Does Much of the Life Extension of Calorie Restriction Depend on Length of Fasting?

How much of the improvement in health and extension of life span produced by calorie restriction in mouse studies is due to lowered calorie intake versus length of time spent fasting between meals? In most past studies, calorie restricted mice were fed once a day, resulting in long periods of fasting and hunger-induced metabolic changes between meals. It may be that this timing is important, and of late researchers have started to run studies intended to assess this question.

Data obtained to date strongly suggests that, yes, time of fasting does matter and does contribute to health and longevity benefits in mice independently of reduced calorie intake. Today's research materials further support that conclusion. The authors report on a study in which calorie restricted mice are fed at different intervals. Allowing these mice to eat throughout the day reduces the gain in life span usually observed in calorie restriction studies.

Active phase calorie restriction enhances longevity

Timing feedings to match the active period of the circadian cycle extended the life span of lab mice more than three times as much as caloric restriction alone. Mice that ate as much and whenever they wanted lived nearly 800 days median life span - an average period for their species. Restricting calories but making food available around the clock extended their lives only 10% to 875 days despite restricting calories by 30-40%. Restricting this reduced-calorie diet to the inactive period of the circadian cycle boosted lifespan by nearly 20% to an average of 959 days. Offering the low-calorie diet only during the active period of the cycle extended their median life span to about 1,068 days, an increase of almost 35% over the unrestricted eaters.

Further investigation showed that the mice that lived the longest had significantly better metabolic health, with higher insulin sensitivity and blood sugar stability. They tended to get diseases that killed the younger mice, such as various forms of cancer, at far more advanced ages. Gene expression experiments showed fewer changes in the activity of genes associated with inflammation, metabolism and aging in the long-lived animals compared to the shorter-lived ones.

Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice

Caloric restriction (CR) prolongs lifespan, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour-feeding and 22-hour-fasting, raising the question whether calories, fasting, or time of day are causal. We show that 30%-CR is sufficient to extend lifespan 10%; however, a daily fasting interval and circadian-alignment of feeding act together to extend lifespan 35% in male C57BL/6J mice. These effects are independent of body weight. Aging induces widespread increases in gene expression associated with inflammation and decreases in expression of genes encoding components of metabolic pathways in liver from ad lib fed mice. CR at night ameliorates these aging-related changes. Thus, circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.


So in humans when would be the active cycle vs inactive?

Posted by: august33 at May 13th, 2022 3:49 PM

Given humans' much slower metabolism relative to mice, this means you'd need a very long fast indeed.

Posted by: Mark at May 16th, 2022 6:39 AM

Given the western lifestyle/diet even a modest fasting will bring much heath improvement. For real gains, i would say we have to fast at least 3 days in a row. Preferably 2 weeks every quarter.

I don't follow that advice :)

Posted by: Cuberat at May 16th, 2022 10:17 AM

I think it may be possible to accelerate the benefits of fasting by adding some fairly strenuous exercise to the beginning of a fast when you can. Also, I'm sorry that this study apparently didn't look at several days of no calorie fasting in a row. They probably thought this would be cruel.

Posted by: Thomas Schaefer at May 17th, 2022 4:23 PM

Hi there! Just a 2 cents.

1. Caloric restriction improves health and survival of rhesus monkeys

From this study, rhesus monkeys live average 25 years...and the better ones fare to 35 years; while the maximum specie lifespan is about 41 years old.

35% Calorie Restriction (CR) in young age of monkeys is deleterious - is reduces survival; they die Faster than control unrestricted young monkeys. That is if CR is started at 10 years old..

But, it's when CR is started in Later Mid-Age that it is beneficial...around 20 years old (for them; if they live a maximum of 40 years; then it means they age roughly 3 times faster than humans; and that would mean starting CR, for humans, at 50-60 years old).

When done later, at that late mid-point, then it gives almost 15 years extra; instead of dying at
26 years old, they reach 41 - but not all; only a few of them; thus, it means that CR 'enables' the possibility to 'reach old age' because reduction in damage, better insulin sensitivity, less ROS, less obesity, less inflammation et.c...15 years extra in rhesus monkey - would mean about
35-45 years extra in humans (more than 30; avg 40); so that a person that is 60 years old and starts 35% CR...will live to a 100.
but I'm not so sure about this
and the reason why that...
is the mortality curves;
I mean, it does Reduce mortality - strongly; I mean it reduces mortality by 2.5x - amazing; so you have nearly 3-times less chances of getting Any disease...or dying prematurely...
that means the Effect of CR is very powerful - on health; and of course if you keep your health; you stand (a chance) of reaching Longer Life/ as I was not All monkeys...only a % of them...but many it is 'strong enough'..but it is not 100% clad-proof...some people the effect will be lesser in them...that'S obvious.
But the problem, is the mortality curves...they are almost identical between Control and CR monkeys....I mean yes, Control animal will die much more often much more quicker...But, they Too will reach (a % of them..) the Maximum that the CR reaches; meaning, CR does not Really make animals live longer - rather, it Assures that they Reach their Maximum Potential
but So can a Control monkey - Too; obviously...much less because they have 3x-times more chances of dying; but Some Control monkeys...are Fit...enough..and CR is then useless for them...and asw such they will reach the maximum - Just like Cr that case, CR is redundant and uselless...
So it means, if you are'll get a Big Boost...if you are healthy enough..and not even doing any could be much less worth it (in your case, specifically); it will reduce mortalitly - dramatically (3x); but if you are fit and not doing CR; it becomes redundant; and the effect will be less; Stil...'better safe than sorry...' do it anyway....
but Not in young age ----- people need to start in Older mid age; not from youth...
well...there are some people who ahve done CR ...since basically they are children...and they are fit and healthy...but I don't know...I would be on the cautious and not do extreme CR in children or teens...they Need the food...they are growing, CR is 'taxing' and 'stressing' on the body...
older people in their 30s 40s..50s..or 60s...well it's doable and will yield better results; best - starting at 60.
It's like there is a 'boost' - and this boost needs 'be done late'...and so it 'adds' on the mortality curve...if done's why the rhesus monkeys can then live to 41 years old (only a few of them...but some reach 35 years old).

Just a 2 cents.

PS: Bottom line, do it, but later and be's dire...35% CR can be need to be/get used to that...and Not do this if Very sick(ly) can worsen must get your minerals..proteins etc...and Some calories obviously...starvation is only good up to a point;
'circadian fasting'...they say - stop eating at ...for many hours...then eat - 1 (35% less calories)...and that's it. then fast again for many hours...some people are capable of 'skipping a day' - not eating At all for a day...I did that...but kinda got tired f it...went back on regular daily feeding...but yeah the effect will be stronger if you do skip a day of feeding. You wil keep your heallth better longer....and you give yourself a chance of reaching 100-110-120...
with that said...the fact that mortality curves were Both reaching 41 years...shows that, CR, is a 'nice plus'...but if you are Genetically/Biologically will reach 120 - CR or Not.
This has been shown in Centenarians...some Never did Any CR...and reached centenarian age...but they did eat 'well' and nutriously and even did 'cheat days'..and Even Are Crap --- smoked, ate tons of sweets (which give diabete), bacon, you name it...and They Still reached centenarian CR is just an 'assured/able/enabler' of you reaching their age (if for example, in your family, everybody died before 80-90 years old).

Posted by: CANanonymity at May 17th, 2022 9:24 PM
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