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CR might increase number of cancers


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Maybe. But this is the guy who DISCOVERED and characterized the MTOR pathway which is the foundation of cellular growth and hence highly relevant to cancer. He isn't somebody who just shoots from the hip. Most of us here on the list are well aware of David Sabatini as he's authored tons of papers over the years and is a prominent researcher whose work is highly relevant to longevity - without him, rapamycin would not even be looked at from that point of view. 

What I'm saying is that he's hardly some kind of amateur out of left field. I do agree that what he says is highly, HIGHLY counter-intuitive, for example his claim that intermittent fasting (specifically every other day fasting) is the worst of both worlds and likely strongly generates cancer. So I agree with you, Gordo insofar as that this sounds bonkers, but on the other hand I can't agree that this guy necessarily doesn't know what he's talking about - and after all, he claims his research does show elevated number of cancers in such scenarios.

I thought this extremely provocative and a good topic for conversation around these quarters, given how many around here incorporate CR or features of fasting into their regimen.

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You're welcome, Todd. If you do a search for David Sabatini on youtube, you will find a number of his lectures on the mTOR pathway, but there are also a lot of videos of him speaking on the biological pathways of cancer, including Q&A sessions. He's located at the Whitehead Institute for Biomedical Research at MIT, and very focused on cancer, so I do pay attention to what he says - again, whether he's right or wrong in this specific instance, he's not someone who I think of as "not knowing what he's talking about" in this space. 

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Thanks Tom.   I did find the clip interesting, although way too  brief and superficial.

Sabatini makes the following points (among others):

  1. There is substantial evidence that extended CR will likely increase human health and lifespan (there is contradictory evidence, though, as well.)
  2.  Although extended CR retards the growth of tumors, it appears to increase the number of tumors through increased stem cell activation.
  3.  If CR is halted and followed by a diet high in mutagenic foods, the CR-increased number of tumors could then become the basis for increased cancer.  Stem cells + mutation --> transformed cells -->  cancerous tumor growth.
  4. There are two possible solutions to  this problem:   a) remain calorie-restricted indefinitely; b) don’t eat a highly mutagenic diet
  5. But since CR influences many different physiological systems and affects many different disease processes  apart from cancer, simply reducing mutagenic food intake alone would not be expected have the same broad anti-aging effects as extended CR.
  6. Alternate day fasting is bad because CR benefits require at least two  weeks to materialize,  so all you get with A/D fasting is a boom and bust cycle.

I did not hear Sabatini claim that CR per se might increase number of cancers.   Rather, he repeatedly stresses that it is the alternation of CR with an ad lib mutagenic diet which is problematic.

I also did not hear Sabatini claim directly that alternate day fasting "likely strongly generates cancer."        What he says is that the A/D fasting period would be way too short to  have the same positive effects as extended CR, so it’s just a “boom and bust cycle”.   But if A/D fasting is too short to produce the positive effects of CR, wouldn't it also be too short to produce the negative tumor-initiation effects?   In any case, his remarks on A/D fasting are too brief to be of much interest.

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Tom, yes I am familiar with Sabatini's work and respect his scientific contributions.

Gordo didn't elaborate on what he disagreed with but there were a few statements by Sabatini I thought questionable.  His description of CR seemed a bit extreme as if it were an all or nothing dietary approach - 30 to 40% caloric restriction and a focus on some of the worst things that occur at the extremes of restriction such as lethargy and food obsession.  He also suggested there might be 1000 people practicing CR.  I'd be surprised if there are that many doing his described extreme CR long term with health and longevity as the motivation.   But there are undoubtedly far more doing moderate CR or extreme CR for other reasons such as anorexia.

As for the science, he is talking about an increase in tumors found in lab mice.  Perhaps this is relevant to us, but I don't know enough to reach that conclusion.  I could imagine many factors impact the relevance:  free living humans voluntarily restricting diet seeking optimal nutrition vs food deprived caged mice of questionable genetics in an unnatural environment with artificial lighting,  processed foods and in semi-sterile housing isolated from typical mouse biota.  People find imprisonment punishing and stressful and chronic stress is considered a risk factor for cancer.  Perhaps a semi-starvation diet exacerbates whatever chronic stresses imprisonment causes for a mouse?

The number of people doing involuntary CR likely falls in the range of millions to billions depending on the threshhold of deprivation one uses.  Their limited control of environment, difficulty obtaining a balanced diet of clean high quality foods and water and the other stresses of poverty and disempowerment may make the mouse studies statistically relevant for humanity but still largely irrelevant for those of us more privileged to be doing voluntary CR for longevity.

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