Introduction
If we had the opportunity, we all want our body to stay in top shape as long as possible. In old age, we would certainly be able to move freely, to keep our intellectual sharpness, to keep our senses sharp and much more. The dream of defeating age has been around since the beginning of human civilization; Most of our history, however, it was reserved for the area of divine and supernatural. Recently, with the upswing of age research as a scientific field, there is hope of transforming this dream into a tangible reality. To the extent that we begin to understand the biological relationships behind the slow but constant reduction in our body, we also gain insights into potential therapies and treatments that slow down, stop, stop or reverse one day. So why are waiting for the development of these anti-aging treatments if we can already improve our longevity by changing certain aspects of our lifestyle? In this article we present science behind the most important factor for slowing down the aging process, namely our diet, and how we can optimize it to extend our life expectancy.
About epigenetics
Epigenetics is generally defined as the examination of inheritable changes in the phenotype, which are not related to changes in the DNA sequence and are usually due to changes in gene expression. The following question arises: If all cells in our body have almost exactly the same genetic information, how does it come that a skin cell differs so much from a liver cell or a neuron? Why can one do so many things that the other cannot do? It turns out that they contain all the same information, but use it in very different ways. Of the approximately 20,000 genes in the human genome, only a small part is "expressed" at a certain point in time. h. rewritten in RNA and then translated into proteins. Therefore, it is this pattern of gene expression that determines what function every cell has, whether it is replicated and so on.
This expression pattern is not only different from cell type to cell type, but the same cell can also experience changes in gene expression (i.e. epigenetic modifications) over time. The latter are generally determined by internal regulatory mechanisms and by environmental factors, including our diet. These are these changes that contribute to the age of our body over time [1]. Epigenetic changes occur mainly in the form of chemical changes, either on the DNA itself (mostly in the form of DNA methylation) or on the histones, the proteins that the DNA is wrapped around (which are usually acetylated or methylated).
The role of epigenetics in aging
The mechanism, which is based on the aging process, is quite complex and includes many elements that interact with each other. He was in a work published in 2013 in the magazine Cell with the title "The Hallmarks of Aging" [2] described in great detail, and the individual processes described there that contribute to aging are largely recognized by the researchers in this area. There are now 12 such characteristics. Some are relatively independent of the others (e.g. the loss of proteostasis, i.e. the increase in misconfled proteins or protein unit in the cell), others are more connected (e.g. the decline in the number of stem cells and the accumulation of Senescent cells);
The effects of calorie restriction on aging
It turned out that with regard to the effects of our diet, epigenetics and aging not only depend on what we eat, but also how much we eat. One of the best examined diets in connection with aging research is calorie restriction (CR for Caloric Restriction in English). The connection between CR and an extended lifespan was empirically demonstrated in a variety of animal models, and many of their health benefits were also found in human studies [3,4]. The reasons for the CR-induced slowdown of aging are far from fully clarified, but it has been shown that they are at least partially related to epigenetics. A variety of genes that are connected to age-related processes such as telomerial maintenance, cellular senescence, DNA repair and genome stability are modulated by epigenetic changes according to CR diets [5,6,7].
Epigenetic watches
A highlight of this new biomarker is the recent advancement of epigenetic watches as instruments for measuring biological age, which are currently considered the best instrument of this kind due to its strong correlation with chronological age and overall mortality [8]. Although there are some differences between them, all epigenetic watches are based on the DNA methylation status of a certain group of CPG dinucleotides. The most important models are currently used:
- Horvaths watchthat measures 353 CPGs from DNA samples from any tissue,
- The watch from Hannumthat measures 71 CPGs from thoroughbred DNA samples,
- Levine's phenogage clock, which, in addition to DNA methylation, also takes into account clinical factors such as glucose or C-reactive protein levels or the number of white blood cells, and finally,
- Grimagein addition to the DNA methylation values, which also takes into account lifestyle elements such as smoking [9,10,11,12].
Epigenetic modifications
CR and their anti-aging effects, which are generally defined by 20-50 % without changing the macronutrient composition, as reducing the calorie intake by 20-50 % without changing the macronutrient composition are a topic that we have already briefly addressed in the last article. We would like to further deepen the points mentioned there by concentrating on the three main categories of the epigenetic signatures that are influenced by CR:
a. DNA methylation
The attachment of methyl groups to nucleotides, especially on cytosine residues within CPG dinucleotides, is considered the most important and therefore best documented epigenetic marker. It is known that the degree of methylation decreases with increasing age, while certain genome regions, especially gene promoters, are hypermethylated [13,14]. The hypermethylation of these promoter regions was in turn associated with the gene silencing [15].
A study carried out on cell lines of man and mouse has shown that the effects of CR on the transcriptomic profile through the different expression of the GES Sirt1 (Sirtuin-1) are imparted, a histone deacetylase that, according to this study, could also play an indirect role in DNA methylation profiles; This conclusion is also confirmed in other studies that do not concentrate specifically on CR [16,17,18]. Interestingly, the DNA methylation changes conveyed by CR seem to be continuing long after returning to normal calorie intake; This result is supported by documents from both mouse models and by people who were subject to a famous famine [19,20]. The effects of CR on the biological age were examined on the basis of blood samples from participants in the Calerie study, with a significant slowdown of the aging process based on the Dunedinpace clock [21,22].
b. Mirnas
This type of epigenetic markers are small non -encoding RNAs that modulate post -transcriptional gene expression by either suppressing the translation or triggering the dismantling of the mRNA [23]. Although this has not yet been proven in humans, there are indications that CR has significant health benefits in mice and rhesus monkeys and increases biomarkers against aging. This was documented for various tissue types, including skeletal muscles, vascular endothelium, brain and colon [24,25,26,27].
c. Post -translational histone modifications (Pthms)
The last major category of epigenetic modifications consists of chemical changes to histones, the proteins that the DNA winds around. These modifications usually include methylation, acetylation, ubiquitination and phosphorylation. The resulting consequences are complex and differ depending on the modified histone, the modified rest and the exact type of modification, but usually occur in the form of transcription or suppression of certain genes or genes [28].
With regard to the slowdown of the aging process, it is assumed that the most effective type of PTHM is the deacetylation of lysin residues by a family of enzymes called Sirtuin29]. A study has shown in particular that the Sirtuin Sirt1 was carried out in a vitro simulation of CR-like conditions, which was carried out on human lung fibroblast cultures, in which histoneacetylation and methylation is involved, which causes a chromatin structure of the P16 promotor. This promoter in turn suppresses the expression of P16ink4a, which is known as the trigger of the cellular senescence [30]. Similarly, it was shown that the regulation of Htert, a gene that is involved in the maintenance of telomeres and oncogenesis, is partially caused in human Wi-38 fibroblast cultures under the same simulated CR conditions by histone modifications [31]. Other age-related histone modifiers were documented in CR studies on yeast and mice, including NAT4 and Histon-Deacetylase 2 [32,33].
The "Epigentic Diet"
As far as the quality of our diet is concerned, it is more difficult to separate facts from fiction, but there are a handful of compounds whose geroprotective effects have been proven by published data. The so -called "epigenetic diet" [34] Contains foods that are rich in connections or classes of connections that promote the epigenetic maintenance of important anti-aging markers. To name just a few:
- Polyphenol are of course found in plants (e.g. curcumin in turmeric, resveratrol in grapes, EGCG in green tea) that are involved in the fight against tumor and the prevention of age -related metabolic changes [35,36];
- Sulforaphane, a connection that occurs in cross -flowers (broccoli, kale, cabbage, etc.) is associated with antioxidant and anti -inflammatory effects and the prevention of neurodegenerative diseases [37];
- Spermidine, Whose sources, etc. are mature cheese, mushrooms and soy products, its anti-aging effect of promoting autophagy (i.e. the elimination of cells) owes it38].
Of course, we should also mention what we should avoid in our diet: A recently carried out study has shown that alcohol has a potentially old -fashioned effect by shortening the telomeres that can be reduced the number of divisions that our cells can go through [39].
Conclusion
The area of aging research is becoming more important, and numerous anti-aging treatments are already in clinical testing [40]. However, it is not foreseeable how long these attempts will take or how many of them will successfully come onto the market (if at all). That is why lifestyle factors such as nutrition, movement, stress, etc. are the best way to increase our opportunities as long as possible, and we hope that the guidelines above will offer you a good starting point to acquire more knowledge about this goal.
