Autophagy vs avoiding Frailty

I have seen a few videos recently in which different views have been expressed on the issue of maintaining muscle mass vs the merits of calorie restriction.

The argument has been put forward that calorie restriction results in to some extent the loss of muscle mass and in the long term frailty is to be avoided hence there are limits to the merit of CR.

I am not aware of any research that solidly looks at this conflict, but I thought it was an interesting topic for discussion.


We should add bone loss (density and quality) to the conversation about the consequences of chronic calorie and protein restriction.


It may be this sort of thing that means that being slightly overweight when older means lower mortality.


My 17.5 year old border collie might give us some insight. Typical lifespan for her breed is 13 to 15 years. We have had her since the age of 9. She has always been kept to a trim weight and has been taking rapamycin for 4 years now. I think the combo of rapa and mild caloric restriction has allowed her to avoid two of the big three killers of old dogs (cancer and cardiomyopathy) She does have kidney disease, but it is not severe yet. She is becoming weak and has bad hips.

If rapamycin therapy similarly allows humans to postpone our big three killers, strength training should be a serious consideration in order to maintain bone density and muscle mass. I wish our dog had been using a barbell, but there is no dog equivalent. I do walk up a steep hill with her every day.


You bring up a good topic here. I don’t understand the nuances of this area either. Definitely something that we need to dig deeply into, to understand…

See this thread and data: Even with calorie restriction, rapamycin slows muscle aging

It seems that rapamycin and CR both benefit in preventing muscle wasting, but there is also negatives I’m aware of (lower mTORC1 and muscle growth would seem an obvious issue longer term if you are on CR on a longer term basis).


It comes down to the question of muscle (and bone) growth and/or renewal. These require the correct nutrients and without those they don’t work as well. They also require the correct stimulus. The final part of the jigsaw is that the genome functions properly. In improving mitochondrial efficiency Rapamycin assists with the function of the genome.

CR to the extent that it causes weight loss also causes some muscle loss which can be reduced through exercise (particularly resistance training). Where this goes when frailty becomes an issue is perhaps the core of this balancing action. CR results, however, in more efficient mitochondria (for a similar reason to Rapamycin).


You are correct, IMO: CR to the extent that it causes weight loss also causes some muscle loss.

IMO: A very good pragmatic approach to longevity diets. A practical approach, whether you are vegan or an omnivore. Though I don’t believe in everything he says, he walks the walk and is in great shape for his age.

His main theme is keeping muscle mass into old age and he does discuss the balance of diet and autophagy.

He is a proponent of DoNotAge products, but in some of his most recent videos, he had lab tests comparing what he considered the top three supplement makers.

Optimal Longevity Diet: Discover the Surprising Results of 40 Years of Research


I have read papers to that effect recently.

I think it’s possible that both CR and protein restriction reduces frailty. Via mTOR and IGF-1.

However, in the short term, it might increase it. This is mitigated by simply being CR/protein restricted early life, and then not CR restricted/plenty of fat mass/ very late life. I haven’t heard of young people falling and breaking their hips.

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