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Fasting for CR Benefits?

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U of Wisconsin-Madison reports a new study Fasting is required to see the full benefit of calorie restriction in mice

Some highlights:

The researchers discovered that, combined with eating less, fasting reduces frailty in old age and extends the lifespan of mice. And fasting alone can improve blood sugar and liver metabolism.

Surprisingly, mice that ate fewer calories but never fasted died younger than mice that ate as much as they wanted, suggesting that calorie restriction alone may be harmful.

 previous studies had unintentionally combined calorie restrictions with long fasts by providing animals with food just once a day. It was difficult, then, to distinguish the effects of one from the other.

To untangle these factors, Lamming's group designed four different diets for mice to follow. One group ate as much as they wanted whenever they wanted. Another group ate a full amount, but in a short period of time—this gave them a long daily fast without reducing calories.

The other two groups were given about 30% fewer calories either once a day or dispersed over the entire day. 

It turned out that many of the benefits originally ascribed to calorie restriction alone—better blood sugar control, healthier use of fat for energy, protection from frailty in old age and longer lifespans—all required fasting as well. Mice who ate fewer calories without fasting didn't see these positive changes.

Fasting on its own, without reducing the amount of food eaten, was just as powerful as calorie restriction with fasting. Fasting alone was enough to improve insulin sensitivity and to reprogram metabolism to focus more on using fats as a source of energy. The livers of fasting mice also showed the hallmarks of healthier metabolism.

The researchers did not study the effect of fasting alone on lifespan or frailty as mice aged, but other studies have suggested that fasting can provide these benefits as well.

"We need to know whether this fasting is required for people to see benefits," Lamming says. "If fasting is the main driver of health, we should be studying drugs or diet interventions that mimic fasting rather than those that mimic fewer calories."

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Thanks Corybroo,

1 hour ago, corybroo said:

Surprisingly, mice that ate fewer calories but never fasted died younger than mice that ate as much as they wanted, suggesting that calorie restriction alone may be harmful

Very interesting! Here is another writeup on this UW research on the effects of CR with and without fasting:

https://www.sciencedaily.com/releases/2021/10/211018112513.htm

Does anyone have access to the full text who could send it to me (dean at pomerleaus dot com)? I'd love to read it but I can't seem to access it via Sci-hub.

--Dean

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I just wonder if they let the poor mice that had their CR diet "dispersed over the entire day" sleep normally.  We have seen many CR studies of rodents eating CR diets as one to several times a day that showed not even a suggestion of such an effect.

Just saying, and yes the result are interesting and getting details of the study is important.

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On 10/18/2021 at 11:19 AM, AlanPater said:

I just wonder if they let the poor mice that had their CR diet "dispersed over the entire day" sleep normally.  We have seen many CR studies of rodents eating CR diets as one to several times a day that showed not even a suggestion of such an effect.

Just saying, and yes the result are interesting and getting details of the study is important. 

Yup to all those (and many more) skepticisms  .. incl. it's just one study, and ONLY mice, which ain't large, long-lived mammals, etc. etc. etc.

But Al ... if you can dig up the full study .... much 'preciated, pilgrim 😉

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https://www.nature.com/articles/s42255-021-00466-9.epdf?sharing_token=lQiUCR0n7ITbJous887BGdRgN0jAjWel9jnR3ZoTv0PkzkpUX6P_RxMHv-ZUQgkBAogjEi6gzSQPd3iOeNCU5-RSbqicCCqDK0GaG_VPI3tBPWSTAYU22807AcZdErWp1Zh4CoAX57M4OQzcP4_pjnf33xNZs1HMJ2rsS0-vfZc%3D

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As noted in the final cartoon "summary" in the paper as well as corybroo's OP ...

Quote

Fasting on its own, without reducing the amount of food eaten, was just as powerful as calorie restriction with fasting.

... well, my spidey sense is off the scale with this "deduction" ... and if my guts iz wrong .... Um ... Al Pater ...." Scotty you're fired" 😉

c9d82cef6d2ae3d08b71ac87403733ea.jpg&f=1

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I've had a chance to read this paper [1] comparing various combinations of fasting and CR in several strains of mice. There were basically 4 different dietary patterns the authors explored:

  1. Ad lib feeding (AL) - 24-hour access to regular rodent chow.
  2. Spread-out CR (aka diluted ad lib) - 24-hour access to same kind of chow but it was diluted with undigestible fiber so that mice ate pretty much throughout the active period but naturally got full and ate 30% fewer calories per day than AL.
  3. Time-restricted ad lib - access to regular rodent chow during a limited 3-hour window. The mice ate very close to the same amount as the AL mice, but over a short period of time so they spent much of the day in a fasted state.
  4. Punctuated Calorie Restriction - Like a normal CR experiment, where mice were given 30% less food than the AL mice consumed all at one time, which the gobbled down within about an hour and so spent most of the day in a fasted state.

They basically found that regular, punctuated CR (group 4) lived significantly longer and had all the usual markers of successful CR, including improved glucose levels and insulin signalling, reduced fraility late in life, better coat, better long-term memory and a bunch of changes in molecular pathways and increased longevity (+20%). The spread-out CR (group 2) showed many fewer of the usual changes associated with CR despite eating the same (reduced) number of calories. Compared with the punctuated CR mice, the spread-out CR mice had worse insulin sensitivity, increased fraility, a worse coat, and their metabolic pathways looked much more like AL mice than did the punctuated CR mice. Importantly, the spread-out CR mice lived 9% shorter lives on average than AL-fed mice. 

The authors argue that this shows that CR without accompanying fasting (i.e. spread-out CR) doesn't work, or doesn't work nearly as well as punctuated CR when it comes to improving health or extending longevity. The authors checked to make sure the nutrient absorption was such that the spread-out CR mice really did metabolize 30% fewer calories than the AL mice. But the authors do acknowledge that the chow dilution strategy could potentially have impacted the absorption of individual micronutrients and/or impacted the gut microflora.

Then they compared time-restricted AL feeding (group 3) to punctuated CR. The time-restricted ad lib mice ate very nearly as much as the continuous ad lib mice (i.e. ~30% more than the punctuated CR mice), but like the punctuated CR mice, they fasted for most of the day after gorging during their 3-hour window. The time restricted AL mice retained much more lean mass but had a similar (i.e. reduced) amount of fat mass as the punctuated CR mice.  They also closed resembled the punctuatad CR mice in terms of metabolic changes (e.g. glucose and insulin, fat vs. carb respiration), circadian rhythms, and gene expression. Unfortunately, they only followed these groups of mice for 16 weeks, so they couldn't compare longevity of the time-restricted AL mice with the punctuated CR mice - a major shortcoming IMO.

The authors say that together these results strongly suggests that CR without prolonged fasting times isn't (nearly as) effective and that prolonged fasting without CR may be (nearly) as effective as prolonged fasting with CR - i.e. the CR part may not be necessary. The authors point to two more recent studies [2] and [3] that suggest something similar.

Study [2] was particularly interesting. They compared feeding mice continuously as much as they wanted (AL), 30% less fed at one meal (which the mice ate quickly over 1-5 hours), or the same amount as the AL mice ate in a day but fed at one meal (which the mice ate over a longer 12-15 hours, but which still left them quite a few hours per day in a fasted state). The longevity benefits of the third group was about half that of traditional CR group, despite eating and weighing as much as the AL group and not being fasted for nearly as long per day as the CR mice. The authors of [2] similarly suggest that (much of) the longevity benefits of CR in traditional rodent (and primate) experiments may be a result of not (just) the fewer calories, but of the increased time spent in the fasted state. 

At the very least, it seems to me the evidence from these and other (human) studies suggest that time-restricted eating is healthy practice whether you are doing CR or not.

--Dean

-------------

[1] Nature Metabolism (2021)

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

Heidi H. Pak, Spencer A. Haws, Cara L. Green, Mikaela Koller, Mitchell T. Lavarias, Nicole E. Richardson, Shany E. Yang, Sabrina N. Dumas, Michelle Sonsalla, Lindsey Bray, Michelle Johnson, Stephen Barnes, Victor Darley-Usmar, Jianhua Zhang, Chi-Liang Eric Yen, John M. Denu & Dudley W. Lamming 

Abstract
Calorie restriction (CR) promotes healthy ageing in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting. Here we show that a prolonged fast is necessary for key metabolic, molecular and geroprotective effects of a CR diet. Using a series of feeding regimens, we dissect the effects of calories and fasting, and proceed to demonstrate that fasting alone recapitulates many of the physiological and molecular effects of CR. Our results shed new light on how both when and how much we eat regulate metabolic health and longevity, and demonstrate that daily prolonged fasting, and not solely reduced caloric intake, is likely responsible for the metabolic and geroprotective benefits of a CR diet.

https://doi.org/10.1038/s42255-021-00466-9

Full Text link.

--------

[2]  Cell Metab. 2019 Jan 8;29(1):221-228.e3. doi: 10.1016/j.cmet.2018.08.011.

Daily Fasting Improves Health and Survival in Male Mice Independent of Diet 
Composition and Calories.

Mitchell SJ(1), Bernier M(1), Mattison JA(1), Aon MA(2), Kaiser TA(1), Anson 
RM(3), Ikeno Y(4), Anderson RM(5), Ingram DK(6), de Cabo R(7).

The importance of dietary composition and feeding patterns in aging remains 
largely unexplored, but was implicated recently in two prominent nonhuman 
primate studies. Here, we directly compare in mice the two diets used in the 
primate studies focusing on three paradigms: ad libitum (AL), 30% calorie 
restriction (CR), and single-meal feeding (MF), which accounts for differences 
in energy density and caloric intake consumed by the AL mice
. MF and CR regimes 
enhanced longevity regardless of diet composition, which alone had no 
significant impact within feeding regimens. Like CR animals, MF mice ate 
quickly, imposing periods of extended daily fasting on themselves that produced 
significant improvements in morbidity and mortality compared with AL. These 
health and survival benefits conferred by periods of extended daily fasting, 
independent of dietary composition, have major implications for human health and 
clinical applicability.

Published by Elsevier Inc.

DOI: 10.1016/j.cmet.2018.08.011
PMCID: PMC6326845
PMID: 30197301 [Indexed for MEDLINE]

 

----------------

[3] Cell Metab. 2020 Jul 7;32(1):100-116.e4. doi: 10.1016/j.cmet.2020.04.018. Epub 

2020 May 14.

Untangling Determinants of Enhanced Health and Lifespan through a Multi-omics 
Approach in Mice.

Aon MA(1), Bernier M(2), Mitchell SJ(3), Di Germanio C(2), Mattison JA(2), 
Ehrlich MR(2), Colman RJ(4), Anderson RM(5), de Cabo R(6).

The impact of chronic caloric restriction (CR) on health and survival is complex 
with poorly understood underlying molecular mechanisms. A recent study in mice 
addressing the diets used in nonhuman primate CR studies found that while diet 
composition did not impact longevity, fasting time and total calorie intake were 
determinant for increased survival. Here, integrated analysis of physiological 
and multi-omics data from ad libitum, meal-fed, or CR animals was used to gain 
insight into pathways associated with improved health and survival. We 
identified a potential involvement of the glycine-serine-threonine metabolic 
axis in longevity and related molecular mechanisms. Direct comparison of the 
different feeding strategies unveiled a pattern of shared pathways of improved 
health that included short-chain fatty acids and essential PUFA metabolism. 
These findings were recapitulated in the serum metabolome from nonhuman 
primates. We propose that the pathways identified might be targeted for their 
potential role in healthy aging.

Published by Elsevier Inc.

DOI: 10.1016/j.cmet.2020.04.018
PMCID: PMC8214079
PMID: 32413334

Conflict of interest statement: Declaration of Interests The authors declare no 
competing interests.

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Then they compared time-restricted AL feeding (group 3) to punctuated CR. The time-restricted ad lib mice ate very nearly as much as the continuous ad lib mice (i.e. ~30% more than the punctuated CR mice), but like the punctuated CR mice, they fasted for most of the day after gorging during their 3-hour window. The time restricted AL mice retained much more lean mass but had a similar (i.e. reduced) amount of fat mass as the punctuated CR mice.  They also closed resembled the punctuatad CR mice in terms of metabolic changes (e.g. glucose and insulin, fat vs. carb respiration), circadian rhythms, and gene expression. Unfortunately, they only followed these groups of mice for 16 weeks, so they couldn't compare longevity of the time-restricted AL mice with the punctuated CR mice - a major shortcoming IMO.

Haven't looked at that dense paper as carefully as Dean yet .... so what were the WEIGHTS of the mice in the myriad groups ... especially group 3 vs group 4 ... and throughout the (yes, suspiciously attenuated!!) 16-week range? And did the group 3's actually FINISH all the AL meal in front of them?

Normally, the gut of an animal can only hold so much food before the stretch sensors reach thresholds and send a signal to the ol' noggin tellin' it, "youz iz full, fatso."

In other words ... "Time-restricted ad lib" (fasting) may be like gettin' y'alls stomachs stapled .... or: the digestive system can't handle all that much food at once, and some of it goes thru the digestive system (un-absorbed) and out the shitter.

Bottom line: we need animal weights. Preferably nicely charted.

 

 

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Just now, KHashmi316 said:

Haven't looked at that dense paper as carefully as Dean yet .... so what were the WEIGHTS of the mice in the myriad groups ... especially group 3 vs group 4 ... and throughout the (yes, suspiciously attenuated!!) 16-week range? And did the group 3's actually FINISH all the AL meal in front of them?

Normally, the gut of an animal can only hold so much food before the stretch sensors reach thresholds and send a signal to the ol' noggin tellin' it, "youz iz full, fatso."

In other words ... "Time-restricted ad lib" (fasting) may be like gettin' y'alls stomachs stapled .... or: the digestive system can't handle all that much food at once, and some of it goes thru the digestive system (un-absorbed) and out the shitter.

Bottom line: we need animal weights. Preferably nicely charted.

 

 

Unfortunately the link Luke shared no longer seems to work for me to access the paper and it wouldn't let me download it when I did have access. As I recall from the supplemental figures, the mice fed ad lib within a 3 hour window ate very nearly as much food as the mice given 24h access to food. So yes they "finished the meal" as you asked. Below is the only figure I screen captured of that experiment. As you can see from the graphs in b (upper left bar graphs), the time restricted AL-fed mice (TR.al) gained as much lean mass of the 16 weeks of the experiment as the AL mice (i.e. much more than the CR mice) but gained only a little bit more fat mass than the CR mice (i.e. much less than the AL mice).

--Dean

Screenshot_20211020-121100_Chrome.jpg

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From Fig. 3b, the BODY WEIGHT of the three groups is of interest. TR.al and CR seem more similar to each other than AL.

If you've gotta lotta stuff goin' thru the small intestine, only a certain amount will be in contact with the villi.

Hmm ... wonder what the "dwell time" is for food clearing the gut, in mice?   Digestive enzymes and acids have certain half lives (as well as limits in how of the them a body is willing to produce per feeding, errr.. .meal).  Organic matter (food) also has a "shelf life" in the gut -- before it itself begins to endanger the gut.

That is ... you eat ...and ... the dig system has an EVOLUTIONARILY time (de)limit on how much goes thru, in a period of time, before it is excreted.

So -- for the mice anyway, a non-feast/famine animal  -- TR.al  may have been effectively CR'd if we can trust Fig. 3b  BODY WEIGHTs.

Not sure feast-famine programmed humans can pull off TR.al .

"Calories, calories, calories."

Edited by KHashmi316

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2 hours ago, KHashmi316 said:

That is ... you eat ...and ... the dig system has an EVOLUTIONARILY time (de)limit on how much goes thru, in a period of time, before it is excreted

No absorption wasn't a factor. As you know from your monkey chow, these diets are highly refined and quickly digested. And furthermore, as I mentioned above, the authors did bomb calorimetry on the mice feces to verify the time restricted mice weren't pooping out extra calories that weren't being absorbed (Edit: actually now that I can see the paper [1] again (thanks Kenton!), it isn't clear that the researchers did bomb calorimetry on the time restricted group, only the diluted feeding group. But the RER graph of the time restricted group (Figure 3e) clearly shows the time restricted group having a higher and longer period of elevated digestive activity relative to the CR mice after feeding, suggesting they were absorbing the extra food they were given). 

But more interesting regarding the body weight issue was study [2] that I discussed briefly above. In [2], mice who had the same amount of food an AL-fed animal ate in a day dumped into their hopper all at once (rather than being freely available anytime they wanted), learned to eat a day's worth of food in an average of 12-15 hours, rather than "grazing" the same amount of food over a full 24 hours. 12-15 hours is obviously plenty of time to fully digest it, but still leaves them with 9-12 hours per day of being in the fasted state (unlike the true AL-fed mice who had food continuously available and ate nearly continuously over the day).

As you can see from the graphs A, B and C of this figure from [2], the (modestly) time-restricted fed mice (labeled NIA-MF and WIS-MF for the two diet compositions, to mimic the NIA and Wisconsin primate CR study diets) ate as much and weighed as much as the corresponding AL-fed mice that had continuous access to food throughout the 24 day, they just ate an AL-amount of food faster i.e. over 12-15 hours (as illustrated in the graphs D and E):

Screenshot_20211021-161706_Chrome.jpg

 

But despite eating and weighing as much as the continuous-AL mice, the time-restricted AL-fed mice lived significantly longer, enjoying about 1/2 the average longevity benefits of the 30%-CR'ed mice, without the food deprivation or the weight loss, as shown in these survival graphs:

Screenshot_20211021-164428_Chrome.jpg

So here we have a clear case where it isn't just "Calories, Calories, Calories".

On a side note - it is interesting that the graphs in C above show that the survival curves for equivalent groups (AL, MF or CR) for each diet composition (i.e. NIA or Wisconsin) were virtually identical, suggesting at least for mice, the greater amount of fat (F) and simple sugar (S) in the Wisconsin diet doesn't negatively impact longevity (i.e. It didn't cause the AL-fed mice on the Wisconsin diet to die extra early, making CR appear effective on the Wisconsin diet but not the "healthier" NIA diet, as some have hypothesized happened in the Wisconsin primate CR study as compared to the NIA primate CR study).

The interesting question that unfortunately wasn't answered in [1] was if an even shorter window to eat an AL-amount of food (i.e. 3h rather than 12-15h as in [2]) would result in even greater longevity benefits for the time-restricted mice, making them comparable in longevity to the 30% CR mice. Suggestive was the fact that in [2], the (modestly) time-restricted fed mice didn't show as big improvements in metabolic measures (e.g. Glucose and insulin) as the CR mice, while in [1], the (heavily) time-restricted fed mice showed nearly equivalent improvements in the same metabolic factors. This, and the fact that they didn't get nearly as obese as the AL-fed mice despite eating (and absorbing) almost exactly as many calories, suggests that if they had measured the longevity of the (heaviliy) time-restricted fed mice they may have live nearly as long as the CR mice. But obviously we won't know for sure until someone does a lifespan experiment using the same protocol.

--Dean

--------------------------

[2]  Cell Metab. 2019 Jan 8;29(1):221-228.e3. doi: 10.1016/j.cmet.2018.08.011.

Daily Fasting Improves Health and Survival in Male Mice Independent of Diet 
Composition and Calories.

Mitchell SJ(1), Bernier M(1), Mattison JA(1), Aon MA(2), Kaiser TA(1), Anson 
RM(3), Ikeno Y(4), Anderson RM(5), Ingram DK(6), de Cabo R(7).

The importance of dietary composition and feeding patterns in aging remains 
largely unexplored, but was implicated recently in two prominent nonhuman 
primate studies. Here, we directly compare in mice the two diets used in the 
primate studies focusing on three paradigms: ad libitum (AL), 30% calorie 
restriction (CR), and single-meal feeding (MF), which accounts for differences 
in energy density and caloric intake consumed by the AL mice
. MF and CR regimes 
enhanced longevity regardless of diet composition, which alone had no 
significant impact within feeding regimens. Like CR animals, MF mice ate 
quickly, imposing periods of extended daily fasting on themselves that produced 
significant improvements in morbidity and mortality compared with AL. These 
health and survival benefits conferred by periods of extended daily fasting, 
independent of dietary composition, have major implications for human health and 
clinical applicability.

Published by Elsevier Inc.

DOI: 10.1016/j.cmet.2018.08.011
PMCID: PMC6326845
PMID: 30197301 [Indexed for MEDLINE]

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Has there ever been any work to try to relate mice fasting times to human? In other words could you measure various blood markers in mice as they fast over say 15 hours, and then how long in human does it take to reach similar markers? Is it also just 15 hours, or due to the quicker metabolism of mice, would it take significantly longer than 15 hours for humans?

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 This, and the fact that they didn't get nearly as obese as the AL-fed mice despite eating (and absorbing)  almost exactly as many calories, suggests that if they had measured the longevity of the (heaviliy) time-restricted fed mice they may have live nearly as long as the CR mice. But obviously we won't know for sure until someone does a lifespan experiment using the same protocol.

Somethin' ain't addin' up. And it may very well be due to researchers "manipulating" the data to fit their purported fasting claims. 

But back to the WEIGHTs ... 

What about activity of the TR.al animals? We've heard reports of overuse of exercise wheels (etc) of CR animals. Some of human CRONies have personally experienced the same effect, esp. on heavy CR.

In the wild, mice spend most of their waking hours movin' around, foragn' for grub, or building nests. But if the grub is always avail., and they are in a small cage, then less activity  ... or: the urge for activity is still there so all the time food wasn't avail. .. it's wheelin' time.

Although this would be huge PITA experiment ... what  researchers need to do is admin. a CR diet (graduated portions) ... several times over animals' normal waking hours. I.e. a pure UN-FASTED CR regimen.

 

Edited by KHashmi317

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12 minutes ago, KHashmi317 said:

What about activity of the TR.al animals? We've heard reports of overuse of exercise wheels (etc) of CR animals. Some of human CRONies have personally experienced the same effect, esp. on heavy CR.

Khurram,

It would really be nice if you would actually read the paper before asking questions. From pg 1333:

The CR and TR.al groups demonstrated decreased total energy expenditure relative to the  Al-fed mice that was independent of lean (fat-free) mass and body weight (supplementary Figure 5).

Unfortunately I don't have access to the supplementary material so I can't post the referenced figure.

--Dean 

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'What's wrong with this picture?"

From P12 of Nature Metab. article: Fig. 7 | Fasting plays a critical role in the response to a CR diet. Summary figure highlighting that prolonged fasting is necessary and sufficient for many of the effects of CR. 

Look at the cartoon and read captions carefully. 

nature_s42255-021-00466-9_p12.jpg

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BTW:

We -- the orig List CR gang -- have been thru the fasting issue BEFORE, decades ago, on the CR List ... methinks merecall Michael Rae having disputed much of fasting .... anyone have access to the legacy posts? 

I think someone with better knowledge on this issue should pursue it relentlessly ... as it has the potential to do much harm .... CR folks giving up on CR ... authors selling yet another Fasting 4 health book, etc. etc.

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Yeah Khashmi,

We all know Michael Rae concluded it’s ‘calories, calories, calories’.  
That was before this latest study.

It’s  entirely possible it’s the pro-CR trance that needs to be dialed back a bit here- not ‘authors selling another book’.

It’s always quite likely that life extension due to CR corresponds to surviving 1 bad drought.  For a 3-yr mouse lifespan that survival of 1yr might be 33% for an 80yr human lifespan it might be 1.25%

I just had a delicious burger and wasn’t tempted in the slightest to sneak any Meow Mix from my cat 🤢

Btw cat food is high in ash 👍

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On 10/21/2021 at 6:58 PM, KHashmi317 said:

Hi Clinton!

I've sent an email to Michael Rae, explaining that his earlier debunking of a similar "timed fasting is as good as CR" post, might be good to repost.

If you want to cover your arteries with plaque, by all means, keep eating your burgers.

    --  Saul

 

 

 

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Saul,

 I don’t eat burgers very often,

 I think once or twice a month they’re just fine.  Plenty of vitamin K and a diet rich in tocopherols and tocotrienols from nuts is also beneficial in removing any plaques.  IAC vegans don’t enjoy any increased lifespan and die at the same rate as agnostic meat-eating barbarians - which MR specifically tries to hopefully address and compensate for in his post regarding his supplementation.

 

 

Edited by Clinton

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Nope.  Nuts are good -- but they don't remove plaque.

3 minutes ago, Clinton said:

think once or twice a month they’re just fine.  Plenty of vitamin K and a diet rich in tocopherols and tocotrienols from nuts is also beneficial in removing any plaques.  Vegans die at the same rate as non-vegans, anyways.

You don't have to be vegan to avoid beef.  If you must eat meat, eat one with better lipids -- such as chicken breast.  Better still, eat fish.  That's what I do.

  --  Saul

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Saul,

 I would very much like to see MR’s review and comments on this paper.

 I edited my post at the same time you were replying.

 And yes, chicken and better yet fish would be a better choice than beef, 

by the way- if you are interested I can dig up a very interesting research paper about tocotrienols that … albeit not based on epidemiology on humans and rather theoretical is quite interesting,

Clinton

Edited by Clinton

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Hello;

I'm a longtime lurker finally deciding to register. I'm a tenured non-research college lecturer in business (with a physics background), also known as "Guest" on the longecity forum and did CRON from 2010-2014 before for a variety of reasons switching to a low-meat "normal" diet - still maintaining a BMI of 20-21.

 

This paper is pivoting the IMO still unclear question, of the CR-effect in mice is largely due to fasting. For that it is worthwhile remembering, that fasting in mice is very different than in humans. A mouse undergoing 24 or 48 hours of fasting is demonstrating a very substantial loss in body-weight and increase in autophagy - not paralleled in humans on that schedule.

For example a 72 hour fast in humans lead to a rise of 30% in a common autophagy marker (LC3B-II) in human test subjects:

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102031

In mice autophagy is upregulated much more pronounced; i.e. in this study the same marker is increased by 250%-840% in mice undergoing a 48 hour fast:

https://www.jmcc-online.com/article/S0022-2828(13)00277-0/fulltext

 

There have been prior studies trying to implement a "spread out" CR in mice - but to my knowledge these still left a 12-hour timeframe of "fasting". Of course 12 hours would hardly qualify as "fasting" in human subjects - but given the enormous response of mice in terms of bodyweight and autophagy for 24-hour and 48-hour fasts it is theoretically possible that even 12 hours would lead to substantial response (thus still partly explaining the success of CR in those mice).

 

What I'd therefore like to enquire:

1. Are there CR-studies in mice using a feeding scheme comparable to ad-lib feeding (so no defined 12 hour or longer break)?

2. Are there studies of body-weight loss and autophagy markers in mice undergoing a 12 hour fast (my quick google-search didn't yield any results)? This could indicate, that even in "12-hour feeding" CR-mice a part of the lifespan effect is due to fasting.

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