Calorie Restriction Benefits in Rats Do Not Scale As Expected

Over the last twenty years researchers have undertaken a great many rodent studies of calorie restriction, also known as dietary restriction, and its ability to improve health, slow aging, and extend longevity. As this paper goes to show there is much left to learn, however. In particular, the relationships between degrees of calorie restriction, enhanced longevity, and benefits to particular narrow aspects of health are complex. One of the unexpected outcomes here is that mild calorie restriction has a very similar outcome in terms of life expectancy as that of more rigorous calorie restriction - at least in one particular commonly used laboratory rat lineage. That qualification is necessary, as results have varied over a selection of various lineages.

Given that short-lived species such as mice and rats have far more plastic life spans than long-lived species such as humans, the long-term characteristics of the calorie restriction response when it comes to aging and disease are likely to be quite different for us in many of the important details. Certainly it doesn't extend human life by up to 40% as it does in mice, as that outcome would have been noticed centuries ago at the very least. This is the case even though many of the short-term measures of changing metabolism in response to calorie restriction are similar for all mammals, and it has been shown to result in notable health benefits for human practitioners.

Dietary restriction (DR) has become the gold standard to which manipulations that increase life span and appear to retard aging are compared. DR has been shown to increase life span and reduce or delay the increase in age-related pathologies and the decline in most physiological functions in numerous genotypes of laboratory rodents. DR increases the life span of a wide variety of other organisms. These data have led to the view that the effect of DR on longevity and aging is universal, a view that was reinforced in 2009 with the first data showing that DR significantly decreased the incidence of age-related deaths and delayed the onset of age-related pathologies in rhesus monkeys. The universality of the effect of DR on longevity was called into question in 2010 when researchers reported the effect of DR on approximately 40 different recombinant inbred lines of male and female mice. Surprisingly, approximately one-third of the mice showed a decrease in life span on the DR diet; one-third showed no effect of DR on life span; and only one-third showed the expected increase in life span.

One possible explanation for the recent contradictory data on DR is that the level of DR required to increase life span is genotype dependent, and because the previous studies used only one, relatively high, level of DR, which might have had a negative effect (instead, lower levels of DR might increase life span). The standard DR diet that is usually used in DR rodent studies one in which rodents are fed 60% of the diet consumed by animals fed ad libitum (AL) (i.e., 40% DR). This is the level of restriction used by the National Institute on Aging (NIA) for their aged rodent colonies, which have been available to investigators studying aging. It is generally believed that the increase in life span is directly related to the level of DR, that is, increasing the level of restriction leads to a greater increase in life span up to a certain point (e.g., around 60% DR) where further restriction is harmful. However, there are only limited data to support this view.

The purpose of this study was to determine whether a modest level of DR (10% DR) could increase the life span of male F344 rats and compare its effects on life span and pathology to the effects of 40% DR. We found that 10% DR significantly increased mean life span, and surprisingly, the increase in mean life span obtained by 10% DR was similar to that observed with 40% DR. However, we observed differences in the effects of 10% and 40% DR on the incidence of fatal neoplasia; 40% DR resulted in a significant reduction in fatal neoplastic diseases, especially leukemia, which was the most common neoplastic disease in the rats.

Link: http://onlinelibrary.wiley.com/enhanced/doi/10.1111/nyas.12982/

Comments

Hi and Merry Christmas!

Who knew I would be doing CR on Christmas day, when in the old times it was all about stuffing of one's self with really 'good' fat stuff. After the holidays, you would pack on 10 lbs extra and hope to do not die from the frivolous feed orgy. Not these holidays, CR shall be part of new christmas time. Moderation is key but clearly people (from another website suggesting to drop those hings and the uninamous angry comments) don't want to be taken off their bacon, ham, eggs, turkey, pies, mcdo's, burker king, donuts, maple syryp and Coca-Cola.
These things can be consumed with moderation, during holidays, but if you are unhealthy, just don't, CR may save your life and still be here for a next Christmas.

Just my opinion, this study shows that there is two 'general' pathways to aging: Inflammaging (pathological aging by inflammation/pathologies formation/senescent cell inflammation accrual vicious circle) and Intrinsic Aging.
Inflammaging is a vicious feed circle of unstability of the gene network. Intrinsic Aging is a normal aging process of slow accumulation, but constant, of damages and loss of genome telomeric DNA from damages incured of normal cell metabolism. Mainly, random dna damages, oncongene-induced damages and replication end-problem damages. Intrinsic Aging is the first one and the Inflammaging is the second one, the first one never goes away, and is omnipresent, but second one can when gene network stability/integrity/transcription fidelity is regained.

We can infer these 2 main pathways, in order of precedence, because unhealthy people can die from diseases much more before their maximum lifespan; yet, vert healthy people who, are almost never ill, one day die too,
before or at maximum lifespan. Studies are currently concentrating on slowing pathological inflammaging for urgence to save unhealhy sick people. Later on, when we are all healthy (perhaps utopic), we must focus on first intrinsic aging, because we are not out of the woods yet, we are only concentrating on that secondary form of aging. If we want to surpass MLSP, intrinsic aging studying and curing is the only way.

I am not surprised one bit to read that CR wether little, mild or extreme does not make That much difference in terms of lifespan in this study here. It's all about a careful balance between nutrient deprivation, nutrient density/condensation per molecule in food per glucose molecule, type of carbs, type of fiber, type of protein , type of minerals and many other small details nutrient wise. Extreme nutrient deprivation (40-60% CR) nearing starvation can be detrimental, that's why 10% CR can still do good 'health' effect. It's not so much calorie content, it is nutrient composition that determines CR effect. As seen from AGEs study that show calorie content can overridenn by AGEs content per molecule in food. Calories accelerate AGEs formation, but there is difference between 'empty calories' and 'nutrient-dense calories'. When you start adding elements that alter glucose metabolism and fat metabolism; it is bound to affect CR and AGEs accumulation, in concert with calorie count. Still, the final message being on lighter note, don't overdo it today, on this christmas day, eat moderately, for sasiety but don't overindulge too much in the good christmas spirit stuff. CR will improve health (as seen in ape study reduction of mortality..very telling) and make possibility to reach 100 perhaps (genetics will overide CR, as I have family who did basically 10-20% CR and never made it past 75 either..genes predisposition decided so. That is a reason and imperative to study intrinsic aging when we finally end diseases).

Posted by: CANanonymity at December 25th, 2015 10:16 AM

From all I've read it seems anyone interested in LE shouldn't be doing more than mild/moderate CR. Severe CR is dangerous no matter how careful you track things or how much think you understand it.

Posted by: KC at December 30th, 2015 12:55 PM

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