A Selection of Calorie Restriction Research

There certainly is a great deal of published work coming out on calorie restriction and the related regulation of metabolism for greater health and longevity; funding for development based upon this field over the past year or two has no doubt further accelerated basic research. For all that I feel this ongoing metabolic examination and manipulation - aimed at slowing rather than repairing aging - is not the best path forward, it is still interesting work. Here are pointers to a couple of recent papers:

Ruminations on dietary restriction and aging:

Calorie restriction has been known for many decades to extend the life span of rodents. Since the more recent discovery that a long-term reduction in nutrient intake also extends life span in nearly every invertebrate model organism used for aging research, the mechanisms behind the longevity benefits of this intervention have been under intense scrutiny. While models have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction remain controversial, resulting in great anticipation of mammalian studies testing these models.

Metabonomic Investigations of Aging and Caloric Restriction in a Life-Long Dog Study:

Long-term restriction of energy intake without malnutrition is a robust intervention that has been shown to prolong life and delay age-related morbidity. A 1H NMR-based metabonomic strategy was used to monitor urinary metabolic profiles throughout the lifetimes of control-fed and diet-restricted dogs. ... This analysis allowed the metabolic response to two different physiological processes to be monitored throughout the lifetime of the canine population and may form part of a strategy to monitor and reduce the impact of age related diseases in the dog, as well as providing more general insights into extension of longevity in higher mammals.

I mentioned the canine calorie restriction study a couple of days ago at the Longevity Meme; the calorie restricted dogs lived two years longer, on average. A more informative article for the layman turned up yesterday in the Economist, illustrating the thrust of the research in terms of metabolic rates and bacterial processes:

Choline is made available for absorption from the intestine by the activities of the gut bacteria that are liberating it for their own purposes. The amount of aliphatic amines in urine is thus an indirect measure of how much choline is available. As in the case of creatine, this differed between the two groups. Dogs on the restricted diet had lower levels of the amines in their urine than did their well-fed counterparts - implying that less choline was being made available. And if less choline were available, that would limit a dog's ability to metabolise fats, and thus restrict its metabolic rate.

The apparent drop in choline levels was much greater than could be accounted for by a relative lack of food, so Dr Nicholson suspects that the restricted diet was also causing the composition of the dogs' gut flora to change in a way that did not favour choline-munching bugs.

Moving on, a couple more papers further reminding us that calorie restriction makes a difference for most age-related conditions:

Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD ... We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.

Different gene expression of skin tissues between mice with weight controlled by either calorie restriction or physical exercise:

Cancer prevention by weight control via dietary calorie restriction (DCR) and/or exercise has been demonstrated in animal models. To understand the underlying mechanisms, we compared phorbol ester (TPA)-induced gene expression profiles in DCR- or exercise-treated mouse skin tissues. SENCAR mice were randomly assigned to one of the following groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AE), exercise but pair-fed at the amount of the control (PE), and 20% DCR.


The results of 22 cancer-related gene expression patterns, especially for certain oncogenes, further supported that PE appeared to be a better alternative than AE to DCR-like cancer prevention. The impact on gene expression pattern was associated with the effect on weight loss (i.e., DCR >> PE > AE). Overall, this study demonstrated for the first time that weight control via decreasing energy intake or increasing energy expenditure resulted in the different modes of gene expression. DCR showed profound inhibitory impact on the expression of genes relevant to cancer risks. Furthermore, exercise along with limited calorie intake appears to be a better method for reducing weight and cancer risk compared with exercise alone.

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"Calorie restriction has been known for many decades to extend the life span of rodents ... While models have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction remain controversial, resulting in great anticipation of mammalian studies testing these models."

So you aren't aware that rodents are mammals!?


Posted by: Mic at April 17th, 2007 11:08 AM

The researcher is referring to more recent work designed to prove or disprove specific theories of biomolecular mechanisms responsible for the benefits of calorie restriction, rather than whether it works. We know it works in mammals, but we don't really know for sure why it works in mammals - the next few years of work are focused on that investigation.

Posted by: Reason at April 17th, 2007 7:02 PM
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