wan23 1y agoIf life's a game where you try to get the best score you can, more years gives you more chances to rack up points. Philosophically* there's nothing more important, and therefore nothing has more meaning than this. * different people can have different philosophies on life
- bluGill 1y agoRealistically you can maybe get another couple year from what I can tell. Is it worth it? I'd focus more on qulalitiy of your life. not everyone will die of something all these can help with, the obese person I used to know enjoyed eating - and we can now say in hindsight that diet changes would not have helped him live longer.
- lurking_swe 1y agoleading a healthy active lifestyle DOES improve the quality of your life. Getting diabetes and injecting yourself daily with insulin is not a quality life. Having trouble walking or playing with your grandkids because one is too fat and has ruined their joints is also not quality. Having a miserable last 10-20 years of life due to a stroke is also not quality. These things don’t mysteriously happen. :) Being able to take care of yourself into old age is the biggest gift you can give yourself. Why? It reduces your suffering as much as possible. But nothing is guaranteed of course. Personal story time…growing up my parents barely valued their health. Mom and dad were fat for years. My dad had a stroke at 65 and he’s struggling with symptoms 10 years later. My mom got seriously ill at 60 from years of mismanaged diabetes, and was in and out of the hospital for 3 years before dying of a heart attack. She ate a lot of cookies though - quality life achieved? In contrast my in laws walk 10k+ steps daily, eat healthy, and exercise. They’ve been doing it for years. They are almost 70, travel all the time, and keep up with their grand kids no problem! They themselves are doing better than their parents, who suffered from early onset dementia and high blood pressure. Just my opinions as someone that’s seen 2 very different approaches to “living”. I try not to obsess over it, but i certainly make sure my BMI is low and make sure my blood sugar is excellent. I’ll do anything to avoid going through what my parents did. I plan to enjoy my 60s and 70s!
- bob1029 1y ago> Fast for short intervals regularly, and longer fasts as they feel good to you. You can effectively do this every day if you just eat once per day. When I was properly obese, this technique resulted in rapid weight loss. Zero exercise was required to see results, which was good at the time because the not eating part was about all I could handle. Being in a fasted state is as close as you can get to actually reversing aging. Your body engages in a process called autophagy when nutrient-sensing pathways are down-regulated. When you are stuffing your face constantly (i.e., every ~8 hours), there is less opportunity for this mechanism to do its job. https://en.wikipedia.org/wiki/Autophagy https://en.wikipedia.org/wiki/Autophagy
- Eldt 1y agoDo you get acid reflux?
- gautamcgoel 1y agoSimple solution: take an antacid, like Tums.
- rscho 1y agoWhich happily, is totally devoid of side effects.
- sigmoid10 1y agoWhile autophagy does correlate with fasting and some studies link it to health markers, it should be noted that it usually takes at least 18 hours of continued fasting to even start and only goes into full swing after 48 to 72 hours. It is also an extreme cell response that is associated with high levels of cellular stress, which might have understudied long term detrimental effects. A simple calorie reduction either by eating fewer highly processed meals or regular intense exercise is much more universally accepted as longevity boosting, because it combats overweight, which is by far the most common disease that shortens general lifespan in the western world. There's really no good reason to force your body through these extreme diets. Don't be overweight, don't smoke, don't drink alcohol, maybe go easy on junk food and maybe do some exercise. And get your regular medical check-ups. Then you're already at the pinnacle of clinical longevity science. There is no actual anti aging drug yet that has a proven effect on humans. Best we have are some moderately promising monkey and small mammal studies, but they generally don't translate well.
- cyb0rg1 1y ago[flagged]
- rscho 1y agoYou've got horrible taste in cocktails.
- standardUser 1y agoVodka Red Bull is not a cocktail it is a drug.
- rscho 1y agoYou're absolutely right! This man's got horrible taste in drugs.
- derektank 1y agoSome of us don't get invited to those kinds of parties
- _zagj 1y agoRichard Miller's Intervention Testing Program should really be your go-to for this: https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions https://www.nia.nih.gov/research/dab/interventions-testing-p... He has no conflicts of interests, works for the NIA, and he's quite open to trying other compounds, having put out the call for suggestions.
- starchild3001 1y agoThis is a great discussion on longevity, though the main article focuses heavily on mouse studies. To add to that, I've been thinking about a framework that prioritizes the existing human evidence. My take, which I wrote about in the linked post, is to use a tiered approach: 1. Top Priority (Human RCTs): Start with what we know works in human randomized trials. This is our most solid ground and includes sustained weight loss, lowering LDL (especially with statins), intensive blood-pressure control, "polypill" strategies, and appropriate TRT for men with a confirmed deficiency. Also in this tier are things with more modest but proven benefits, like flu shots, multivitamins, and specific fish oils. 2. Second Priority (Strong Correlation): Look at interventions with strong positive associations in human studies and/or robust lifespan benefits in mice. This is where things like exercise, Mediterranean diets, social well being, coffee, green tea, fiber, and garlic fit in. 3. Third Priority (Emerging Science): Finally, consider the more experimental options that have shown promise in mice but only have early human signals. This is a long list, including rapamycin, calorie restriction, glycine+NAC, taurine, acarbose, metformin, and NAD+ boosters. Throughout this process, the goal should be to treat existing medical issues, track what works for you personally (N=1), and always consult with your doctor. Things that are still purely theoretical should wait for better data. Here's the full post with more detail: http://mylongevityjourney.blogspot.com/2022/08/a-short-summary-of-antiaging.html http://mylongevityjourney.blogspot.com/2022/08/a-short-summa...
- Aurornis 1y ago> appropriate TRT for men with low T You lost me here since this doesn’t appear in the linked article at all. You seem to be speaking about your own link, not the linked article on Hacker News. Be especially careful with TRT advice on the internet or from local clinics that push TRT treatments. The definition of “low testosterone” used in the longevity studies is very different than the definition used by TRT clinics looking to grow their customer base. There was an alarming study recently that showed a high percentage of men on TRT didn’t even have baseline testosterone bloodwork showing a deficiency. The clinics “diagnosed” them based on vague symptoms or questions, which is how they get around the fact that most men seeking TRT are not clinically deficient these days. Taking TRT will suppress natural production of testosterone and can lead to a lifetime need for TRT. Inappropriate dosing (which is common at the TRT clinics who want their customers to feel something early on) can also be net harmful and lead to cardiac complications or even psychiatric side effects like anxiety. TRT should be a last resort for people with true clinical deficiencies after eliminating the typical contributing factors (alcohol, sleep, obesity, etc). It’s not appropriate to mix into a list of supplements to take because it’s on the short list of medicines that can make you permanently dependent by causing testicular atrophy. This isn’t a concern in patients who already have testicular damage leading to hypogonadism, but it should be a huge concern for the average guy walking into a TRT clinic because they heard it was going to give them an edge or help in the gym.
- ontigola 1y ago[dead]
- Aurornis 1y agoThese articles really need a lot of context to parse as they paint some of the compounds as having potential upside without downsides. Metformin is amazing in people with diabetes, but among non-diabetics taking it for vague life extension claims it’s often discontinued due to side effects. Rapamycin has fallen out of favor among many in this space because they felt it was producing net negative effects as well as causing very annoying side effects like blisters in the mouth. I’ve followed supplement and fitness forums for years. It’s amazing how frequently a prescription medication will be held up as a wonder drug, but then people who try it discover it isn’t helping them or is even causing other problems they didn’t think about. EDIT: There are some serious scientific errors in this blog (dose conversions from mice studies). After clicking around the author appears to be into some quackery and conspiracy theory stuff as well. I flagged this submission because it’s not as scientific of a source as it claims.
- nutribueno 1y agoI'm surprised at the lack of intersectional shitposting when it comes to this subject, something along the lines of "FAANG intern tech bros making $1.5m TC are microdosing on ivermectin for health benefits." Get Wired or some other shit rag (the Altnatic?) to run with it complete with fancy full-viewport animations and gushing narrative intro over how it all started when someone's pitbull decided to take a shit in jeff bezos office.
- balamatom 1y agoUnderappreciated comment.
- the__alchemist 1y agoWhat side effects cause people taking Metformin to discontinue it? I'm taking, but haven't noticed any, but... you don't notice your baseline, I suppose!
- rscho 1y agoMetabolic acidosis. Not trivial at all.
- hn_throwaway_99 1y agoI thought this was an informative post, but for many of these compounds the simple "life extension" metric is the one that is least interesting to me. I have no problem dying in my 80s or 90s, but I just want to ensure that as much as possible that I have a solid mind and body right up until I die. For example, my father has been taking metformin for nearly 30 years after surviving a heart attack in his 50s (he has type 2 diabetes). He's now in his mid 80s and has basically no significant cognitive decline, despite that his father and both of his brothers had severe dementia when they died. Obviously this is just one anecdote and I'm not arguing anything about the specifics of metformin, I'm just saying that the fact he is able to enjoy such an active life in his 80s is the biggest gift - if he died tomorrow I think he and all of his family would just be so grateful at the vibrant life he had. Heck, for me I'd be fine with a drug that slightly reduced my lifespan if it gave me better quality of life up until the end.
- malfist 1y agoDiet and exercise are well know for the effect you're looking for. Its just not easy
- alkyon 1y agoAscorbic is not a correct name of a compound. Should be 'ascorbic acid' or Vitamin C. Such sloppiness cast doubt on accuracy of the whole review.
- malfist 1y agoI mean this guy is not a scientist. He's an enthusiasts aping scientific process. Look at how he talks about the "10-20% flexibility". Hypothesis assumed true, no supporting evidence. Same with his idea of being young longer. No evidence supports this, yet his comments proceed as if it's a gospel truth
- wlonkly 1y agoAgreed, I would have appreciated this more as a peer-reviewed meta-analysis than a blog post.
- oskarkk 1y agoFirst time I hear about him, but it looks like he is a scientist: https://www.researchgate.net/profile/Josh-Mitteldorf https://www.researchgate.net/profile/Josh-Mitteldorf > Look at how he talks about the "10-20% flexibility". Hypothesis assumed true, no supporting evidence. He started that part with "Here’s my perspective:", so for me it sounded more like his personal opinion/hypothesis, not a scientific consensus (and that hypothesis wasn't the topic of the article, so it's not strange for me that he gave no evidence for it there).
- malfist 1y agoThat makes this even worse, he should know better. I took a look at his publications and they're nuts. He's actually published claiming that covid vaccinations increase the spread of covid.
- pretzellogician 1y agoRead a little further... it's specifically called ascorbic acid and vitamin C. He probably just wanted to save space within the table.
- deadbabe 1y agoHow many people can really even afford life extension? As in living all the way into 90s or 100? Your retirement savings have to be pretty solid to enjoy those extra years. It’s not like before, the game has changed.
- lumost 1y agoIf 100 year olds were truly healthy, then I strongly suspect we'd see a shift in societal structure and expectations for retirement. Societies tolerances for a permanent upper class of retirees and a permanent lower class of workers would likely not last - worker's would likely be unwilling to do the same job for a century.
- Legend2440 1y agoIf people started to live longer, they would (hopefully) be in better health longer, and retire at a later age.
- lokrian 1y agoA better question might be can we afford NOT to have life extension? Advanced economies all over the world are filling up with sick, elderly people who form a massive drain on the economy, and it's going to get much worse. Developing medical technologies that can keep them healthier and productive for longer is the one thing that can save us here.
- IceHegel 1y agoThere's a fascinating tension with anti-aging drugs, which is that your preference would obviously be to take them as early as possible, so you spend more time at a younger age as opposed to just prolonging the last years of your life, where you'll be stuck in a nursing home anyway. But taking experimental drugs while you're young is also much higher risk, and you might see people sacrificing their 20s for the sake of their 70s in a way they end up regretting, even if there aren't any side effects.
- florbnit 1y agoThere's also a fascinating tension with physical exercise, which is that your preference would obviously be do it as early as possible, so you spend more time at a younger age as opposed to just prolonging the last years of your life, where you'll be stuck in a nursing home anyway. But doing exercise while you're young is also much higher risk, and you might see people sacrificing their 20s for the sake of their 70s in a way they end up regretting, even if there aren't any injuries. That said, even with risk of injuries it feels like a no brainer to be active and to be active from an early age. Also I don’t think people should wait until their late 50ies to make sure they get enough vitamin c to “avoid sacrificing their 20ies”
- lumost 1y agoIf we really manage to crack the code on aging, How certain are we that it's merely something to be delayed? Apparent age is at least somewhat reversible via lifestyle factors e.g. diet/exercise/sobriety.
- DennisP 1y agoIn fact that's Aubrey de Grey's approach: rather than trying to figure out all the complicated processes involved in causing the damage in the first place, so you can slow them down, just directly fix the damage afterwards. There's been quite a bit of research on this.
- cma 1y agode Grey is not using sobriety as a lifestyle factor to reverse anything I'm pretty sure.
- schappim 1y agoWhat's striking about "anti-ageing" research is how it keeps circling back to the same boring truths: don’t smoke, keep your weight down, move often, sleep properly, keep blood pressure and cholesterol in check, and go easy on the booze. If something makes an overweight, sedentary smoker hit 100, then it’s a miracle drug. Please let me know if/when you've seen that drug...
- echelon 1y agoGLP-1s are the first hint of that.
- schappim 1y agoYou’re right. I can’t think of anything else with that level of impact. Maybe we're all just taking things like statins or blood pressure drugs for granted, but I don’t think those have much effect on people who are already healthy...
- AntiqueFig 1y ago> don’t smoke, keep your weight down, move often, sleep properly, keep blood pressure and cholesterol in check, and go easy on the booze. And UVs, don't forget UVs.
- schappim 1y agoAs in UV light?
- clickety_clack 1y agoMaybe it’s the clockwork orange protocol: lots of milk and Ultra Violence.
- lokrian 1y agoThis is just another way of saying there have been no big advances in clinical anti-ageing. And that's probably because little serious effort is going into it, compared with say, military spending.
- FollowingTheDao 1y agoThis is useless. It takes zero account of genetic variability. I can tell you several of those things on that list that will decrease my lifespan. If you care about your personal lifespan, you should care about your personal genetics and your personal heritage. This was the same stupidity we saw with the blue zones. They didn’t think for a minute that these people lived for a long time because they were eating the foods they grew up on for generations.
- BobaFloutist 1y agoActually, those people lived for a long time largely because they had poor or compromised records of birth and death dates.
- apwell23 1y agoi haven't read it but i know the tl;dr. none of that shit works.
- OutOfHere 1y agoIt is spreading FUD wrt quercetin. It states there is just applicable one mammalian study which it doesn't even cite. In reality there have been multiple studies in humans showing no harm from a reasonable dose.
- snvzz 1y agoNo such discussion is complete without mention of SENS[0] i.e. the rejuvenation approach. Not about delaying the inevitable, but about undoing the accumulated damage of aging. 0. https://en.wikipedia.org/wiki/SENS_Research_Foundation https://en.wikipedia.org/wiki/SENS_Research_Foundation
- digitcatphd 1y ago“ Josh Mitteldorf studies evolutionary theory of aging using computer simulations.” > This is exactly why one must read the author before going into their content. What does this even mean?