There'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.
Of the prescription options, estradiol is probably the most common and easily available, between hormonal birth control and HRT.
It is also likely the most easy to study, as we have 60-70 years of usage that is not correlated with prevalence of other diseases that might skew life expectancy (like metformin etc.), and quite high-quality medical records by virtue of it being vended on a prescription basis.
Despite this, there is not really any clear evidence that it increases life expectancy.
Don’t listen to this stuff, he sounds so confident but it’s like he’s stapled together info nuggets. This isn’t like a thing people know with certainty.
There'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”
If 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.
In 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.
> 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.
While 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.
Autophagy research is all over the place and its hard to understand this stuff or make blanket statements, instead we just have to be flexible with it. Autophagy is always working and the ramp up happens pretty quickly for a lot of people. I think aiming for the 48-72 hour peak isn't helpful. Most people cant or wont fast that long. A lot of people on 16-18 hour daily fasts see benefits that suggest autophagy working well.
Also biology isnt computers, its not exact and all our bodies are very different. For example, say your standing autophagy rate is 3. 16-18 hours fasting its 7 out of 10. But at 48 hours its 10. The difference between 7 and 10 might not even be very meaningful on a practical health level. The difference between never getting to 7 because of "it takes 48 hours" thinking and never trying is then huge. Just a couple hours a day at level 7 autophagy or whatever could be life changing. I do about 14-16 hours a day and am happy I made that decision for myself. I do see benefits that are real seeming to me.
From what I've seen there's no real downside to 14-18 hour daily fasting and in theory incredible benefits. Its also worth mentioning for a lot of people just sleeping with an empty belly means a higher quality of sleep, so there's secondary benefits as well. Your gut 'taking a break' during those hours may also be another benefit in terms of gut health as well, but I'm more skeptical of that claim.
Personally I'd add 'consume and make tons of fermented food' to that list and also eat lots of prebiotics. Gut health is key to so many aspects of a healthy life - I have to imagine it helps with longevity (and lower stress). Nobody likes having stomach pain!
People love their probiotic pills but I'm not convinced - the amount of beneficial microbes is measured at bottling or production and who knows how many survive by the time they get to you. Not to mention how many survive into your gut once consumed.
Homemade sauerkraut or natto though? Pretty much guaranteed to be teeming with the stuff. And your grandparents and their parents were probably eating it their whole lives. It's a whole forgotten art / science that is thankfully making a comeback.
Anecdotally (obviously sample size of 1 so big grain of salt here) every person in my personal life who I saw live to a super long age and also maintain good mental fitness followed what you are saying above plus made their own fermented food into their elderly years.
At the worst it does nothing for longevity and you end up with more unique tasty food for yourself and your friends :-D
Fasting without any exercise has a hidden downside: you’re not just burning fat, you’re also burning muscle. Less muscle → lower glucose disposal capacity → systemic insulin resistance. The problem is that insulin resistance doesn’t stop in muscle — the brain is highly insulin-sensitive, and once central insulin signaling gets disrupted you start seeing network-level dysfunction and cognitive impairment (there’s a reason Alzheimer’s is sometimes called “type 3 diabetes”).
So yeah, autophagy is real, but pairing fasting with at least some resistance work is critical if you don’t want the “anti-aging hack” to backfire by accelerating muscle loss and brain decline.
Latest research (as in only ~2m old) dispels that narrative a bit but not entirely. Looks like spermidine is the autophagy signal but they’re not sure fasting does t always increase spermidine
Also…lifting light weights for like 10 minutes a day at home is a lifechanger in the early days
You can't meet your daily protein / caloric requirements in one meal. Also many vitamins / minerals compete for absorption so you don't want to consume all of them at the same meal either.
You are overstating the benefits of fasting. While it can be an effective weight loss strategy for some people, for those of us at a healthy weight there is no reliable evidence that it will improve lifespan compared to eating the same nutrients spread out across multiple meals.
I'm a large man and fairly active so I have to consume ~3000 kcal/day to maintain weight. If I try to eat that much in one meal it will make me physically sick. My digestive system just can't handle that much in one bolus.
What'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...
In the absence of actually lengthening the telomeres, everything falls short in the anti-aging department.
Most lifestyle habits contribute to shorting the telomeres as little as possible, which guarantees good health no matter the age, but still aging, albeit slower.
Given the current technology trajectory, many people including me, think that we are very close to totally stopping aging, and even reversing it.
You’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...
You missed the most important one, strong social connections. Maybe smoking might beat it out, but otherwise make sure you have a strong social network if you want to live longer (and with better quality of life).
This 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.
It's easy to poke at the military budget as wasteful, but human history has shown that military expenditure is at a minimum, necessary. The same cannot be said of most preferred spending avenues for the cause of the day.
> 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.
Scaling 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.
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.
I followed a link to another blog post of theirs in which they go on a rant claiming there was a conspiracy to suppress chloroquine and ivermectin as COVID treatments. I dont think anyone should be taking health advice from this person
Amusingly, this was a very common if not the most common stance on this very website some time ago. Surely, don't look for assistance on the internet regarding memory issues.
I 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
> 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).
These 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.
What 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!
For diabetics, Metformin is usually a net win. Having controlled diabetes is better all around than uncontrolled.
For non-diabetics hoping Metformin will bring health benefits, the subtle side effects like reducing adaptive responses to exercise ( https://pmc.ncbi.nlm.nih.gov/articles/PMC6351883/ ) and other small negatives aren’t usually advertised by the anti-aging influencers who only talk about the lifespan studies (in mice)
Shitty shits. Literally. As for metabolic acidoses, rates are extremely low (<10 cases per 100,000 patient-years, per https://pubmed.ncbi.nlm.nih.gov/26773926/), so it's almost a non-concern.
I'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.
This 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.
Which 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".
> 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.
I 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.
Rapamycin 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.
Readit News
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.
For melatonin, tryptophan plus niacin would maximize the serotonin pathway (note this is dangerous when used with SSRIs).
How many of these are easily available? I had no idea that royal jelly is sold as a supplement.
It is also likely the most easy to study, as we have 60-70 years of usage that is not correlated with prevalence of other diseases that might skew life expectancy (like metformin etc.), and quite high-quality medical records by virtue of it being vended on a prescription basis.
Despite this, there is not really any clear evidence that it increases life expectancy.
Given that actual honey on the shelf is often mere sugar water, and people buy chakra-alignment crystals online, what about the idea surprises you?
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”
Dead Comment
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
Also biology isnt computers, its not exact and all our bodies are very different. For example, say your standing autophagy rate is 3. 16-18 hours fasting its 7 out of 10. But at 48 hours its 10. The difference between 7 and 10 might not even be very meaningful on a practical health level. The difference between never getting to 7 because of "it takes 48 hours" thinking and never trying is then huge. Just a couple hours a day at level 7 autophagy or whatever could be life changing. I do about 14-16 hours a day and am happy I made that decision for myself. I do see benefits that are real seeming to me.
From what I've seen there's no real downside to 14-18 hour daily fasting and in theory incredible benefits. Its also worth mentioning for a lot of people just sleeping with an empty belly means a higher quality of sleep, so there's secondary benefits as well. Your gut 'taking a break' during those hours may also be another benefit in terms of gut health as well, but I'm more skeptical of that claim.
People love their probiotic pills but I'm not convinced - the amount of beneficial microbes is measured at bottling or production and who knows how many survive by the time they get to you. Not to mention how many survive into your gut once consumed.
Homemade sauerkraut or natto though? Pretty much guaranteed to be teeming with the stuff. And your grandparents and their parents were probably eating it their whole lives. It's a whole forgotten art / science that is thankfully making a comeback.
Anecdotally (obviously sample size of 1 so big grain of salt here) every person in my personal life who I saw live to a super long age and also maintain good mental fitness followed what you are saying above plus made their own fermented food into their elderly years.
At the worst it does nothing for longevity and you end up with more unique tasty food for yourself and your friends :-D
I already cut refined sugar out of my diet several years ago.
False. That would mean cellular debris would pile up unconstrained for pretty much everybody, which is clearly absurd.
> It is also an extreme cell response that is associated with high levels of cellular stress
Also false. It is a very essential cellular process. Read up on it, please.
So yeah, autophagy is real, but pairing fasting with at least some resistance work is critical if you don’t want the “anti-aging hack” to backfire by accelerating muscle loss and brain decline.
See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462531/ for brain insulin effect
Also…lifting light weights for like 10 minutes a day at home is a lifechanger in the early days
One can subsist on Oreos at a "healthy" weight if they consume <2,000 calories worth of cookies per day. They will not be a healthy person.
I'm a large man and fairly active so I have to consume ~3000 kcal/day to maintain weight. If I try to eat that much in one meal it will make me physically sick. My digestive system just can't handle that much in one bolus.
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...
Most lifestyle habits contribute to shorting the telomeres as little as possible, which guarantees good health no matter the age, but still aging, albeit slower.
Given the current technology trajectory, many people including me, think that we are very close to totally stopping aging, and even reversing it.
https://en.wikipedia.org/wiki/Epitalon
And UVs, don't forget UVs.
> 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.
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.
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.
I followed a link to another blog post of theirs in which they go on a rant claiming there was a conspiracy to suppress chloroquine and ivermectin as COVID treatments. I dont think anyone should be taking health advice from this person
He probably just wanted to save space within the table.
It kind of gross to call ascorbic acid like that, as someone who studied chemistry I'm revolted.
Many of the studies he refers to are old. There was a widely held belief in the early 1980's promoted by Linus Pauling that Vit C cured cancer.
Source?
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).
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.
For non-diabetics hoping Metformin will bring health benefits, the subtle side effects like reducing adaptive responses to exercise ( https://pmc.ncbi.nlm.nih.gov/articles/PMC6351883/ ) and other small negatives aren’t usually advertised by the anti-aging influencers who only talk about the lifespan studies (in mice)
> This is exactly why one must read the author before going into their content. What does this even mean?
> 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.
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.
This doesn’t mean being slightly overweight from age 20 through 60 is an advantage.
> 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.
I'd be very wary of taking an immunosuppressive drug as an otherwise healthy person for theoretical life extension properties.
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.