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.
chasil · 5h ago
Taurine and Vitamin E are readily available and seem prudent.
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.
impure-aqua · 3h ago
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.
gddgb · 4h ago
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.
No comments yet
lumost · 5h ago
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.
DennisP · 5h ago
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.
cma · 2h ago
de Grey is not using sobriety as a lifestyle factor to reverse anything I'm pretty sure.
jaggederest · 4h ago
Especially selegiline, MAOIs are dicey business.
bob1029 · 7h 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.
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.
chasil · 5h ago
I have personally reduced my a1c from 6.2 to 5.3, mostly by fasting for 36 hours per week.
I already cut refined sugar out of my diet several years ago.
bradleyjg · 3h ago
> reduced my a1c
And therefore ?
zoeysmithe · 5h ago
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.
hgomersall · 5h ago
Is exercise really a maybe?
fwip · 5h ago
Even stuff like "don't be overweight" is a maybe. This meta-analysis famously found that being overweight actually has a moderate protective effect: https://pmc.ncbi.nlm.nih.gov/articles/PMC4855514/
jordanb · 46m ago
I feel like at the very least being overweight is harder on joints.
Also overweight is not obese.
motoboi · 5h ago
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
mvkel · 5h ago
Associating weight loss with the healthiness of oneself is a mistake.
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.
clumsysmurf · 40m ago
You can't meet your daily protein requirements in one meal. Also many vitamins / minerals compete for absorption so you don't want to consume all of them at the same moment either.
Eldt · 6h ago
Do you get acid reflux?
gautamcgoel · 6h ago
Simple solution: take an antacid, like Tums.
rscho · 5h ago
Which happily, is totally devoid of side effects.
schappim · 5h ago
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...
emporas · 5h ago
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.
AntiqueFig · 5h 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 · 5h ago
As in UV light?
echelon · 5h ago
GLP-1s are the first hint of that.
schappim · 5h ago
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...
lokrian · 5h ago
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.
lumost · 5h ago
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.
schappim · 4h ago
I'm reading that the US spends about $893 billion[1] on national defence and about $5.3 trillion on health care in 2024, with spending on track for roughly $5.6 trillion in 2025 [2][3]. These figures don't match my intuition...
Are you comparing total health care spending to direct government spending on the military?
pama · 7h ago
Be 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.
Aurornis · 6h ago
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.
A_D_E_P_T · 6h ago
lol, 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 · 5h ago
In plain English: scale by body weight then divide by 12.
rscho · 7h ago
Lack of pharmacology background doesn't seem like the biggest issue when extrapolating from mouse to human.
ac29 · 6h ago
> Be careful when reading such blogs
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
rscho · 5h ago
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.
andoando · 7h ago
I just learned this the other day, but its called allometric scaling. Definitely far off linear.
alkyon · 6h ago
Ascorbic 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.
RachelF · 39m ago
This, and the fact that Ascorbic acid leads to hardening of the arteries also makes it suspect.
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.
pretzellogician · 3h ago
Read a little further... it's specifically called ascorbic acid and vitamin C.
He probably just wanted to save space within the table.
malfist · 5h ago
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
wlonkly · 4h ago
Agreed, I would have appreciated this more as a peer-reviewed meta-analysis than a blog post.
Aurornis · 6h ago
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.
the__alchemist · 5h ago
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!
Aurornis · 4h ago
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)
rscho · 5h ago
Metabolic acidosis. Not trivial at all.
nutribueno · 6h ago
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.
balamatom · 5h ago
Underappreciated comment.
cj · 8h ago
From 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.
cm2012 · 7h ago
Your 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 · 7h ago
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.
Aurornis · 6h 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.
standardUser · 6h ago
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".
nahikoa · 7h ago
The correlation is unambigous. The causation is a different story, e.g. illnesses often cause weight loss.
loeg · 7h ago
And 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 · 5h ago
Is 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.
malfist · 5h ago
These 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 · 4h ago
Exenatide 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 · 2h ago
The 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?
adamgordonbell · 8h ago
Also 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.
obloid · 6h ago
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.
rscho · 6h ago
Don't come and spoil our nice individualism with populational effects, you filthy rationalist !
OutOfHere · 3h ago
What was the dose and frequency? I bet it was rather high. Or do you really think that 1 mg once per week will suppress the immune system?
rscho · 7h ago
How 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.
BobaFloutist · 3h ago
Never 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.
malfist · 5h ago
Oh there's plenty of people selling "side effect free" life extension supplements. But there's another name for side effect free medication: effect free.
cactusplant7374 · 8h ago
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.
YZF · 8h ago
The 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 · 7h 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.
lokrian · 7h ago
People are still getting nerve damage from too much vitamin B6 in energy drinks and vitamin supplements, and that's a well known and widely taken vitamin. The idea that you can take experimental drugs your entire life at little risk is optimistic.
rscho · 7h ago
Surprisingly, many people seem to think that pushing a few random pills into a machine optimized over some million years of evolution will tune it so it works better. Go figure...
Etheryte · 7h ago
It works for the majority of modern medicine, so it's not all that black and white.
rscho · 7h ago
Yes, although even for modern medicine curative and preventative strategies are very distinct. Sure, they'll give you pills to compensate for a problem you already have. But there are few meds that protect you against stuff you'll maybe catch in the future. Vaccines and antibiotics are obvious examples, but I'm not aware of many others. The rest of preventative strategies overwhelmingly consists in correcting deficits or excesses (calories, vitamins, sleep, exercise etc.)
jordanb · 8h ago
These roads people go down always arrive at eating collidal silver...
MarcelOlsz · 8h ago
Get with the times, methylene blue is the new it girl.
malfist · 5h ago
As a party trick, it'll make people pee blue. But don't do this, it isn't safe. Especially without consent
untrust · 7h ago
And sleep
hn_throwaway_99 · 6h ago
I 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 · 5h ago
Diet and exercise are well know for the effect you're looking for. Its just not easy
Animats · 8h ago
Winner, "Ascorbic". Do they mean Vitamin C?
YZF · 8h ago
The 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 · 4h ago
My 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?
FollowingTheDao · 5h ago
This 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 · 3h ago
Actually, those people lived for a long time largely because they had poor or compromised records of birth and death dates.
catigula · 7h ago
A 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.
bluGill · 7h ago
Realistically 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.
deadbabe · 6h ago
How 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.
Legend2440 · 2h ago
If people started to live longer, they would (hopefully) be in better health longer, and retire at a later age.
lumost · 5h ago
If 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.
ivape · 8h ago
Would any of the OTC stuff even be effective? Melatonin, NAC, and Berberine.
Truth 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 · 6h ago
If you want to live long, be bipolar and take lithium.
Melatonin is just for jetlag/otherwise shifted sleeping schedule, are people using it as an anti aging drug?
chasil · 4h ago
Melatonin 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.
OutOfHere · 2h ago
It 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.
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.
apwell23 · 5h ago
i haven't read it but i know the tl;dr. none of that shit works.
starchild3001 · 6h ago
This 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.
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.
starchild3001 · 5h ago
> You seem to be speaking about your own link, not the linked article on Hacker News.
Correct. The hacker-news linked article talks about drugs that made mice live longer, my article talks about drugs that made humans live longer with some supporting evidence from mice studies.
> Be especially careful with TRT advice on the internet or from local clinics that push TRT treatments.
Correct. If you read my article, it repeatedly talks about working with a Dr on this. Ideally an endocrinologist (in USA), or potentially a urologist.
Healthy doses of TRT, where studies found benefits are with hypogonadal men whose low T is verified via two separate tests (<200 or <250 total T). The dosages used (~100 mg / week or less) are nowhere near gym bro doses (~200, 300, 400 mg/week etc).
An endo will ask you to make lifestyle changes first, and resort to supplemental testosterone as a last resort.
> it’s on the short list of medicines that can make you permanently dependent by causing testicular atrophy.
I believe you're factually wrong on this. I know a lot of people personally who stopped TRT successfully, some after being a decade on it.
> It’s not appropriate to mix into a list of supplements to take
This is a non-sensical idea, because supplements are much like drugs except they don't go through the FDA approval proceess. They're simply unregulated drugs with potentially significant sides. You shouldn't take a light view of them.
Actually, if I were to choose between a drug and a supplement for the same problem (such as living longer), I think people should prioritize drugs first as they go through rigorous clinical trials, their side effect profile is well known, there's post-approval drug monitoring.
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.
No comments yet
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
I already cut refined sugar out of my diet several years ago.
And therefore ?
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.
Also overweight is not obese.
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.
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.
And UVs, don't forget UVs.
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[1] https://www.congress.gov/crs_external_products/IN/PDF/IN1242...
[2] https://www.healthaffairs.org/doi/pdf/10.1377/hlthaff.2025.0...
[3] https://www.healthsystemtracker.org/chart-collection/how-muc...
> 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
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.
He probably just wanted to save space within the table.
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)
> 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.
We've had plenty of time. Only their approval for weight loss is new
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.
> 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.
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.
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.
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?
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.
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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7553080
(no don't, it's hell on earth)
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.
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.
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-summa...
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.
Correct. The hacker-news linked article talks about drugs that made mice live longer, my article talks about drugs that made humans live longer with some supporting evidence from mice studies.
> Be especially careful with TRT advice on the internet or from local clinics that push TRT treatments.
Correct. If you read my article, it repeatedly talks about working with a Dr on this. Ideally an endocrinologist (in USA), or potentially a urologist.
Healthy doses of TRT, where studies found benefits are with hypogonadal men whose low T is verified via two separate tests (<200 or <250 total T). The dosages used (~100 mg / week or less) are nowhere near gym bro doses (~200, 300, 400 mg/week etc).
An endo will ask you to make lifestyle changes first, and resort to supplemental testosterone as a last resort.
> it’s on the short list of medicines that can make you permanently dependent by causing testicular atrophy.
I believe you're factually wrong on this. I know a lot of people personally who stopped TRT successfully, some after being a decade on it.
> It’s not appropriate to mix into a list of supplements to take
This is a non-sensical idea, because supplements are much like drugs except they don't go through the FDA approval proceess. They're simply unregulated drugs with potentially significant sides. You shouldn't take a light view of them.
Actually, if I were to choose between a drug and a supplement for the same problem (such as living longer), I think people should prioritize drugs first as they go through rigorous clinical trials, their side effect profile is well known, there's post-approval drug monitoring.