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?
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.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7553080
(no don't, it's hell on earth)
> 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.
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.
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.
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
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.
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!
But if i have routine labs done and find out i’m prediabetic, i have 2 choices. I could continue eating cookies every day like my mom did and not exercise, or i could make lifestyle changes and take metformin proactively.
Similarly with high blood pressure, and more. That alone addresses like 80% of modern ailments. Things get more tricky when we consider complex conditions like migraines, etc, which you have much less agency over as a person.
* different people can have different philosophies on life
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.
Also overweight is not obese.
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.
I already cut refined sugar out of my diet several years ago.
And therefore ?
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
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.
Also…lifting light weights for like 10 minutes a day at home is a lifechanger in the early days
It’s a life changer because when you’re at a significant caloric deficit, your body sheds both fat and muscle. When you lose muscle, your metabolic rate drops, also lowering your rate of fat loss
If you lift even a little, your body will hang on to muscle more effectively, making it easier to lose and maintain weight over a longer period
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
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.
Not all cells divide (neurons and some muscle cells don't divide); some cells divide very slowly. And in some cases telomeres may be repaired but this increases the risk of cancer [0]
https://biologyinsights.com/what-is-telomere-repair-and-is-i...
In other words, 100% of humans relying only or mainly on telomere repair will be faced with Alzheimer’s, Parkinson’s, and/or ALS, as well as cardiovascular diseases, before they reach 100 years old.
I would appreciate any pointers to a scientific article that describes this.
[0]: https://pmc.ncbi.nlm.nih.gov/articles/PMC6336700/
[1]: https://www.sciencealert.com/new-study-reveals-more-about-ho...
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.
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.
TRT is longevity to me. Feeling younger for as long as possible.
An "alarming study". You just have a puritanical mindset and can't stand someone else doesn't share your shitty sex life.
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)
From the perspective of "Should I be worried about side effects from taking this drug / should I not take this because it might give me this effect", I think this falls under "be aware of symptoms and stop or weigh the costs if you get it, but you're probably fine".
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.
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).
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?
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.
Hormonal contraceptives typically do not contain estradiol, but ethinylestradiol and/or progestins.
I know this because I recently had to source exogenous Estradiol for my wife after making this same mistaken assumption and being surprised at bloodwork and lack of improvement
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”
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...
And UVs, don't forget UVs.
---
[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...
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.
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.
Not about delaying the inevitable, but about undoing the accumulated damage of aging.
> This is exactly why one must read the author before going into their content. What does this even mean?
cj•5mo ago
> 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•5mo ago
> 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•5mo ago
jordanb•5mo ago
MarcelOlsz•5mo ago
malfist•5mo ago
YZF•5mo ago
I think there are some proper human trials happening but the jury is still out.
cactusplant7374•5mo ago
That's exactly my point. No one really knows the risk that they are taking.
rscho•5mo ago
Etheryte•5mo ago
rscho•5mo ago
lokrian•5mo ago
cactusplant7374•5mo ago
rscho•5mo ago
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•5mo ago
BobaFloutist•5mo ago
obloid•5mo ago
I'd be very wary of taking an immunosuppressive drug as an otherwise healthy person for theoretical life extension properties.
rscho•5mo ago
OutOfHere•5mo ago
loeg•5mo ago
FollowingTheDao•5mo ago
malfist•5mo ago
We've had plenty of time. Only their approval for weight loss is new
FollowingTheDao•5mo ago
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•5mo ago
FollowingTheDao•5mo ago
You’re saying this like it’s true already. Let’s give it 10 years.
malfist•5mo ago
Because it is true already? You take an obese person who has a lower quality of life because of their obesity and give them a drug that helps them lose that weight and keep it if, they're literally gaining function and a higher quality of life from it. Today.
FollowingTheDao•5mo ago
malfist•5mo ago
GLP-1s aren't remotely similar. Their approval was 20 years ago and have been in used by diabetics since.
haar•5mo ago
cm2012•5mo ago
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•5mo ago
nahikoa•5mo ago
standardUser•5mo ago
Aurornis•5mo ago
This doesn’t mean being slightly overweight from age 20 through 60 is an advantage.
untrust•5mo ago