Caloric Restriction: Difference between revisions

=== Reduction of Oxidative Stress ===

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.<ref name="PMID19549533">A. Csiszar et al.: ''Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1.'' In: ''Mech Ageing Dev'' 130, 2009, pp.&nbsp;518–527. PMID 19549533.</ref><ref name="PMID19634782">J. Skrha: ''Effect of caloric restriction on oxidative markers.'' In: ''Adv Clin Chem'' 47, 2009, pp.&nbsp;223–247. PMID 19634782.</ref> In some mouse strains, the effect of calorie restriction can be partially induced by [[Resveratrol]].<ref name="PMID 25824609">PMID 25824609.</ref> 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.<ref>S. Nagarajan, A. L. Kruckeberg, K. H. Schmidt, E. Kroll, M. Hamilton, K. McInnerney, R. Summers, T. Taylor, F. Rosenzweig: ''Uncoupling reproduction from metabolism extends chronological lifespan in yeast.'' In: ''PNAS.'' Volume 111, Number 15, April 2014, {{ISSN|1091-6490}}, pp.&nbsp;E1538–E1547, [[doi:10.1073/pnas.1323918111]], PMID 24706810, {{PMC|3992631}}.</ref> 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.<ref>25071164</ref>

===Hormesis===

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.<ref>PMID 16242247.</ref>

In contrast to the free radical theory, it is assumed that an increased formation of reactive oxygen species in the mitochondria, associated with caloric restriction, causes an adaptive response that enhances stress resistance.<ref name="PMID20350594">PMID 20350594</ref>

===Activation of Sirtuin-1 and Reduced Expression of the mTOR Receptor ===

Signal-regulating enzymes such as [[SIRT1|Sirtuin-1 (Sirt1)]] in mammals, or [[SIRT2|Sirtuin ''Sir2'']] in yeasts, may play a role.{{pmid|25349818}} The cells of calorically restricted test animals produce Sirt1 in larger quantities.{{pmid|19713122}} An increased production of Sirt1, in turn, reduces the expression of the mTOR receptor (''mammalian Target of Rapamycin''),{{pmid|20169165}} which is also associated with the aging process. The lifespan of mice can be significantly extended by administering [[Rapamycin]], which docks to the mTOR receptor.{{pmid|20331443}}{{pmid|19587680}} [[Melatonin]] is also being studied due to its activation of Sirtuin.{{pmid|25824609}}

=== "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 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===

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}}