Calorie restriction dieting

Calorie restriction dieting

“Review the scientific literature on the effects of calorie restriction on health and longevity”

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Clara Piot          January 2017

201601350        Bioactive Food Components

1. Introduction

Calorie restriction dieting is a reduction of energy intake without malnutrition. This notion appears in the 1930s when it was shown that food restriction and longevity are correlated. In fact, a study (McCay et al. 1935) proved that calorie restriction diet extends the lifetime of rodents, and this increase may reach 50%. Nonetheless, results of this regimen still remain complex because it has many effects on metabolic, neuroendocrine and apoptotic changes according to each organ system and species (J. Koubova et al, 2003). The mechanism of its action remains unclear but it is well known that it prevents from diseases and loss of functionalities caused by aging. Aging acts as a natural process, progressively within the cells, deteriorating their structure and functional capacity in the whole organism. It is led by genetic influence and environmental insults. Improving metabolic pathway and hormonal factors provide benefits to most of the animal models studied. Calorie restriction is the most successful intervention to delay the onset of age-related diseases and muscles weakness (G. López-Lluch et al, 2016). Thus, reducing caloric intake by 20-40% extends lifespan. However, an adequate intake of essential elements and vitamins is fundamental. The aim of this report it is to understand the effects of calorie restriction diet on the health and longevity. The first part focuses on the calorie pathway with the example of the brain response and its effects on cancer. Furthermore, some other examples of health effects are introduced. Finally, some perspectives and remarks pointed out the importance of accomplishing further studies to advance our knowledge in human CR diet and prevent the molecular damage. (S. Fusco et al, 2013)

1. Effect of calorie restriction on the longevity

1. The calorie restriction response

Calorie restriction is an adaptive response triggered by stress. It is an adaptation of the organism in order to survive during hard times. It prolongs life span from yeast to mammals. The longevity promoting results by preventing muscle damage and reverse aging cardiomyopathy. The calorie restriction pathway is described in figure 1.

Overall, CR blocks IGF-I receptor-dependent pathways and target of rapamycin (TOR). It induces the activity of the AMP-dependent kinase (AMPR) and sirtuins which leads the mitochondrial activity. Both TOR inhibition and AMPR activation raise the activity of Forkhead box proteins (FoxO) which induces auto/mitophagy and antioxidant expression. The activation of nuclear factor erythroid 2-related factor 2 (NRF2) that regulates the mitochondria’s transcription induces antioxidants process protein as well.  

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Then, modifications of physiological processes occur such as the decrease of cell proliferation, a reduction of inflammation, changes in mitochondrial physiology and an increase of autophagy and antioxidants expression. This response obtained is related to three factors at least: the numbers of the calories uptake, the quality of the source and the nutritional stress induces by this diet. Some nutrients are more efficient than others, for example, protein/carbohydrate ratio has a significant role on the nutrient sensors. Mitochondrial metabolism is regulated by these nutrient sensors. The CR pathway is a modulation of antioxidant and mitochondrial activity in cells and tissue. Mitochondria are the main cellular oxygen consumers and production site of free radical. Thus, a decrease of free radical production by the mitochondria is observed in the response (G. López-Lluch et al, 2016; A.E. Civitarese et al, 2007). [pic 4]

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Figure 2 : Interaction of mechanisms in the CR longevity effect (G. López-Lluch et al, 2016)

As it is demonstrated on figure 2, the calorie restriction diet lowers the plasma level of IGF-1R, insulin and glucose. Simultaneously, the increase of AMP/ATP ratio leads to activate AMPK, an enzyme energy sensor. AMPK inactivates TOR response and consequently stimulates FoxO action which is a crucial mediator for launch protective mechanisms such as autophagy and antioxidants release. Furthermore, sirtuins is a metabolic sensor in detecting NAD+/NADH fluctuations. NAD+ is accumulating throughout the reduction of nutrient and then triggers sirtuins activity. Sirtuins regulates the metabolism, cell cycle, insulin response, autophagy, etc. For human, the AMPK’s role is surrounding by contradictive studies, and its activity is may be not affected by CR. It is CR procedure-depending. (G. López-Lluch et al, 2016)

1.  The importance of reactive oxygen species (ROS) and the degree of fatty acid unsaturated

Ageing process is related to mitochondrial damage. These destructions induce ROS secretion and at the same time reduce antioxidant defenses. ROS are byproducts of oxidative phosphorylation and interact with proteins, lipids, and DNA. Deterioration pathway of the whole cell physiology, organ, and tissue led to the increase of ROS is described below. Normally, mitochondrial damages are removed by autophagy process. The mitophagy inhibition, links with the aging development, declines the mitochondrial turnover which has a crucial importance.  (A.E. Civitarese et al, 2007)

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Improving energy efficiency induces mitochondrial biogenesis, and in this way, the organism needs less oxygen and produce less ROS. CR acts by modifying saturation/unsaturation index of the mitochondrial membrane. That is how it prevents oxidative damage and maintains membrane fluidity. The fatty acid composition in the cell membrane is another important factor. The aging process increases lipid peroxidation whereas CR increases the peroxidation resistance. The lipid composition of the CR diet significantly impacts the longevity effects as it is illustrated next page. (G. López-Lluch et al, 2016)

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1. Brain response to CR

The brain is the most important effector and regulator in the organism adaptation and health response to CR. Firstly, it fortifies the body by activating survival signals after a moderate physiological stress. Then, signals are integrated into the hypothalamus and inform about the energy store and the availability of nutrients. It activates the neuroendocrine response that modifies behavioral and enhanced higher-order function as learning and memory. In addition, it improves resistance to brain damage and senescence pathology. Some effects have been observed as a change in lipids and glucose in the blood. The higher-order cognitive and behavioral response are linked with the control of the appetite and energy expenditure in the hypothalamus, while hypothalamic centers control metabolic responses in the periphery. Involvement of nutrient sensors in brain area maintains central and peripheral circadian rhythms by coordinating nutrient viability (S. Fusco et al, 2013). Circadian rhythms are any biological process that follows a roughly 24-hour cycle, driven by a circadian clock. This cycle is really important in memory consolidation and it can alter mood if it is not well maintained (W.J. Schwartz et al, 2004).

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