Anti-Aging Measures: Calorie Restriction

The so-called calorie restriction or calorie restriction means a reduction of energy intake through food, in order to achieve in this way a health-promoting and life-prolonging effect. In humans, calorie restriction is able to lower LDL cholesterol, triglycerides, fasting glucose and blood pressure, and improve HDL cholesterol and insulin sensitivity. Other studies-see below-have shown that calorie restriction can also reduce DNA damage, lower insulin and T3 thyroid hormone levels, lower body temperature, and reduce tumor necrosis factor-alpha (TNF-α). One reason for the lower accumulation of oxidation products is primarily the lower radical formation rate, which is due to a lower metabolism and lower oxygen consumption. Furthermore, increased apoptosis (programmed cell death) of premalignant precursor cells (malignant precursor cells) and increased autophagy (see below) can be achieved, for example, by a 12- to 14-hour food abstinence (deprivation of food). The start of programmed cell death is the release of the protein cytochrome c from the mitochondria into the cell interior. For this purpose, the otherwise dense membrane of the mitochondria becomes permeable. After this step, the initiation of apoptosis is irreversible (irreversible) and the cell is degraded. Autophagy serves cellular quality control (“recycling program”). For example, misfolded proteins or damaged cell organelles that could impair the functionality of a cell are eliminated and self-digested (autophagy = “eating oneself”). This process takes place intracellularly. A lack of energy or nutrients (amino acids), leads to a stimulation or increase of autophagy. A recent study found that carbohydrate deficiency also increases autophagy. Both an energy deficiency and a carbohydrate deficiency initiate the sending of a signal via the so-called WIPI4 protein (WIPI: WD-repeat protein interacting with phosphoinositides). This regulates the extent of degradation by autophagy. To date, four WIPI proteins (WIPI1-4) are known to be involved in the regulation of autophagy. Dysregulated or decreased autophagy is present in many age-related diseases such as type 2 diabetes mellitus, tumor diseases, or neurodegenerative diseases. Caloric restriction is also associated with a reduction in mitotic velocity and increased DNA repair. Caloric restriction changes the function of the coenzyme NAD (nicotinamide adenine dinucleotide) – from a digestive enzyme NADPH (nicotinamide adenosine dinucleotide phosphate) becomes a coenzyme of DNA repair! For this purpose, the unreduced NAD dock with the so-called Sir2 (Silent information Regulator/Gene-Silencing) at the DNA and cause there a change of the genetic code (DNA repair). Caution. During abstinence from food, alcohol must not be drunk, because during alcohol degradation the valuable NAD turns into NADH! NAD acts as a hydrogen transfer agent. In interaction with the enzyme ADH (alcohol dehydrogenase), NAD causes alcohol degradation in the liver by oxidizing alcohol to acetaldehyde. The NADH formed during alcohol degradation must be converted back to NAD by other metabolic processes. Many of these above factors represent biomarkers of aging – there is a direct link between these biomarkers and the risk of developing a disease of aging. Diseases of aging include diabetes mellitus, obesity, atherosclerosis (hardening of the arteries), and the so-called metabolic syndrome. In many animal species, calorie restriction has been shown to increase maximum lifespan, e.g. in primates, rats, mice, spiders and the nematode C. elegans. An increase in life expectancy of 30-50 percent could be achieved. Furthermore, the occurrence of malignancies could be reduced. To date, calorie restriction is the only cross-species method of extending both average and maximum lifespan! Energy intake must be minimized, but care must be taken to ensure an adequate supply of vitamins, minerals and trace elements and other important vital substances.Therefore, the difference between calorie restriction and food restriction is that calorie restriction is a form of diet which is rich in vital substances, while food restriction is simply reducing the total amount of food without paying attention to optimal vital substance intake – as is the case, for example, with the well-known FDH diet – “consumption” half.

Study results

Dr. Eric Ravussin of Louisiana State University in Baton Rouge enrolled 48 healthy overweight but not obese men and women in his six-month trial to assess the effects of calorie reduction. The subjects were assigned to one of four groups: 1. a control group that followed a normal diet; 2. a calorie-restricted group that received 25 percent fewer calories than needed daily; 3. a group that exercised and took in fewer calories; and 4. a group that followed a very calorie-restricted diet that started at 890 kcal per day and then increased to achieve a 15 percent weight reduction. Compared to the control group, which lost about one percent of its weight in six months, the two calorie-restricted groups (with or without exercise) were at about ten percent weight loss. The subjects in the very low calorie group even lost almost 14 percent of their weight. The researchers also observed lower blood insulin levels after fasting, as well as lower body temperature in all subjects who underwent caloric restriction. Furthermore, there was less DNA damage in patients with lower calorie intake. According to the results of a study published in the May 2006 issue of the Journal of Clinical Endocrinology and Metabolism, calorie restriction may be more effective than exercise in influencing factors associated with longer life. However, the study does not refute the many positive effects that physical activity has on health and disease prevention. For the study, researchers at Washington University School of Medicine, led by Prof. Luigi Fontana, compared 28 members of the Calorie Restriction Society – whose average caloric intake over the past six years was about 1,800 kcal – with 28 people of predominantly sedentary lifestyles and 28 endurance athletes who consumed a Western mixed diet of about 2,700 kcal per day. Body fat was found to be comparable between the calorie-restricted and endurance sports groups and was lower than that of the predominantly sedentary group. Compared to the other two groups, the calorie-restricted group showed lower levels of the thyroid hormone triiodothyronine (T3) – which affects energy balance and cell metabolism. In contrast, thyroid hormone thyroxine (T4) and TSH (thyroid-stimulating hormone) remained normal. This shows that the calorie-restricted group did not exhibit hypothyroidism. In addition, the calorie-restricted group showed lower blood levels of tumor necrosis factor alpha. TNF-α is a central mediator of the systemic inflammatory and immune response with effects on a variety of target cells (granulocytes, endothelial cells, hepatocytes, hypothalamus, fat & muscle cells, monocytes/macrophages). Lower concentrations of TNF-α serve the physiological defense against infections – for example by bacteria or viruses. The combination of reduced T3 and TNF-α levels may be able to slow the aging process – through the mechanisms of lowered metabolic activity and reduced oxidative damage. A report in the July 2006 issue of the Journal of Biological Chemistry provides further evidence that caloric restriction can be used to prevent (preempt) Alzheimer’s disease. Prof. Giulio Maria Pasinetti, director of Mt. Sinai School of Medicine’s Neuroinflammation Research Center, and his colleagues administered a calorie- and carbohydrate-restricted diet to rats and observed a reduction in so-called amyloid beta peptides, which lead to plaque formation in the brains of Alzheimer’s patients. In contrast, the rats fed a high-calorie, high-fat diet developed an increase in these peptides. In addition, brain levels of SIRT1, a member of the sirtuin protein family associated with longevity, increased in the calorie-restricted rats.SIRT1 may be able to activate an enzyme alpha-secretase, which inhibits the production of amyloid beta peptides. A study by the U.S. National Institutes of Health investigated over two years how healthy people (21-50 years old; body mass index of 22 to 28 kg/m2) responded to a restriction diet of 300 kilocalories per day. As a result, the participants not only lost an average of 7.5 kg in weight (of which 5.3 kg was adipose tissue) over two years, but all cardiometabolic metabolic parameters also improved. Laboratory parameters measured included HDL cholesterol and LDL cholesterol, triglycerides, insulin sensitivity and fasting glucose, and C-reactive protein (CRP). For caloric restriction, see also “Intermittent Fasting.”