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Dose-dependent effects of calorie restriction


BrianMDelaney

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Al Pater wrote (on the list):

 

Dose-dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin-like growth factor-1.

Nogueira LM, Lavigne JA, Chandramouli GV, Lui H, Barrett JC, Hursting SD.

Cancer Med. 2012 Oct;1(2):275-88. doi: 10.1002/cam4.23. Epub 2012 Aug 6.

PMID:23342276

http://onlinelibrary.wiley.com/doi/10.1002/cam4.23/full

http://onlinelibrary.wiley.com/doi/10.1002/cam4.23/pdf

 

Thanks to Al for this great news item!

 

We've known for a while that CR isn't an all-or-nothing phenomenon: a bit of CR yields a bit of benefit, more yields more. But here, we see that the way in which CR isn't all-or-nothing is not that the same genes are turned on to increasing degrees (or more frequently during a 24-hour period), but rather that different, additional genes turn on with increasing CR. Fascinating, and very useful! Some CR benefits might not arise at all with milder CR.

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  • 4 weeks later...

The dose-response benefits are what keep me interested in CR. Similar with the recent monkey studies in that the mildly restricted control group showed at least some of the benefits of the more restricted experimental group. People tend to group things into dichotomies, and I attest to having an all-or-nothing approach to many things. I've tried it this way and failed with CR (for psychological and social reasons, not so much physical), so knowing a 5-10% approach over time will give benefits is enough to keep me interested while easing into something more restricted over time. Studies like the one you posted are great to sate my curiosity and boost motivation.

 

I think the most successful long term approaches are dynamic, and this dose-response principle is very beneficial to my own very mild, but at times more restricted, CR. It also seems to be the mindset of the most successful long-term CR adherents. That is, they ebb and flow into more or less CR as it suits their current needs, rather than approaching it with an on or off approach. This comes in handy with injuries or illnesses, social interactions, dating (as Arturo recently posted), sports or exercise events, traveling, and so on. I think of it as an equation in which I try to constantly adjust the variables to net the greatest life-long enjoyment.

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There's really no research on how to optimize human CR. We don't even know for sure that it will extend lifespan in humans yet. CR was only discovered in 1934, so it hasn't even been a hundred years yet. That's certainly not enough time to test longevity in humans, never mind try to optimize it. We do know that biomarkers of health can improve with only a little CR and that it's dose dependent. We don't really have studies, but the experiences I've read about in CRSociety members suggest that there's a danger in going into the 35 % + range of calorie restriction. I'd guess the sweet spot where life is good and health is also good is between 20% and 35%, but we'll never know because the research takes too long to find out. It may also depend on individual circumstances, will power and activity level.

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  • 2 weeks later...

James, your approach to CR is exactly like mine: I started out very intense, but found the downsides too onerous (mostly: being scrawny; everything else, even the hunger, was manageable). This is why I scoured the research for evidence that CR wasn't all-or-nothing, and found reason to believe non-severe CR would yield significant benefits.

 

I also agree that a dynamic, flexible long-term approach is best, for some of us at least. Some CR benefits accrue quickly, others, unfortunately, much more slowly (Spindler showed this in rodents), but being able, or feeling able -- it's really more about a psychological trick to make CR feel more doable as a life-long choice -- to shift from severe to moderate CR when needed seems essential to me.

 

But now, pushing 50, doubting the optimism of my Kurzweilian futurist friends, and with the knowledge that I have more of my mother's die-early genes that my father's live-a-century genes, I'm probably going to stick to very serious, somewhat less flexible CR until something as good or better comes along.

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...with the knowledge that I have more of my mother's die-early genes that my father's live-a-century genes, I'm probably going to stick to very serious, somewhat less flexible CR until something as good or better comes along.

 

I read elsewhere you're doing a lot of "gene studying" relating to diet/cr.

 

What tests and expense is needed to find out which genes one has in dominance or benefiting longevity relating to inheritance from one side of the family or other? Do you need to test your parents' genes too? Is a hair sample sufficient if a gene test is required from parents?

 

Do you know of some good thread topics covering these subjects in more detail about the specific gene testing we should be doing?

 

Thanks. :)

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What tests and expense is needed to find out which genes one has in dominance or benefiting longevity relating to inheritance from one side of the family or other? Do you need to test your parents' genes too? Is a hair sample sufficient if a gene test is required from parents?

 

Figuring out which came from which side of the family generally would require having your parents tested, but for me the main thing was figuring what my risk was -- I mentioned my parents only because without genetic testing, I had to do it the old-fashioned way: looking at my family history.

 

Do you know of some good thread topics covering these subjects in more detail about the specific gene testing we should be doing?

 

This is all so incredibly new! A discussion about what SNPs (variations in genes) should be tested, and how to interpret the results, is about to explode in the world of medicine and health care. It's just beginning. I might try to attend the GET 2013 conference, where these topics will be covered.

 

http://www.getconference.org/

 

If I attend, I will certainly make a full report! But right now the most interesting discussions I've found are at 23andme.com.

 

Brian

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