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Caloric Restriction: Difference between revisions
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== Mechanism == | == Mechanism == | ||
The reasons for the lifespan extension in model organisms through caloric restriction are not yet fully understood. The underlying mechanism of this effect remains unknown. It's possible that the extension of lifespan results from improved health status due to the absence of [[obesity]] and the delayed onset of age-related diseases of the | The reasons for the lifespan extension in model organisms through caloric restriction are not yet fully understood. The underlying mechanism of this effect remains unknown. It's possible that the extension of lifespan results from improved health status due to the absence of [[obesity]] and the delayed onset of age-related diseases of the metabolic syndrome such as cardiovascular diseases and Type II Diabetes mellitus. | ||
Studies conducted with mice suggest that the lifespan extension associated with caloric restriction is not simply a result of leanness caused by calorie restriction. The maximum lifespan of male rats that maintained a low body fat mass through physical activity did not increase, but it did for mice that maintained a low body weight through caloric restriction alone, despite a sedentary lifestyle.{{pmid|17341713}} | Studies conducted with mice suggest that the lifespan extension associated with caloric restriction is not simply a result of leanness caused by calorie restriction. The maximum lifespan of male rats that maintained a low body fat mass through physical activity did not increase, but it did for mice that maintained a low body weight through caloric restriction alone, despite a sedentary lifestyle.{{pmid|17341713}} | ||
Caloric restriction in rats produces soluble factors in the blood serum that cause lifespan extension in human | Caloric restriction in rats produces soluble factors in the blood serum that cause lifespan extension in human cell cultures.{{pmid|25855056}} Various mechanisms are being discussed: | ||
=== Reduction of Oxidative Stress === | === Reduction of Oxidative Stress === | ||
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=== "Reprogramming" of Metabolism and Gene Expression === | === "Reprogramming" of Metabolism and Gene Expression === | ||
According to another theory, long-term reduced food intake "reprograms" the metabolism.{{pmid|17063031}} In mice under caloric restriction, a changed | According to another theory, long-term reduced food intake "reprograms" the metabolism.{{pmid|17063031}} In mice under caloric restriction, a changed gene expression has been observed. On one hand, genes involved in energy metabolism are overexpressed,{{pmid|14688200}} while on the other hand, over 50 pro-inflammatory genes are downregulated.{{pmid|16424110}}{{pmid|19075044}} It's possible that the regeneration of some stem cells is enhanced.{{pmid|24211426}} In some strains of mice, a similar effect can be induced by [[Metformin]].{{pmid|25269675}} | ||
===Increased Formation of Ketone Bodies=== | ===Increased Formation of Ketone Bodies=== | ||
Both caloric restriction and the | Both caloric restriction and the ketogenic diet have therapeutic potential in various animal models of neurological diseases.{{pmid|18845187}} Under caloric restriction, there is a transition from glucose metabolism to the use of ketone bodies. Ketone bodies can be used as an alternative energy source for brain cells when glucose availability is poor.{{pmid|25896951}} | ||
Ketone bodies protect neurons against various types of neuronal injuries. This is one explanation for the beneficial effect of caloric restriction in the animal model of neurological diseases.{{pmid|25896951}} | Ketone bodies protect neurons against various types of neuronal injuries. This is one explanation for the beneficial effect of caloric restriction in the animal model of neurological diseases.{{pmid|25896951}} | ||
=== Increased Autophagy === | === Increased Autophagy === | ||
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 | 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}} | ||
A comparable effect was observed in plants whose lighting was reduced.{{pmid|20021367}} | A comparable effect was observed in plants whose lighting was reduced.{{pmid|20021367}} | ||
=== Reduced Thyroid Hormones === | === Reduced Thyroid Hormones === | ||
Plasma levels of thyroid hormones | Plasma levels of thyroid hormones Triiodothyronine (T<sub>3</sub>), Thyroxine (T<sub>4</sub>), and Thyroid-stimulating Hormone (TSH) were measured in Rhesus monkeys (''Macaca mulatta'') subjected to a 30% CR (caloric restriction) diet. The plasma T<sub>3</sub> level decreased compared to the control group. Given the impact of the thyroid axis on metabolism, this could be a mechanism through which a CR diet mediates its health benefits.{{pmid|12189585}} | ||
==Benefits of Caloric Restriction== | ==Benefits of Caloric Restriction== | ||