Beginner's guide to longevity research(ldeming.com)
ldeming.com
Beginner's guide to longevity research
https://www.ldeming.com/longevityfaq
88 comments
While I agree with the general sentiment that CR is probably not very useful for humans, I think you are either misinformed or exaggerating for the sake of generating a response.
Ad-libitum feeding is not force feeding. Noone goes and shoves the food into mice. The food is just available.
Also, CR has extended lives in many species, including dogs (see https://avmajournals.avma.org/doi/abs/10.2460/javma.2002.220...), not just mice.
Ad-libitum feeding is not force feeding. Noone goes and shoves the food into mice. The food is just available.
Also, CR has extended lives in many species, including dogs (see https://avmajournals.avma.org/doi/abs/10.2460/javma.2002.220...), not just mice.
Ok, I'll concede that calling it force feeding is a bit tabloid, but the end result I described is undisputed - ad libitum feeding results in obesity in the control animals. Which indisputably muddies the waters for the results, since you don't know whether CR extends lifespans or AL feeding shortens lifespans in these animals.
The dog study you link also highlights another issue with this kind of research: they focus on osteoarthritis, i.e. cartilege in joints being worn out over time, since that was the most common chronic disease. This occurred equally often in both groups, but time until first treatment for this condition was 25% longer in the CR group. That's exactly what you expect just from the 25% reduced body mass of CR fed dogs which they report, since reduced body mass puts less stress on the joints. No attempt is made to account for this, it is not even mentioned as a confounding variable.
Taken together with the fact that they don't observe any significant increase in maximum lifespan of the CR fed dogs, it's again very unclear whether this is anything more than confirming the well-established result that when you inevitably get a chronic disease, higher body mass means you get sick faster.
The dog study you link also highlights another issue with this kind of research: they focus on osteoarthritis, i.e. cartilege in joints being worn out over time, since that was the most common chronic disease. This occurred equally often in both groups, but time until first treatment for this condition was 25% longer in the CR group. That's exactly what you expect just from the 25% reduced body mass of CR fed dogs which they report, since reduced body mass puts less stress on the joints. No attempt is made to account for this, it is not even mentioned as a confounding variable.
Taken together with the fact that they don't observe any significant increase in maximum lifespan of the CR fed dogs, it's again very unclear whether this is anything more than confirming the well-established result that when you inevitably get a chronic disease, higher body mass means you get sick faster.
Eh I’ve seen how dogs eat. They will eat until they puke. Mice may be doing the same.
Not sure why you are downvoted, most dogs are always really hungry and different even from an obese human.
Also while comparison to animals can be useful as a starting point it is no proof that it works anything like that in humans.
Also while comparison to animals can be useful as a starting point it is no proof that it works anything like that in humans.
I still haven't really figured out how CR is supposed to be sustainable. I am around BMI of 19, and have been as low as 17 (6'2", 133lb). I become extremely unhealthy when I don't eat enough. As far as I know, I can't eat less and maintain the same weight. CR would, for me, send me to the hospital. Is CR just another name for "lose weight"? Is it working towards a goal rather than a lifelong steady state of living?
Caloric restriction is an experimental tool that utilizes “undernutrition without malnutrition.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115619/
A simple interpretation of CR would be: “additional leanness from a normal body weight may add health and life span delaying the process of aging.”
Regarding BMI, rule of thumb is 20-ish.
CR in the NIA study reduces body weight by 25%, so the NIA CR “man equivalent” will have a BMI of 20.8 (in the lower half of the normal weight category)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115619/
A simple interpretation of CR would be: “additional leanness from a normal body weight may add health and life span delaying the process of aging.”
Regarding BMI, rule of thumb is 20-ish.
CR in the NIA study reduces body weight by 25%, so the NIA CR “man equivalent” will have a BMI of 20.8 (in the lower half of the normal weight category)
Ok, so really it's just about targeting a leaner body composition, that makes a lot more sense. Thank you.
I have the same body type. I've read about people doing CR who go from average body type to something like your or my body type (I was once 6' 135lb but I've gotten up to 150lbs lately).
As the OP say, there's very little basis to CR given you're talking mostly animals that are overeating and under exercising by default.
And mice are genetically uniform. CR has been partly tested on monkeys and other animals but it's a lot harder and results less conclusive.
As the OP say, there's very little basis to CR given you're talking mostly animals that are overeating and under exercising by default.
And mice are genetically uniform. CR has been partly tested on monkeys and other animals but it's a lot harder and results less conclusive.
> So it's entirely plausible all this caloric restriction research findings is just confirmation of the fact that obesity shortens lifespans.
Not entirely. It's accepted now that caloric restriction helps fighting cancer, so that effect alone means people following caloric restriction will live longer on average. Those feeding the cancers will simply die younger.
Not entirely. It's accepted now that caloric restriction helps fighting cancer, so that effect alone means people following caloric restriction will live longer on average. Those feeding the cancers will simply die younger.
Rejuvenation therapies and treatments that slow the progression of aging won't be tested in humans by waiting to see. They will be tested using quick before/after measures of biomarkers of aging. Those biomarkers are under development, and numerous types exist somewhere in the slow scientific process of standardization and debate. Here applied to calorie restriction, for example:
https://academic.oup.com/biomedgerontology/article/73/1/4/38...
"We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera–Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans."
That said, it is quite clear that research into provoking stress response isn't going to do much for longevity in humans, even while it may do useful things for long-term health in the same way as exercise and calorie restriction do. In addition to calorie restriction, growth hormone receptor knockout can be compared in mice and humans with Laron syndrome - the large gains in mouse life span don't occur in humans.
However, research into repairing the damage that causes aging is a whole different ball game. A completely different strategy, set of mechanisms, overall approach, and effect on the individual. A reversal of aging rather than a slight slowing of aging. We have no idea how results in mice will map to results in humans. So it is worth keeping an eye on the ongoing pilot trials and forthcoming larger trials of clearing senescent cells in human patients.
https://academic.oup.com/biomedgerontology/article/73/1/4/38...
"We obtained data from the National Institute on Aging CALERIE randomized trial through its public-access biobank (https://calerie.duke.edu/). The CALERIE trial randomized N = 220 nonobese adults to 25% caloric restriction (n = 145; 11.7% caloric restriction was achieved, on average) or to maintain current diet (n = 75) for 2 years. We analyzed biomarker data collected at baseline, 12-, and 24-month follow-up assessments. We applied published biomarker algorithms to these data to calculate two biological age measures, Klemera–Doubal Method Biological Age and homeostatic dysregulation. Intent-to-treat analysis using mixed-effects growth models of within-person change over time tested if caloric restriction slowed increase in measures of biological aging across follow-up. Analyses of both measures indicated caloric restriction slowed biological aging. Weight loss did not account for the observed effects. Results suggest future directions for testing of geroprotective therapies in humans."
That said, it is quite clear that research into provoking stress response isn't going to do much for longevity in humans, even while it may do useful things for long-term health in the same way as exercise and calorie restriction do. In addition to calorie restriction, growth hormone receptor knockout can be compared in mice and humans with Laron syndrome - the large gains in mouse life span don't occur in humans.
However, research into repairing the damage that causes aging is a whole different ball game. A completely different strategy, set of mechanisms, overall approach, and effect on the individual. A reversal of aging rather than a slight slowing of aging. We have no idea how results in mice will map to results in humans. So it is worth keeping an eye on the ongoing pilot trials and forthcoming larger trials of clearing senescent cells in human patients.
What you’re describing is not only the opposite of sound science and more likely to fool you than improve your life, but also a potentially hazardous money-grab. It is incredibly important not to fool yourself, to roughly paraphrase Feynman.
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Caloric restriction makes you live longer, but apparently so does exercise. The problem is though that exercise costs calories so you will be consuming more. How to square this contradiction?
This is a pretty fantastic writeup, short and simple on each topic with loads of sources.
For those looking for something actionable, you may want to head to the reddit board for intermittent fasting. It's a good way to lower your caloric intake and increase autophagy. People doing intermittent fasting often also eat a keto diet that is mentioned in the writing as well.
https://www.reddit.com/r/intermittentfasting/ https://www.reddit.com/r/keto/
For those looking for something actionable, you may want to head to the reddit board for intermittent fasting. It's a good way to lower your caloric intake and increase autophagy. People doing intermittent fasting often also eat a keto diet that is mentioned in the writing as well.
https://www.reddit.com/r/intermittentfasting/ https://www.reddit.com/r/keto/
I've lost about half my bodyweight, so I feel like my experience qualifies to me to offer my opinion that Keto's supposed anti-hunger effects are broscience crap.
Ephedrine or amphetamines, those work.
Ephedrine or amphetamines, those work.
I’ve never actually talked about this online before, but now I’m going to. I used to weigh over 560lbs, and I’ve lost 190 of that, with more going every week. I spent a lot of time on this, tried a lot of diets, tried medication, and ultimately considered surgery. In the end a ferocious commitment to eating less, eating better, and moving around more was what worked, and continues to work.
Years ago I went to a medically supervised weight loss program, twice, and met a loooot of people of all ages, all with serious weight problems. A few found success with surgery, and maybe half of those kept it off. Of the half that did, they knew going in that they were ready for the hard work, but they were so big they needed a boost to get moving.
The people who used drugs never kept it off. The the people who thought the magic was in some special way of eating never kept it off. The people who committed to lifelong lifestyle change kept it off, and it didn’t seem to matter if it was Keto, Atkins, Paleo, or any permutation of potentially healthy lifestyles. The active ingredient is not the plan, it is the desire to commit to the plan with all of your being... for years, forever.
For me at least, it was also a matter of growing the fuck up, really taking responsibility for my negative patterns of thought and behavior, and relentlessly working on them in a positive way. It’s hard, but I went from barely being able to walk, to jogging up stairs.
Everyone is a bit different, everyone has different issues with food and exercise, and everyone probably has to use a slightly different approach. Still, some constants for me were the need to ditch fast food completely, and soda is now a very rare treat. More than that however, I had to slowly alter my mental habits about food, and really pay attention to how I felt, especially after an unhealthy meal. I basically tried to form new habits to take the place of old destructive habits.
Anyway, enough babble from me, I just wanted to add my own perspective as someone doing the work to live, and live well.
Edit: I forgot to mention what actually made me post this in the first place, that I found intermittent fasting genuinely helpful. In particular I tend not to have cravings until after I’ve had my first real meal, so I just start a bit later, and have a defined cut-off. I have something with plenty of fiber in the morning, and then just lay off until lunch. More protein with each meal, less sugar, and plenty of fiber, and normal portions.
Years ago I went to a medically supervised weight loss program, twice, and met a loooot of people of all ages, all with serious weight problems. A few found success with surgery, and maybe half of those kept it off. Of the half that did, they knew going in that they were ready for the hard work, but they were so big they needed a boost to get moving.
The people who used drugs never kept it off. The the people who thought the magic was in some special way of eating never kept it off. The people who committed to lifelong lifestyle change kept it off, and it didn’t seem to matter if it was Keto, Atkins, Paleo, or any permutation of potentially healthy lifestyles. The active ingredient is not the plan, it is the desire to commit to the plan with all of your being... for years, forever.
For me at least, it was also a matter of growing the fuck up, really taking responsibility for my negative patterns of thought and behavior, and relentlessly working on them in a positive way. It’s hard, but I went from barely being able to walk, to jogging up stairs.
Everyone is a bit different, everyone has different issues with food and exercise, and everyone probably has to use a slightly different approach. Still, some constants for me were the need to ditch fast food completely, and soda is now a very rare treat. More than that however, I had to slowly alter my mental habits about food, and really pay attention to how I felt, especially after an unhealthy meal. I basically tried to form new habits to take the place of old destructive habits.
Anyway, enough babble from me, I just wanted to add my own perspective as someone doing the work to live, and live well.
Edit: I forgot to mention what actually made me post this in the first place, that I found intermittent fasting genuinely helpful. In particular I tend not to have cravings until after I’ve had my first real meal, so I just start a bit later, and have a defined cut-off. I have something with plenty of fiber in the morning, and then just lay off until lunch. More protein with each meal, less sugar, and plenty of fiber, and normal portions.
> The active ingredient is not the plan, it is the desire to commit to the plan with all of your being... for years, forever.
All of your post is good but this is the most important bit (IMO). The biggest scam the weight loss industry ever pulled on Western civilisation was the redefinition of "diet" from "what you eat" to "a temporary change in what you eat". To maintain a healthy weight you have to monitor your weight, and what you're eating, and adjust the latter in response to the former, forever. It's not a thing with an end. It's how you have to live.
All of your post is good but this is the most important bit (IMO). The biggest scam the weight loss industry ever pulled on Western civilisation was the redefinition of "diet" from "what you eat" to "a temporary change in what you eat". To maintain a healthy weight you have to monitor your weight, and what you're eating, and adjust the latter in response to the former, forever. It's not a thing with an end. It's how you have to live.
> To maintain a healthy weight you have to monitor your weight, and what you're eating, and adjust the latter in response to the former, forever.
Yeah, this is the part that people don't get when they talk about weight loss. They make it out like losing weight is the greatest thing, you'll feel better, have more energy, get more attention from the opposite sex, etc.
Truth is those benefits aren't guaranteed and are mostly exaggerated, but worse is the part they never talk about: what you're giving up to get there. Personally, I have to avoid (or leave early) social functions where free food will be available (you wouldn't believe how pushy people get, insisting that you eat), or that takes place at a restaurant (order a salad and everyone acts like you shot their dog). I have to suppress the urge to hit people who bring donuts to work. I spend three nights a week exercising and I eat a single meal a day of steamed vegetables and fake meat. I weigh myself every single morning and I make n effort to count every single calorie. And I have to do this for the rest of my life if I want to maintain where I am.
Weight loss is not a panacea, the tradeoffs aren't going to be worth it for everyone, and I really wish people would stop being such dicks about the whole thing.
Yeah, this is the part that people don't get when they talk about weight loss. They make it out like losing weight is the greatest thing, you'll feel better, have more energy, get more attention from the opposite sex, etc.
Truth is those benefits aren't guaranteed and are mostly exaggerated, but worse is the part they never talk about: what you're giving up to get there. Personally, I have to avoid (or leave early) social functions where free food will be available (you wouldn't believe how pushy people get, insisting that you eat), or that takes place at a restaurant (order a salad and everyone acts like you shot their dog). I have to suppress the urge to hit people who bring donuts to work. I spend three nights a week exercising and I eat a single meal a day of steamed vegetables and fake meat. I weigh myself every single morning and I make n effort to count every single calorie. And I have to do this for the rest of my life if I want to maintain where I am.
Weight loss is not a panacea, the tradeoffs aren't going to be worth it for everyone, and I really wish people would stop being such dicks about the whole thing.
Thanks very much, and I agree on all counts; it’s really the only advice I can give that I know to be true. You have to want to lose the weight and keep it off, to change profoundly, more than what you’ve been doing for years. The specifics are going to be different for various people, but the commitment over time is the big thing.
Good fuckin work, seriously.
> "I tend not to have cravings until after I’ve had my first real meal
Very much the case for me too, to the point that I can "forget" to eat all day so long as I really don't actually eat even a bit.
More importantly, though, I've found I can duplicate this effect to a great extent by strictly eliminating carbs from my first meal, and then a eating a proper square old-fashioned "dinner" in the afternoon. This has other benefits for me as well, the most noticeable being that I don't suffer grinding foggy sleepiness at midmorning or late afternoon. It also lets me be satisfied with a light supper later on, which is critical for my sleep. Big meals before bed leave me tossing and turning until early morning.
A sugary breakfast, on the other hand, will fuck up my whole day.
> "I tend not to have cravings until after I’ve had my first real meal
Very much the case for me too, to the point that I can "forget" to eat all day so long as I really don't actually eat even a bit.
More importantly, though, I've found I can duplicate this effect to a great extent by strictly eliminating carbs from my first meal, and then a eating a proper square old-fashioned "dinner" in the afternoon. This has other benefits for me as well, the most noticeable being that I don't suffer grinding foggy sleepiness at midmorning or late afternoon. It also lets me be satisfied with a light supper later on, which is critical for my sleep. Big meals before bed leave me tossing and turning until early morning.
A sugary breakfast, on the other hand, will fuck up my whole day.
I agree actually. You have to really want to change enough go through all the pain and suffering and to persist indefinitely. I have a lot of difficulty with hunger, to the point I couldn't fight it on will alone and would find myself compulsively eating and unable to stop myself. Rather than kill myself out of frustration over slowly undoing all that I had suffered for I kept trying different things until something worked, and that something was ephedrine.
Everyone responds differently to diet and exercise. For me, intense 30 min cardio makes me not hungry, which is probably counterintuitive for most people.
And for any nutrition plan,ensure you get all your macros in your feeding window too. I've totally found that hunger is suppressed by IF though, but only after a week or so of doing it. Even if you did everything right, maybe it's just not for your body.
And for any nutrition plan,ensure you get all your macros in your feeding window too. I've totally found that hunger is suppressed by IF though, but only after a week or so of doing it. Even if you did everything right, maybe it's just not for your body.
Exercise is an appetite suppressant (at least for the first hour or so afterwords).
There's more than one way to lose weight. A lot of people in the keto subreddit have lost a lot of weight too. Anecdotal evidence doesn't prove that keto is broscience. There's plenty of studies on it, even in the very article this thread is based on there is one sourced as linked to longevity.
Also here's a good youtube video explaining it: https://www.youtube.com/watch?v=Dan8qtgQRi8
Also here's a good youtube video explaining it: https://www.youtube.com/watch?v=Dan8qtgQRi8
Omega-3 fats are known to control hunger. That is probably where the claim that a high fat diet like keto can regulate appetite.
https://www.livestrong.com/article/296534-omega-3-as-an-appe...
https://www.livestrong.com/article/296534-omega-3-as-an-appe...
It's not about that. Here's a good youtube video explaining it.
https://www.youtube.com/watch?v=Dan8qtgQRi8
https://www.youtube.com/watch?v=Dan8qtgQRi8
I have made many attempts at fasting. I'm skinny as a rake and get very weak without some kind of constant caloric intake. I also get "hangry" and make bad decisions on an empty stomach.
Is this just me? Or is this a thing that everyone has and just works through?
Is this just me? Or is this a thing that everyone has and just works through?
1.) Start slow, you can start with something as short as 12hrs fasting (sleeping time counts) and just add an hour to that every week or two. Personally I added an hour as I get used to it. 14 hour fast and still not hungry yet? I'll add an hour to it this week. Now I generally just eat one meal per day unless I'm very active. 16hours fasting, 8 hours feeding window is the most common spot for people to stop.
2.) This is exactly why people who do intermittent fasting are often eating keto, which is a low carb, moderate protein, high fat diet. Carbs spike your blood sugar. Then it comes crashing down and puts you in a relative "low", so your body craves more of that quick energy and boom you are hungry/want carbs again.
Fats and proteins on the other hand give you a more stable energy level by not spiking your blood sugar as much. You stay full. The reason for only moderate protein is because excess protein is also turned into glucose through gluconeogenesis.
For the record my boyfriend is a black hole when it comes to food. He's fairly muscular and active so he gets hungry pretty quickly. But if he eats keto macros he can handle 1 meal a day too. He actually gets a bit sick eating carb heavy meals now.
I've seen people do it without doing keto and still get weight loss success, but a LCHF diet of some sort is the most common diet I see. Also the article mentions specifically keto diet linked to longevity.
Read through the sidebar info on the keto reddit if you want an idea of where to start.
2.) This is exactly why people who do intermittent fasting are often eating keto, which is a low carb, moderate protein, high fat diet. Carbs spike your blood sugar. Then it comes crashing down and puts you in a relative "low", so your body craves more of that quick energy and boom you are hungry/want carbs again.
Fats and proteins on the other hand give you a more stable energy level by not spiking your blood sugar as much. You stay full. The reason for only moderate protein is because excess protein is also turned into glucose through gluconeogenesis.
For the record my boyfriend is a black hole when it comes to food. He's fairly muscular and active so he gets hungry pretty quickly. But if he eats keto macros he can handle 1 meal a day too. He actually gets a bit sick eating carb heavy meals now.
I've seen people do it without doing keto and still get weight loss success, but a LCHF diet of some sort is the most common diet I see. Also the article mentions specifically keto diet linked to longevity.
Read through the sidebar info on the keto reddit if you want an idea of where to start.
Thanks for the encouraging response, I will definitely checkout the keto subreddit.
Yeah, came here to echo the idea that fasting is MUCH easier on a low carb diet. If you start reading about keto, you'll probably see the classic macro ratio of 75% fat, 20% protein, 5% carbohydrate – sometimes even higher percentage from fat.
My advice is that starting out, I wouldn't get too hung up on the ratio. It's actually pretty hard to get 75% of calories from fat. IMO, the important part is to limit the carbs. If you're hitting something like 60% fat, 30% protein, 10% good carbs (mostly green veggies, maybe some berries), you'll still see most of the keto benefits in terms of fewer mood swings and cravings, ability to fast more easily, etc.
Healthy eating is one of those areas where a lot of people (myself included) let perfect become the enemy of good. Even moderate low-carb, just eating cutting out sweets and starches, can be enough for a lot of people to see waistline and mood stability improvements.
My advice is that starting out, I wouldn't get too hung up on the ratio. It's actually pretty hard to get 75% of calories from fat. IMO, the important part is to limit the carbs. If you're hitting something like 60% fat, 30% protein, 10% good carbs (mostly green veggies, maybe some berries), you'll still see most of the keto benefits in terms of fewer mood swings and cravings, ability to fast more easily, etc.
Healthy eating is one of those areas where a lot of people (myself included) let perfect become the enemy of good. Even moderate low-carb, just eating cutting out sweets and starches, can be enough for a lot of people to see waistline and mood stability improvements.
I'm like you pretty skinny. I started IF and also going to the gym to try and put on weight. I never liked eating breakfast but did it because I thought it was something I had to do.
It took me maybe a week or two of not eating breakfast until it felt normal - but now I could never go back. I feel much more in control. Before if I missed breakfast i'd be a mess and my stomach would be making all kinds of noises in meetings. Another plus I can eat massive lunches and dinners to make up for what I didn't eat at breakfast. I've still been able to gain weight this way!
It took me maybe a week or two of not eating breakfast until it felt normal - but now I could never go back. I feel much more in control. Before if I missed breakfast i'd be a mess and my stomach would be making all kinds of noises in meetings. Another plus I can eat massive lunches and dinners to make up for what I didn't eat at breakfast. I've still been able to gain weight this way!
I might try this, not because I believe in IF, but just because breakfast is annoying.
Does coffee count as breakfast here, though?
Does coffee count as breakfast here, though?
Black is fine. But protein (creamer) or sweetener(sugar/artificial) both spike your insulin which lessens autophagy. As the OP Article points out, autophagy leads to longevity in mice and lessens your chance of neurological disease.
In 2016 a Nobel prize was given to Yoshinori Ohsumi for his work on autophagy. "After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging. Disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases." [1]
That said, Dr. Jason Fung says black is better but he allows creamer if needed so that people stick with their fasts.
[1]https://www.nobelprize.org/nobel_prizes/medicine/laureates/2...
In 2016 a Nobel prize was given to Yoshinori Ohsumi for his work on autophagy. "After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging. Disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases." [1]
That said, Dr. Jason Fung says black is better but he allows creamer if needed so that people stick with their fasts.
[1]https://www.nobelprize.org/nobel_prizes/medicine/laureates/2...
Ya, black coffee is fine. I can't remember the number but if it's under like 50kcal I think you'll stay in the fasting state, so you can even have like a small fruit. Definitely double check this though :p
Not if it's black.
This could just be broscience (I have no formal education in these matters) but I've heard that the need to constantly have calories can be mitigated by eating a ketogenic diet, as it prepares your body to be able to run off of your fat reserves efficiently. If you are in ketosis due to diet all the time then it is easier to fast because your body is already in ketosis. Obviously if you are skinny as a rake you will want to make sure to make up for fasting periods by eating a lot of food during your feeding window, as I doubt you are trying to lose weight.
I will state from first hand, anecdotal experience that a ketogenic diet greatly reduced hangry feelings for me. I ate to satiation at meals, and I could go much longer without eating.
Depends what you're eating.
Sugar / carbs => Insulin spike > insulin drop > hangry within 2-3 hours
Protein / fat => Smooth sailing for 4-5 hours or more, hunger is much less intense
Just my experience.
Sugar / carbs => Insulin spike > insulin drop > hangry within 2-3 hours
Protein / fat => Smooth sailing for 4-5 hours or more, hunger is much less intense
Just my experience.
What's your BMI & BF%? IMO as another skinny person, you should probably clean up your diet and put on some healthy weight (muscle & bone) first.
The discussion about carbs, keto, etc applies to some people, but for the truly skinny, that feeling of weakness is your body slowly starving.
The discussion about carbs, keto, etc applies to some people, but for the truly skinny, that feeling of weakness is your body slowly starving.
Also, a good subreddit for IF and weight training: https://www.reddit.com/r/leangains/
My diet is almost small these days but I'm very curious about IF... Hoping I'll have willpower to do one
This is partially why I mentioned keto, keto keeps your blood sugar level very even so you don't get hungry as much. I find eating once per day to be quite easy as long as I eat the correct ratio of fat/protein/carbs. Also I worked up to eating once per day so that helped. (14 hrs for 2 weeks, then 15 hrs for 2 weeks, 16 hours for 2 weeks, etc.)
Honestly, it takes less willpower to do IF than to not do it :p
1. Wake up
2. Make Breakfast
3. Go on with day
vs
1. Wake up
2. Go on with day.
1. Wake up
2. Make Breakfast
3. Go on with day
vs
1. Wake up
2. Go on with day.
Less work doesn't necessarily mean less willpower. Maybe you don't get very hungry, but some people do and for them that's what makes it take more willpower to fast than not fast.
Another thing to consider is that many people who don't feel like spending the effort to make breakfast will just buy something and eat it. Doesn't take much effort or willpower to stop at Dunkin Donuts or Starbucks on the way to work.
Another thing to consider is that many people who don't feel like spending the effort to make breakfast will just buy something and eat it. Doesn't take much effort or willpower to stop at Dunkin Donuts or Starbucks on the way to work.
First there's the adaptation period. Even after you're adjusted you'll experience hunger sometimes, but once you start moving and have a coffee, tea or water, the hunger subsides. The only will power you'd need is just to have your morning drink before acknowledging you're hungry.
one shot are easy, it's the semblance of regularity that is important
Just try. For me that was way easier than expected.
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The author of this overview, Laura Deming, runs the Longevity Fund, and has a research background in the study of aging. She merits congratulations for being, I think, the first by a few years to put together a longevity-focused fund, now joined by e.g. Jim Mellon's Juvenescence venture, Methuselah Fund, Apollo Ventures, etc.
Rejuvenation research after the SENS Research Foundation model of repairing the known root causes of aging is a massive arbitrage opportunity. It remains the case that most people just don't get it, and are thus enormously undervaluing research and companies in this space. That is changing in senescent cell clearance, but six or seven other nascent areas of research and development are in exactly the same position senescent cell clearance was in back in 2010 - no attention, little funding, low valuation, huge potential for breakout gains in said valuation on producing a technology demonstration for rejuvenation in animal models.
It seems likely that the Longevity Fund will do well on the basis of having invested in Unity Biotechnology alone, even putting aside any other successes. The article linked here is a useful overview, with copious references, of the type of work presently taking place in the aging research community. It well illustrates that, aside from senescent cell clearance, nearly everything that counts as a major interest by funding and number of scientists involved is a form of tinkering with stress response biochemistry to modestly slow aging - not addressing root cause molecular damage by repairing it, but rather messing with metabolism to slow damage accumulation. Nowhere near as helpful.
Given what we know, where the data exists to compare outcomes between short-lived and long-lived species, the approach of altering metabolic processes to enhance beneficial stress response mechanisms is not going to move the needle all that far in humans. The results should be exercise-like and calorie-restriction-like in that they have worthwhile effects on long-term health, assuming that the cost of development and treatment is low, but they won't add much more to life expectancy than those two items are capable of achieving - which means perhaps the low end of five to ten years at best in our species, assuming life-long commitment to the intervention. Given that senescent cell clearance is a going concern, and other damage repair approaches such as cross-link breaking should follow in the years ahead, we can hope that the focus of the research community will shift as other approaches prove themselves much more cost-effective and successful.
Rejuvenation research after the SENS Research Foundation model of repairing the known root causes of aging is a massive arbitrage opportunity. It remains the case that most people just don't get it, and are thus enormously undervaluing research and companies in this space. That is changing in senescent cell clearance, but six or seven other nascent areas of research and development are in exactly the same position senescent cell clearance was in back in 2010 - no attention, little funding, low valuation, huge potential for breakout gains in said valuation on producing a technology demonstration for rejuvenation in animal models.
It seems likely that the Longevity Fund will do well on the basis of having invested in Unity Biotechnology alone, even putting aside any other successes. The article linked here is a useful overview, with copious references, of the type of work presently taking place in the aging research community. It well illustrates that, aside from senescent cell clearance, nearly everything that counts as a major interest by funding and number of scientists involved is a form of tinkering with stress response biochemistry to modestly slow aging - not addressing root cause molecular damage by repairing it, but rather messing with metabolism to slow damage accumulation. Nowhere near as helpful.
Given what we know, where the data exists to compare outcomes between short-lived and long-lived species, the approach of altering metabolic processes to enhance beneficial stress response mechanisms is not going to move the needle all that far in humans. The results should be exercise-like and calorie-restriction-like in that they have worthwhile effects on long-term health, assuming that the cost of development and treatment is low, but they won't add much more to life expectancy than those two items are capable of achieving - which means perhaps the low end of five to ten years at best in our species, assuming life-long commitment to the intervention. Given that senescent cell clearance is a going concern, and other damage repair approaches such as cross-link breaking should follow in the years ahead, we can hope that the focus of the research community will shift as other approaches prove themselves much more cost-effective and successful.
Very interesting research, but trying to derive actionable recommendations for humans seems a bit laughable at this point. Still seems tough to become immortal these days. Harvesting young blood, a rigid diet, castration and starving yourself occasionally - lots of effort your self-absorbed wealthy investor with a desire to live forever has to go through.
But then again, Sam Altman recently praised China for having fewer ethical concerns in that regard, so maybe they will get some longitudinal human studies going. The population scale full-genome analyses that are currently underway might also be helpful.
But then again, Sam Altman recently praised China for having fewer ethical concerns in that regard, so maybe they will get some longitudinal human studies going. The population scale full-genome analyses that are currently underway might also be helpful.
Actionable things for humans at the moment appear to look like trying senolytic drug candidates in rational self-experimentation, with before/after tests of metrics linked to tissue stiffness, inflammation, kidney and heart function.
Clearing senescent cells very clearly produces a degree of rejuvenation in mice, and can turn back progression of aging and specific age-related diseases via a sizable number of metrics.
Of those senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI if you are fine with using peptides lacking human data. Both of which should be filed under the "risk that needs to be well understood" category. Or you could wait a few years for the first human trials to run through and more data and better drug candidates to arrive.
But these things are on the menu of possibilities, and are not expensive at all to carry out as exploratory tests.
Clearing senescent cells very clearly produces a degree of rejuvenation in mice, and can turn back progression of aging and specific age-related diseases via a sizable number of metrics.
Of those senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI if you are fine with using peptides lacking human data. Both of which should be filed under the "risk that needs to be well understood" category. Or you could wait a few years for the first human trials to run through and more data and better drug candidates to arrive.
But these things are on the menu of possibilities, and are not expensive at all to carry out as exploratory tests.
The problem with all potential senolytic drugs is cancer. Looking at all the animal models (and spontaneous human mutations) where senescence is reduced there is a corresponding increase in cancer. We really can't do much about ageing until we can cure or prevent cancer.
That would only be the case in the models where senescence is blocked completely.
If instead for a short time killing some fraction of all currently existing senescent cells, the effect on cancer risk should be a reduction, due to decreased inflammatory signaling from those cells. The senescent cells that are hanging around at any given moment in time aren't helping you in any way; they're not reducing the risk of cancer. If there are enough of them, they are in fact increasing the risk of cancer due to messing with the surrounding environment. If those senescent cells ever actually helped, then that help was applied at the time the cell became senescent - and shortly thereafter it became a liability that should be destroyed.
There are emerging exceptions to that view, such as adaptive senescence in the immune system and possibly in support cells in the brain, but fortunately both of those should be largely moot points for the early senolytic therapies, and don't seem to be obstacles in old mice.
If instead for a short time killing some fraction of all currently existing senescent cells, the effect on cancer risk should be a reduction, due to decreased inflammatory signaling from those cells. The senescent cells that are hanging around at any given moment in time aren't helping you in any way; they're not reducing the risk of cancer. If there are enough of them, they are in fact increasing the risk of cancer due to messing with the surrounding environment. If those senescent cells ever actually helped, then that help was applied at the time the cell became senescent - and shortly thereafter it became a liability that should be destroyed.
There are emerging exceptions to that view, such as adaptive senescence in the immune system and possibly in support cells in the brain, but fortunately both of those should be largely moot points for the early senolytic therapies, and don't seem to be obstacles in old mice.
> trying senolytic drug candidates in rational self-experimentation
> senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI
How does one go about self-experimentation? FOXO4-DRI is for sale on the internet, but one needs a doctor to read the mouse studies and formulate a treatment plan. The same goes for dasatinib plus quercetin. In the mouse models it needs to be administered monthly. Is there a country one can visit today that has access to these peptides and drugs and willing doctors to create a plan?
> senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI
How does one go about self-experimentation? FOXO4-DRI is for sale on the internet, but one needs a doctor to read the mouse studies and formulate a treatment plan. The same goes for dasatinib plus quercetin. In the mouse models it needs to be administered monthly. Is there a country one can visit today that has access to these peptides and drugs and willing doctors to create a plan?
I'll get to publishing a detailed essay on that topic at some point in the near future. The less detailed precursor overview can be found here:
https://www.fightaging.org/archives/2017/05/planning-a-singl...
You don't need a doctor to figure out a treatment plan, you just need to put in some time to get familiar with reading research papers, the terminology, how researchers describe things, and the methodology used to move from animal to human exploratory studies. And an understanding of the risk - as doctors are usually pretty bad at explaining that in any case. It really isn't rocket science, and it is all copiously documented in scientific and other literature.
Also D+Q isn't administered monthly, it is a one-off treatment that, assuming it works in humans in the same way it does in mice, certainly wouldn't need to be done more than once every few years. It removes the cells it can remove, and then isn't going to do any more until new senescent cells arise at their slow pace. The people out there taking it frequently as though it were a supplement are just not acting sensibly, and don't understand the research.
https://www.fightaging.org/archives/2017/05/planning-a-singl...
You don't need a doctor to figure out a treatment plan, you just need to put in some time to get familiar with reading research papers, the terminology, how researchers describe things, and the methodology used to move from animal to human exploratory studies. And an understanding of the risk - as doctors are usually pretty bad at explaining that in any case. It really isn't rocket science, and it is all copiously documented in scientific and other literature.
Also D+Q isn't administered monthly, it is a one-off treatment that, assuming it works in humans in the same way it does in mice, certainly wouldn't need to be done more than once every few years. It removes the cells it can remove, and then isn't going to do any more until new senescent cells arise at their slow pace. The people out there taking it frequently as though it were a supplement are just not acting sensibly, and don't understand the research.
The reproduction angle is interesting, to me, anyway. The article only really talks about worms and then draws a vague link to Eunuchs - given social factors etc. neither is that meaningful.
What's more interesting is how my health/lifespan is impacted as a transwoman... Fertility is pretty badly hit by hormone therapy for both trans men and women, and in a few decades you should start having enough people to see how that actually affects outcomes. Of course... the social realities of being trans could confound that data. (E.g., being socially isolated is not good for your health)
What's more interesting is how my health/lifespan is impacted as a transwoman... Fertility is pretty badly hit by hormone therapy for both trans men and women, and in a few decades you should start having enough people to see how that actually affects outcomes. Of course... the social realities of being trans could confound that data. (E.g., being socially isolated is not good for your health)
Fertility being affected in trans men and trans women isn't a surprise. I'm curious though -- do you, as a trans woman, still intend to "father" a child? Do trans men still intend to become pregnant when it is the most female thing a person could do?
Why might a loss of fertility particularly matter to a trans person?
Why might a loss of fertility particularly matter to a trans person?
> Do trans men still intend to become pregnant when it is the most female thing a person could do?
The things that the broad society considers most central to gender stereotypes are not necessarily most central to (or even compatible with) individual gender identity. That’s true for cisgender individuals, and its also (perhaps even moreso) true for transgender individuals.
The things that the broad society considers most central to gender stereotypes are not necessarily most central to (or even compatible with) individual gender identity. That’s true for cisgender individuals, and its also (perhaps even moreso) true for transgender individuals.
I was interested in the context of longevity - of it being a "happy side effect" of dropping fertility. Trans men and women take hormones that make them infertile, does that enhance longevity?
Trans people often do desire to have biological children. I wish I had ovaries and a uterus and all of that, but I can't with the current state of medicine, so biologically, I'm limited to playing the male role. Hormones do nuke fertility, but I froze sperm beforehand.
I don't think the desire to have biological children is any different in trans people than it is in cis ones. I find the idea of being a mother much more appealing but that's not the hand I got dealt.
Trans men do become pregnant (look up the man who got pregnant, it was a bit of a news sensation)
Everyone experiences gender in their own way - "the most female thing a person could do" is not a fair way to describe it. Although I desire it, as a trans woman, I don't think of it as the holy grail of femininity. Perhaps biologically it is; but as a social creature how I am received socially matters more.
I also can nurse, it turns out, and if I ever did have children with my cis partner, that duty would probably fall to me.
Plenty of trans people, like cis people, have no interest in having children; still others are not invested in them being biological. It's a personal thing that varies with each individual.
Trans people often do desire to have biological children. I wish I had ovaries and a uterus and all of that, but I can't with the current state of medicine, so biologically, I'm limited to playing the male role. Hormones do nuke fertility, but I froze sperm beforehand.
I don't think the desire to have biological children is any different in trans people than it is in cis ones. I find the idea of being a mother much more appealing but that's not the hand I got dealt.
Trans men do become pregnant (look up the man who got pregnant, it was a bit of a news sensation)
Everyone experiences gender in their own way - "the most female thing a person could do" is not a fair way to describe it. Although I desire it, as a trans woman, I don't think of it as the holy grail of femininity. Perhaps biologically it is; but as a social creature how I am received socially matters more.
I also can nurse, it turns out, and if I ever did have children with my cis partner, that duty would probably fall to me.
Plenty of trans people, like cis people, have no interest in having children; still others are not invested in them being biological. It's a personal thing that varies with each individual.
This is an awesome write-up.
Regarding the experiment on monkeys that showed calorie restriction led to a longer life, there is one key point that I think damages the conclussion. Both groups of monkeys were fed an extremely unhealthy diet that was very high in sugar. So the conclusion would be that eating fewer unhealthy calories leads to a longer life, not that calorie restriction in itself does.
Regarding the experiment on monkeys that showed calorie restriction led to a longer life, there is one key point that I think damages the conclussion. Both groups of monkeys were fed an extremely unhealthy diet that was very high in sugar. So the conclusion would be that eating fewer unhealthy calories leads to a longer life, not that calorie restriction in itself does.
"long" interview with aubrey de grey from last december:
https://medium.com/@arielf/wake-up-people-its-time-to-aim-hi...
https://medium.com/@arielf/wake-up-people-its-time-to-aim-hi...
Very interesting and informative! As someone who knows nothing about this field, this was a really great summary! (I can only assume it's accurate unless someone chimes in to claim otherwise).
You guys should look at the "steak and eggs" diet. This is the best diet I did. You loose a lot of weight, feel amazing, no brain fog, you do not get crazy hungry. It's amazing!
That's because of the ketogenic aspect of it. Though I would get bored if I only ate Steak & eggs.
It's so easy you don't need to check how many carbs your food has because you only eat steaks and eggs. You can change how you cook your eggs or get different cuts of meat. And you can eat anything in the sixth day. It's the easiest and most efficient diet I tried so far.
Yes this is a great introduction into the topic. I would also recommend checking out www.leafscience.org home of the LEAF foundation. They are the guys who did that great video with Kurzgesagt last year and their website is packed with great info about aging and research.
https://www.youtube.com/watch?v=MjdpR-TY6QU
https://www.youtube.com/watch?v=MjdpR-TY6QU
Really well written article! And a lot of things I've never heard of.
While keto is mentioned, I do think that another diet deserves a mention here: WFPB (whole food plant based).
In the book, How Not To Die, Dr Greger bring together the science that underpins this diet. Some one switching to this from a standard american diet can expect to add some healthy years to their lives, based on sci evidence.
While keto is mentioned, I do think that another diet deserves a mention here: WFPB (whole food plant based).
In the book, How Not To Die, Dr Greger bring together the science that underpins this diet. Some one switching to this from a standard american diet can expect to add some healthy years to their lives, based on sci evidence.
Good point. See for example: The Whole Foods Diet: The Lifesaving Plan for Health and Longevity" by John Mackey, Alona Pulde, Matthew Lederman" https://www.goodreads.com/book/show/34837239-the-whole-foods...
Based on research studies cited there, the typical US American stitching from a SAD diet to a whole foods plant-based diet would live about ten years longer, and additionally have a much healthier and happier twenty years or so at the end with much lower likelihood of chronic illness or dementia.
See also: https://bluezones.com/live-longer-better/
For example: https://bluezones.com/exploration/loma-linda-california/ "Today, a community of about 9,000 Adventists in the Loma Linda area are the core of America’s Blue Zone region. They live as much as a decade longer than the rest of us, and much of their longevity can be attributed to vegetarianism and regular exercise. ... Adventists tend to spend time with lots of other Adventists. They find well-being by sharing each other’s values and supporting each other’s habits."
But even as good diet is essential, it is aspects of community and infrastructure that help people keep eating healthy together. Likewise, community and infrastructure can help promote daily exercise. So, ultimately, for most people, longevity is not an individual thing. It is a community thing.
That point on community is also made in the sequel to "Fat, Sick and Nearly Dead": https://en.wikipedia.org/wiki/Fat,_Sick_and_Nearly_Dead and is even made by Dean Ornish in the trailer: http://www.fatsickandnearlydead2.com/
Based on research studies cited there, the typical US American stitching from a SAD diet to a whole foods plant-based diet would live about ten years longer, and additionally have a much healthier and happier twenty years or so at the end with much lower likelihood of chronic illness or dementia.
See also: https://bluezones.com/live-longer-better/
For example: https://bluezones.com/exploration/loma-linda-california/ "Today, a community of about 9,000 Adventists in the Loma Linda area are the core of America’s Blue Zone region. They live as much as a decade longer than the rest of us, and much of their longevity can be attributed to vegetarianism and regular exercise. ... Adventists tend to spend time with lots of other Adventists. They find well-being by sharing each other’s values and supporting each other’s habits."
But even as good diet is essential, it is aspects of community and infrastructure that help people keep eating healthy together. Likewise, community and infrastructure can help promote daily exercise. So, ultimately, for most people, longevity is not an individual thing. It is a community thing.
That point on community is also made in the sequel to "Fat, Sick and Nearly Dead": https://en.wikipedia.org/wiki/Fat,_Sick_and_Nearly_Dead and is even made by Dean Ornish in the trailer: http://www.fatsickandnearlydead2.com/
I recommend Peter Attia's highly engaging and informative talk [0] on the same topic, which I think does a better job at articulating the motivation behind possible approaches to attacking the issue of health- and life-span.
[0] https://www.youtube.com/watch?v=vDFxdkck354
[0] https://www.youtube.com/watch?v=vDFxdkck354
I second this. I think Attia is one of the clearest thinkers on health, longevity and nutrition currently. Moreover, he is a trained doctor AND an ex-McKinsey consultant, a combination that marries a strongly analytical and numerical lens to a field (medicine) that notoriously isn't.
Thanks everyone for reading! I'll be around if you have any questions.
I have 3 questions:
1. Did you see the Park et al report on DNA-PK inhibition from earlier this year? https://news.ycombinator.com/item?id=14301878
2. Is anyone working on sleep? https://twitter.com/clumma/status/764842049199898624
3. Have you considered funding low-dose ionizing radiation research? https://www.facebook.com/clumma/activity/10151804061151737
1. Did you see the Park et al report on DNA-PK inhibition from earlier this year? https://news.ycombinator.com/item?id=14301878
2. Is anyone working on sleep? https://twitter.com/clumma/status/764842049199898624
3. Have you considered funding low-dose ionizing radiation research? https://www.facebook.com/clumma/activity/10151804061151737
It would be interesting to see a lab focussed on reproducing these findings and then running all the various combinations to see how those incremental improvements stack. Seems like something we should get ahead of before people run into unknown consequences of trying their own combinations.
That table at the end has a column "Median Lifespan Increase (treated/control)". No, it isn't an increase, it is a ratio.
Eg, the first entry, scenescent cell removal %135, is a 35% increase, not a 135% increase.
Eg, the first entry, scenescent cell removal %135, is a 35% increase, not a 135% increase.
It would be good to add the base size for the observed effect in each study.
Dr. Greger's talk is excellent with respect to how diet can influence longevity.
https://www.youtube.com/watch?v=7rNY7xKyGCQ
https://www.youtube.com/watch?v=7rNY7xKyGCQ
You may enjoy Dr Rhonda Patrick's podcast as well.
https://www.youtube.com/user/FoundMyFitness/
https://www.youtube.com/user/FoundMyFitness/
I know they're for illustrative purposes but I really would have appreciated some scales on those graphs.
Almost all animal testing is done on animals that manufacture L-Ascorbic Acid in their liver. L-Ascorbic Acid is an incredibly powerful hormone and completely discounting it's presence is foolish at best and negligent at worst.
I'm a bit surprised at no mention of importance of sleep. Why is that?
Or is this because that falls outside of scope of what "longevity research" in this case means?
Or is this because that falls outside of scope of what "longevity research" in this case means?
Seems to me an obvious target. Soundness of sleep seems to decline monotonically from near birth all the way to death
https://twitter.com/clumma/status/764842049199898624
https://twitter.com/clumma/status/764842049199898624
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if you are interested in the biopharma industry in general, in addition to the sources she lists on her site, here is a primer i recently put together: http://newbio.tech/blog.html
Why starve yourself by calorie restriction for 30 years when some bozo will shoot you dead in the end .
What's the end game here? A future ruled by 400 year old Zuckerbergs and other multi-trillionaires?
Much of the progress in society is possible only because previous generations eventually die off. What happens when that's no longer the case?
Much of the progress in society is possible only because previous generations eventually die off. What happens when that's no longer the case?
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Hope to God that you're dead by then.
Let's take caloric restriction, for instance, which is all the rage. Trouble is, all of the evidence we have is in mice or lesser animals, and the comparison is animals on caloric restriction against animals being force fed to the point of obesity. Let me repeat that: in research that shows caloric restriction increasing lifespan in animal models, they are not comparing to animals on a normal diet. So it's entirely plausible all this caloric restriction research findings is just confirmation of the fact that obesity shortens lifespans.
This isn't even touching on the point that correspondence between animal models and humans is abysmally bad. It's the best we have, but there's a very good reason drugs need to go through three stages of human testing after it's been proven successful in animals. With caloric restriction, we don't even have consistent positive results in monkeys, only in rodents.
Has any of this longevity stuff ever been tested in humans? Obviously not, since it would take many decades.
Some pointers for further reading:
https://www.sciencedirect.com/science/article/pii/S089158491...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765579/