Calorie Restriction & Anti-Aging
The understanding of human aging has long been mechanistic: the body has been equated with a machine that is worn out, in which small damages accumulate and which eventually stops working. At the same time, damage to the genome that occurred during life was held responsible for aging and death.
The successful cloning of mammals corrects this interpretation of the aging process: old cell nuclei are injected into the cytoplasm of an egg cell without a nucleus during cloning, which leads to the conception and birth of a new individual. Despite initially contradictory reports, the lifetime of this clone, whose genetic information is DNA from an adult organism whose lifetime had already partly expired, is not reduced. The telomeres, which are important for the stability of the chromosomes, also showed a youthful length in the experiments. If chromosome damage were responsible for the ageing process, cloning would not be possible. Cytoplasmic factors of the oocyte are obviously able to “reduce” the DNA of the adult individual and restart it. This fact suggests that gene regulation rather than gene structure is altered during aging.
According to current knowledge, ageing is associated with two basic functions of our lives: reproduction and metabolism.
Assuming that the reproduction and rearing of offspring is a major goal of biological life, it is understandable that after the completion of the reproductive functions, aging processes occur more intensively. This can be studied during the development of postmenopausal complaints. If the reproductive phase is postponed, this has – initially temporarily – a life-prolonging effect.
Interventions that slow down the speed of cell division as well as the rate of mitosis therefore have an “age-pushing” effect. The phasewise immobilization of gene segments prolongs the lifespan of low organisms. The molecular biological mechanism responsible for this is gene silencing. In this process, entire parts of chromosomes – and thus the genes on them in blocks – are transcribed. The silencing is triggered by the silent information regulator (Sir). The connection between silencing and aging was recognized by the Sir mutation, which directs the Sir2, -3, and -4 complex from the telomeres to those regions in the genome where ribosomal RNA is formed and immobilized by the Sir. This was associated with an increase in lifetime. But also histone deacetylases, which remove acetyl groups from the lysine residue of histones, prolonged the lifetime.
The ageing process leads to abnormal methylation of the estrogen receptor gene, especially in the mucosa cell of the colon. But the estrogen receptor genes can also be methylated in the vascular wall, resulting in abnormal proliferation of the vascular muscle layer. Estrogens can normally inhibit smooth muscle cell proliferation, but if their receptor is deactivated by methylation, this inhibitory factor is omitted. Estrogen can also prevent the paradoxical effect of acetylcholine, which causes vasoconstriction in the vascular wall. This advantage is also missing if the estrogen does not have an active receptor.
It is known that over-nutrition (resulting in obesity) has a life-shortening effect.
With increased food supply, but also in old age, the activity of certain enzymes increases, which accelerates the aging process.
Calorie restriction seems to play an important role in anti-aging therapy. Since time immemorial, our brain has tried to find ways and means to prolong our lives. Of all the therapeutic interventions that have been presented so far, only one scientifically holds a strategy, namely that of calorie restriction. The very impressive mouse experiments demonstrated that the lifespan of animals under reduced calorie intake could be extended by up to 40%. This study was confirmed by numerous working groups, and it can be assumed that it is also transferable to humans.
Food intake is associated with an energy gain that is possible through electron transfer in the respiratory chain. This provides ATP, the basic energy currency of our organism. Although an abundance of antioxitative systems established themselves in the course of evolution in order to prevent the escape of individual electrons during electron transfer and thus the formation of free radicals, electrons nevertheless escape sporadically and attack the adjacent carbohydrates, fats and amino acids as free radicals. The more energy is taken up by the food, the more electrons can be used in the respiratory chain to generate energy, but on the other hand they can also escape. For this reason, food intake is not only a source of energy, but also a source of free radicals. By reducing calories, the source of free radicals becomes smaller. Calorie restriction can also stimulate protein synthesis genes, as well as those genes involved in gluconeogenesis and the pentose phosphate cycle. At the same time, fatty acid synthesis and nucleotide precursor synthesis are enhanced. Conversely, inducible heat-shock factors and inducible DNA repair systems are suppressed.
Calorie restriction reprogrammes the genes of energy metabolism and protein synthesis. It could be shown that 51 genes could be stimulated by calorie restriction more than twice as much. The gene was stimulated for glucose-6-phosphate isomerase, which induces glycolysis, for fructose-1,6-biphosphatase, which is necessary for gluconeogenesis, and for transketolase. Calorie restriction also induced fatty acid synthase and increased insulin sensitivity by inducing glucose-dependent insulinotropic peptides. The expression of stress proteins and detoxification enzymes was also reduced. An indication that there is indeed a lower cell load due to calorie restriction. Not only can genes be reactivated by food withdrawal, but the radical situation in the body can also be changed. Since free radicals also have growth-reducing effects, it is not surprising that a reduction in metabolism increases scavenger mechanisms and lowers free radicals.
Sleep deprivation can probably also accelerate the endogenous aging process via central factors, especially the occurrence of diabetes mellitus and hypertension. Reduced sleep increases the glucose threshold and at the same time the sympathetic tone. Both are risk factors for the development of insulin resistance and hypertension. If the hormone cortisol increases in the blood in the evening, this is a further indication of age-specific insulin resistance and memory deterioration.
In low organisms, changes in genes involved in reproduction and metabolism can alter lifetime.
In humans, the ageing process also leads to the expression of different genes, the characterisation of which will become even more precise with the implementation of chip diagnostics, which will certainly have a positive effect on possible prevention strategies.
The above-mentioned scientific findings clearly show a common thread: regularity. All organ systems and metabolic activities are subject to rhythm and regularity. I believe that responding to these body needs at an early age is a way to keep the body healthy and vital for a long time.