Caloric Restriction: Difference between revisions

'''Calorie Restriction''' (CR), also known as '''calorie restriction''' or '''dietary restriction''', refers to a [[diet]] that reduces the intake of chemically bound [[energy]] from [[food]]s by 10 to 50 percent compared to ''[[ad libitum]]'' ("at will") [[nutrition]]. The goal is to achieve a higher [[life expectancy]] or at least delayed [[aging]] or health-promoting effects{{pmid|21663754}}{{pmid|19104499}}, without leading to [[malnutrition]].

In a number of [[model organism|model organisms]], a health-promoting and life-extending effect has been demonstrated through this method. However, no extension of life expectancy has been observed in some species or [[breed (breeding)|breeds]]. The extension of life expectancy in some rodent strains by up to 50%{{pmid|21840335}} is dependent on the [[genome]] and sex among other factors{{pmid|25269675}}.

[[File:Caloric restriction 02.png|thumb|Effects of calorie restriction on the survival rate of laboratory mice (CR=Calorie Restriction).{{pmid|3958810}}]]

[[File:Drosophila melanogaster - side (aka).jpg|thumb|Calorie restriction can significantly increase the lifespan of the fruit fly (''Drosophila melanogaster'').]]

The hormonal and metabolic effects of calorie restriction observed in experimental animals, such as lower body temperature, reduced metabolic rate, and decreased oxidative stress, have also been demonstrated in humans.{{pmid|18729811}}{{pmid|16595757}} Additionally, lower serum levels of basal insulin ("fasting insulin"), profibrotic proteins, various growth factors - such as PDGF and TGF-α - as well as cytokines like Tumor Necrosis Factor-α have been detected.{{pmid|15096581}}{{pmid|17389710}}{{pmid|17093155}}{{pmid|16732018}}{{pmid|16412867}} It is also established that long-term calorie restriction is an effective prevention against Type II Diabetes, high blood pressure, and Atherosclerosis, which together are the main causes of Morbidity, disabilities, and Mortality in humans.{{pmid|19262201}}

There are indications that oxidative stress is reduced by decreased food intake, thereby delaying primary aging. Primary aging is the process in cells and organs that defines the maximum lifespan in the absence of diseases (inevitable aging). Secondary aging is determined by external factors such as diseases, environmental factors, lifestyle, and physical activity (avoidable aging).<ref name="Tostlebe2005">M. Tostlebe: [http://d-nb.info/978638670/34 ''Disproportionalität der Aktivitäten der mitochondrialen Atmungskettenkomplexe im Myokard und in der Skelettmuskulatur im Alter.''] Dissertation, Martin-Luther-Universität Halle-Wittenberg, 2005.</ref> Oxidative stress primarily occurs in the mitochondria, the powerhouses of the cells.{{pmid|19549533}}{{pmid|19634782}} In some mouse strains, the effect of calorie restriction can be partially induced by [[Resveratrol]].{{pmid|25824609}} In yeasts, the protein ''Rim15'', a glucose-inhibited protein kinase, acts as a sensor of nutrient concentrations as well as the initiator of Meiosis and is necessary for lifespan extension in yeasts.{{pmid|24706810}} However, a meta-analysis also reported that caloric restriction – contrary to previous results – does not lead to lifespan extension in yeasts, but the results in yeasts are partly based on methodological artifacts.{{pmid|25071164}}

According to a contrary hypothesis, oxidative stress from reactive oxygen species (ROS) is thought to positively stimulate cell metabolism (Hormesis), which may explain the health benefits of caloric restriction as well as Fasting, oxidative plant compounds in cabbage vegetables, and physical training.{{pmid|16242247}}

Autophagy, also known as “cellular self-digestion”, is a cellular pathway involved in the breakdown of proteins and organelles, and plays a role in various diseases. Dysfunctions in autophagy are associated with neurodegenerative diseases, microbial infections, and aging.

Several indications suggest that autophagy is important for the effects of calorie restriction: The efficiency of autophagy decreases with age; the decline in autophagy is associated with changes in aging biomarkers; the age-dependent change in autophagy is prevented experimentally by calorie restriction; preventing a decrease in autophagy efficiency mimics the effects of calorie restriction; prolonged inhibition of autophagy accelerates the aging process; conversely, prolonged stimulation of autophagy delays the aging process in [[Rat|rats]]; stimulating autophagy can protect older cells from accumulation of altered mitochondrial DNA; stimulating autophagy alleviates age-related hypercholesterolemia in rodents.{{pmid|23331488}}