Caloric restriction: the defence against aging
Worried about getting old? It's simple. Eat less and you could live longer. That's the view held by an increasing number of people around the world, with the Calorie Restriction Society one of the main standard bearers. These beliefs are based on extensive research on such species as yeast, fish, rodents and dogs, which suggest that caloric restriction (CR) can slow aging and reduce the incidence of disease, ultimately prolonging life.
Rodents maintained on a reduced calorie intake of 30-40% had an extended life span of 30-50% and reduced incidence of type II diabetes, oxidative stress and neurodegenerative disorders, so it is easy to see why the regime is attractive to humans. However, there are currently no indications that the same effects will apply to humans although research is under way on non-human primates.
CR should not be confused with regular weight loss diets. In fact, weight loss is regarded as a side effect, not a goal. The main objective is to achieve a longer and healthier life by eating fewer calories, while maintaining a regular balance of vitamins, minerals and other essential nutrients.
Following this diet brings about a reduction in the white adipose tissue mass and this has been proposed as a principal factor in longevity. Aging itself tends to have the opposite effect, increasing adipose tissue stores and insulin resistance and this is where clarification is needed. What are the effects of CR and how do they relate to those of aging?
Aging versus caloric restriction: proteomics separates the effects
One way to compare the effects of aging and CR is through the use of proteomics and this approach was adopted by scientists in Spain. Adamo Valle, Jordi Sastre-Serra, Pilar Roca and Jordi Oliver from the University of the Balearic Islands, Palma de Mallorca, studied the protein profiles of white adipose tissue of rats. One set was maintained on a 40% CR diet from age 12-24 months, with a second age-matched set fed ad libitum (AD).
Proteins were extracted from the white adipose tissue and separated by 2D gel electrophoresis and their abundances were compared using image analysis following staining with a fluorescent stain.
An average of 800 protein spots were observed on each gel, with 80-90% matched between the gels in each set. Of these, a total of 133 proteins were found to be differentially expressed between the CR and AD animals.
Many of the CR-induced changes were unaffected by age, implying that CR does not simply arrest or reverse age-associated changes. The influences of the two processes appear to operate under different mechanisms. This was confirmed by identifying 57 of the 133 proteins by mass spectrometric techniques.
The pathways influenced by caloric restriction
The proteins altered by CR were associated with several different cycles, including the glucose and lipid metabolic pathways, which were consistent with increased lipid biosynthesis. The expression of proteins involved in the production of oxalacetate and NADPH and in lipolysis and lipid biosynthesis was enhanced. In addition, certain insulin receptors were also increased by CR which was consistent with a higher response to lipogenic stimuli.
Other protein expression changes induced by CR gave improved protection against oxidative stress by halting the age-associated reduction in the levels of several antioxidant enzymes and decreasing the levels of stress-induced proteins. This observation was supported by a measured decrease in the amounts of carbonyl groups and oxidative adducts.
Both CR and aging also changed the expression of proteins involved in the cytoskeleton, iron storage and energy metabolism, as well as other proteins with currently unknown functions in adipose tissue.
The CR-induced changes are in line with reported microarray studies and will help to understand the molecular mechanisms behind the lifetime extension and the suppression of the effects of aging.
In the long term, the results could also lead to the identification of novel biomarkers of aging and possible targets for mimetics of CR that could provide the same outcome, an extended lifespan, without having to follow a rigorous and controlled diet.
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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