A Few Recent Publications in Calorie Restriction Research

The practice of calorie restriction involves eating fewer calories while still obtaining optimal levels of dietary micronutrients. This results in extended healthy life spans and extended maximum life spans in near all species tested to date, though the data is currently inconclusive for primates, and it is expected that the extension of life span in long-lived animals such as humans will be much smaller than that observed in short-lived animals such as mice.

From an evolutionary perspective, the response to calorie restriction is thought to have arisen as an protective adaptation for the existence of short-lived famine conditions. The length of natural reductions in food supply due to weather, seasons, and so forth, is the same whether you are a man or a mouse - so mice evolved a comparatively long life extension (up to 40% or more) while humans are probably left with just a few additional years. If we did have the ability to extend our lives by decades through eating less, you can be certain that this would have been discovered long ago and be a well-known phenomenon.

Interestingly the effects of calorie restriction on general health and metabolism in primates and mice are very similar despite the large divergence in expected outcomes for longevity. Calorie restriction is just about the best presently available methodology for ensuring good long-term health, and the data from human studies is eye-opening. You should definitely look into it if not already practicing.

Here are some recent publications from the calorie restriction research community, just a cross-section of recent research that caught my eye while browsing. This is fairly low-level work, scientists digging into details in search of new lines of research to pursue.

What are the roles of calorie restriction and diet quality in promoting healthy longevity?

Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan.

Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cancer. Moreover, CR opposes the expected age-associated alterations in myocardial stiffness, autonomic function, and gene expression in the human skeletal muscle. However, it is possible that some of the beneficial effects on metabolic health are not entirely due to CR, but to the high quality diets consumed by the CR practitioners, as suggested by data collected in individuals consuming strict vegan diets.

Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver

Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups.

Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone.

In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.

Thermoregulatory, cardiovascular, and metabolic responses to mild caloric restriction in the Brown Norway rat

Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known about the regulation of CR-induced hypothermia as a function of the circadian cycle. We assessed how mild CR that resulted in a 10% reduction in body weight affected the 24 h patterns of Tc as well as heart rate (HR) and motor activity (MA) of the Brown Norway rat.

Telemetered rats were allowed to feed for 20 weeks ad libitum (AL) or given a CR diet. Tc, HR, and MA of CR rats exhibited nocturnal reductions and diurnal elevations, opposite to that of AL rats. The effects of CR appeared to peak at ~4 weeks. Metabolic rate (MR) and respiratory exchange ratio (RER) were measured overnight after 18 weeks of CR. MR and RER were elevated markedly at the time of feeding in CR rats and then declined during the night.

We found that the pattern of Tc was altered with CR, characterized by elimination of high nocturnal Tc's typically observed in AL animals. In terms of mechanisms to prolong life span in CR animals, we suggest that the shift in the pattern of Tc during CR (i.e., elimination of high Tc's) may be as critical as the overall mean reduction in Tc. Future studies should address how the time of feeding may affect the thermoregulatory response in calorically restricted rats.

Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial activation in discrete regions of the hypothalamus and the subfornical organ

Calorie restriction (CR) has been shown to increase longevity and elicit many health promoting benefits including delaying immunosenescence and attenuating neurodegeneration in animal models of Alzheimer's disease and Parkinson's disease. CR also suppresses microglial activation following cortical injury and aging.

We previously demonstrated that CR attenuates lipopolysaccharide (LPS)-induced fever and shifts hypothalamic signaling pathways to an anti-inflammatory bias. The current study investigated regional changes in LPS-induced microglial activation in mice exposed to 50% CR for 28 days. Exposure to CR attenuated LPS-induced fever, and LPS-induced microglial activation in a subset of regions [and] microglial activation [was] positively correlated with body temperature.

These data suggest that CR exerts effects on regionally specific populations of microglia; particularly, in appetite-sensing regions of the hypothalamus, and/or regions lacking a complete blood brain barrier, possibly through altered pro- and anti-inflammatory signaling in these regions.


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