#22

So it’s just a temporary diet, not a lifestyle? Once you get to a certain weight, you are no longer impacting mtor?

#23

You are impacting mtor, because it’s a nutrient sensing pathway. When you fast, you don’t have circulating nutrients, or access to external calories. This happens if you just stop eating, like overnight, though in a situation of excess caloric intake, or the body releasing fat storage resources in an overfed state, you may not experience nutrient deficit sensing.

The situation is different under CR. There are no excess calories, nutrients, as these are immediately utilized for tissue preservation and bodily functions. There is no reserve to draw upon. So the body spends all the time apart from the time of eating and digesting in a state of not sensing nutrients, and so mtor is not activated.

#24

That’s the good and the bad, as I understand it. Slower aging through less unnecessary “growth” but also less resilience and ability to recover unless you get the right balance (the right body weight target).

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#25

What happens when we keep reducing calories? Decades before I heard of rapamycin, I read that “Calorie restriction is the only thing shown to extend lifespan.”

Well, CR enough to extend lifespan is impractical for most people because of social pressures, etc.

Because I am retired and have few family or social obligations, I can basically do anything I want to.

Partly because of design and partly the natural inhibition of appetite as we grow older I have been able to observe the results of calorie restriction on myself.

I have been slowly reducing my daily caloric intake over quite some time. This has been a natural progression.

According to the Mayo Clinic calculator I need approx. 2150 calories/day.

Of course when I say that I am now consuming ~1600 caloriescals/day that is a very rough estimate and probably varies between 1800 & 1200 cals/day.

What I have noticed is the body reaches stasis at any particular calorie restriction. I.E., if you reduce your calories by 400/day you will lose weight until you reach a stasis point then all other things being equal you will stay at this weight. You will not continue to lose weight.

Currently, I am averaging around 168 lbs with an approx 550 cals less than the calculator says I should be eating. I have been maintaining this for several months.

I have done this by using time restricted feeding and a low carb diet.

Subjectively I feel a little less energetic and motivated, but that might be because of other factors.

IMO: Using time-restricted feeding results in reduced appetite.

I don’t recommend a calorie-restricted lifestyle, and I realize this might be very hard for some people. But, it is something you might consider trying if you want to extend your lifespan.

CR takes some time to achieve.

A very rough chart illustrating what I mean.

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#26

desertshores, I’ve read about and studied CR for decades (since the 80’s when I first read Walford’s book), and have practiced CR myself for many years. So, may I say something very, very strongly here?

Please be super careful initiating CR past about 50 years or so. Multiple studies have shown that CR initiated in late life can be extremely deleterious. CR shortens life in multiple animals, if initiated in late life. In fact, if anyone past 50 were to ask me about CR, I would recommend against it for health reasons, not social reasons.

If past 50 or so (I’m 66), it is healthy to not be overweight, and have good fat/muscle ratio. Aim for that. When going into the late 60’s 70’s 80’s, you don’t need to get rid of every scrap of fat - the game changes. A modest fat reserve can be protective. Exercise becomes critical, as it affects muscle as well as bone health. Somebody who is 80, and BMI of 24-25, with 15%-20% body fat is doing just fine. No need to push it any further.

CR is different from rapamycin wrt. age of initiation. Lifelong CR, as lifelong rapa will give you the greatest gains. But initiating CR in old age is dangerous and counterproductive, while it appears starting rapa in old age is fine and possibly helpful.

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#27

I agree with you but that’s my point. You get to a certain weight where you can no longer afford to calorie restrict and thus CR stops. It can’t be a life long intervention. Call it what it is. You go on a diet, get lean and stay that way which is healthy but not CR.

#28

I remember the definition given by Michael Rae,

a staunch practitioner of CR, at the deceased forum. According to his authoritative opinion, the degree of CR is always relative to the weight in the first adulthood, rescaled to a healthy lean mass. That remains a fixed reference, does not shift down when losing weight. You can express CR in calories, and that’s the amount of calories you ate in that point at time without changing bodyweight, or you can express the degree of CR in bodymass, which is simpler.

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#29

I’m going to put “CR” in with Intermittent Fasting, as terms that as of little use, poorly chosen words, and not well defined.

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#30

Thanks for this. This is the first time I heard this, and now I can stop thinking that CR is crazy. I already understood that my body had a range of weight stable positions, each dependent upon calorie intake and physical activity. The only way I can wrap my head around how to target a weight/ calorie intake is to set my activity level and then lower my calories / protein intake (weekly average) until I lose weight 100% of visceral / ectopic fat and then stop losing weight / bone / muscle. Augmenting this with rapamycin to help force additional autophagy on top of what I get from my exercise seems sensible.

Here is an interesting blog post from Michael Rae for others interested in exploring other ways of thinking about “hallmarks of aging”…