> 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 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.
> 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.
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.
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.
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.
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.
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.
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...
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.
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.
I am very certain that framing ageing as a disease that can be treated with a drug is a false oversimplication that can not yield meaningfull results.
Personaly I love complexity and trying to parse all of the moving peices in a problem, but ageing involves an unknown total number of peieces, and what we do know is daunting, many of the biological processes operate within tollerances of parts per billion, and the large number of processes effect each other.
The worst part of "anti ageing" is that it completly ignores the reality of lifestyle inputs demonstrably having accelerated ageing effects.
cart, horse
23 comments
[ 0.28 ms ] story [ 33.3 ms ] thread> 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.
> 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 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
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...
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.
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.
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.
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...
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.
0. https://en.wikipedia.org/wiki/SENS_Research_Foundation
> This is exactly why one must read the author before going into their content. What does this even mean?