Operating to achieve caloric restriction effects,

Resveratrol Slows Down
the Aging Process

And joins MCTs as an important nutritional diet mimetic

By Will Block


Compliance is difficult with CR because of severely reduced caloric consumption.
Dietary interventions such as caloric restriction (CR) extend lifespan and health span. Recent data from animal and human studies indicate that CR slows down the aging process, benefits general health, and improves memory performance.

CR also retards and slows down the progression of different age-related diseases, such as Alzheimer’s disease (AD). Yet the specific molecular basis of these effects is unclear. A better understanding of the underlying pathways of these effects could shed light on novel preventive or therapeutic strategies.

CR Mimetics May Achieve Similar Benefits of CR

In a very recent review,1 researchers set out to better understand the mechanisms and effects of CR on aging and AD. They focused in on a potential alternative to CR as a lifestyle modification, what are known as CR mimetics. These compounds—of which not many have been identified—mimic the biochemical and functional effects of CR without the need to reduce energy intake. Among the most investigated mimetics, resveratrol and rapamycin have been shown to effect on aging and possess potential as AD therapeutics.

Thanks to Durk Pearson & Sandy Shaw, we know that MCTs may also operate as CR mimetics in part for the following reasons (see “MCTs and the Ketogenic Diet” in the May issue):


Caloric restriction also retards and
slows down the progression of
different age-related diseases, such as
Alzheimer’s disease.


“ … a very recent paper,[2] in which the researchers show that caloric restriction (CR) in mice causes a shift in energy use from glucose to ketone bodies that keep the brain supplied with energy. The old CR animals show a preservation of white matter integrity as well as long-term memory. The researchers used white matter structural connectivity in the corpus callosum as an indicator of structural integrity. The results revealed that calorie restriction caused a switch from cellular use of glucose as a fuel to ketone bodies (produced from fats), presumably (the authors suggest) due to the decreased glucose available in the restricted diet. These data support the notion that ketone bodies may mimic the effects of caloric restriction. (Emphasis added)”

There is other evidence (see Durk & Sandy’s continuation of their “MCTs and the Ketogenic Diet” article in this issue; see page 21).

A Better Understanding of Diet and Aging

Owing to aging populations and the growing prevalence of neurodegenerative diseases, a better understanding of how changes in diet and dietary regimes can be extremely valuable. This could help identify genes and pathways relevant for human preventive or therapeutic applications, and that would be of major social and economic significance.3


Due to the demanding nature of a CR
diet, caloric restriction mimetics
(CRM) drugs are an attractive
alternative.


Nevertheless, some considerations need to be taken into account. In most of the research, CR animals are compared to AL-fed (ad libitum: letting the lab animals eat as much as they want) counterparts, the latter of which might not represent the best control group because they have the tendency to overeat and become overweight. They lack mental and physical activity, whereas CR rodents tend to search actively for food in their environment, which provides mental and physical activity.

A second concern is compliance with a CR diet in humans, which is very difficult to achieve over a long time. Then, malnutrition is a common problem in older individuals, and a balanced diet is extremely important. Due to the demanding nature of a CR diet, caloric restriction mimetics (CRM) drugs are an attractive alternative.

These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. In the current review, the researchers significantly focused on two molecules that might delay aging and treat AD, which are, as you already know, resveratrol and rapamycin.

But it is still unclear how these molecules exert their effects, and whether their effects are only beneficial is controversial; this is especially true for rapamycin.

In summary, while both rapamycin and resveratrol provide interesting opportunities for novel preventive and therapeutic strategies, resveratrol has fewer side effects and is a nutrient and not a drug, as is rapamycin. Because CR affects several pathways through complex mechanisms, it is logical to assume that several CRMs may need to be used simultaneously in order to mimic the complex effects of CR. Could these be resveratrol and MCTs?

References

  1. Van Cauwenberghe C, Vandendriessche C, Libert C, Vandenbroucke RE. Caloric restriction: beneficial effects on brain aging and Alzheimer’s disease. Mamm Genome. 2016 May 30. [Epub ahead of print] Review. PubMed PMID: 27240590.
  2. Guo J, Bakshi V, Lin AL. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice. Front Aging Neurosci. 2015 Nov 13;7:213.
  3. Wood SH, van Dam S, Craig T, Tacutu R, O’Toole A, Merry BJ, de Magalhaes JP. Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging. Genome Biol. 2015;16:285.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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