Continued 5. Parts of Autophagy vs. mTOR

So back to the topic, I hope everything fits in here. Where were we? Oh yes, we tried to answer this one big question:

** What's the best strategy to balance mTOR and the cellular packman (autophagy)? **

Granted, I've never done it so consistently, as you might assume. It's not that seldom that I give up in the face of little sins emerging occasionally, but of course, I'm also looking more and more (I'm in my mid-30s) for a more meaningful lifestyle. First of all, it is absolutely decisive how old you are and how your fitness and family background looks like. Fortunately, for example, in my family, no case of cancer, obesity or neurodegenerative diseases is known. For this reason, I may have a different approach to the whole thing compared to people who are genetically predisposed to the such diseases. If you are currently suffered by a serious illness or are in danger of getting any health problems in the foreseeable future, it is absolutely necessary to talk to your doctor about any change in your diet or lifestyle. In any case, a doctor should accompany you or at least regularly check certain parameters such as blood lipid levels, blood sugar levels, blood pressure etc. Do not do any experiments just because you read something somewhere. This applies to this article as for everyone else. But healthy people should also keep an eye on their health and, if necessary, consult a knowledgeable person. I can only tell you here how I assess the matter, what I've researched on the subject and how I might implement it. But you always have to keep in mind, especially in biology, that the complexity of biochemistry is not completely understood yet. Moreover, everybody reacts differently and that a lot of (vaguely expressed) controversial data are on the way.

In her book Glow15 the author Naomi Whittel describes how to implement autophagy in the daily routine. And even though I do not agree with some of her findings, I think the book Glow15 is a good guide on this subject. The following suggestions are meaningful to me and might be integrated in your life without any trouble:

                  1.    Natural and healthy food 

We have already discussed these aspects sufficiently. So, please check the first part of the fifth article again. Nevertheless, I will briefly summarize this with further information at the end of this article again.

                  2.    Intermittent Fasting

In my opinion, intermittent fasting makes perfect sense simply because it temporarily reduces the nutrient surplus in your body and therefore gives your packman the opportunity to do his work without being disturbed by "The Ghosts". I have no idea how intermittent fasting is truly implemented and probably are different approaches possible. Me for my part, obey the guidelines of the book Glow15. That means to reduce the number of proteins for two to three times a week (to about 20 g). Concomitantly with the reduction in protein intake, I don't eat anything after lunch until the next breakfast. After a total of 16 hours with no single calorie, I fill up my reserves on the next day again (important!). The goal is to give the body the opportunity to digest all the scrap so that at least a few days a week your cells can get cleaner. However, to prevent your body from getting its protein from the muscles or even the brain, it is necessary to fast only on one day but to ingest sufficient protein on the next day. Please keep in mind that if you continue to fast your body will eventually take what he needed. We had discussed this in more detail in the first section of the fifth article. Personally, I think the intermittent fasting is also relatively unproblematic concerning your health. But once more, if there are medical problems, ask a doctor first. However, a look at current articles on the topic shows that adverse effects are not necessarily known, but the benefits must be researched even more carefully [41].

                   3.   Sports

Sport is one of the most important but also one of the most overrated aspects. I've done a lot of different kinds of sports in my life (karate, soccer, bouldering, jogging, swimming, and even weight training) and I have to say that sports are really important for especially two things: Keeping your body agile and fit, and your mind clear. It also depends totally on the person which kind of sports can be performed on a sufficient level. For me, above all, I can't live without my NaturFitTraining. This training always takes place outdoors and always together with other people. The NaturFitTraining can be imagined as a healthy mix of bodyweight and endurance training. Anytime our trainers introduce funny new workouts and tasks. It keeps you fit, it's funny, you are doing sports together with other people and it's a challenge for you anytime because you decide how far you want to go. Marvelous! But the most important. I always have in mind that it has been shown several times that sport directly (!) Induces autophagy [42-44]. Of huge importance in this context is also the finding that studies have found that the intake of antioxidants (for instance of vitamins) after exercise is not a good idea. Intriguingly, a huge benefit of sports is the activation of stress pathways. Antioxidants, however, are blocking these beneficial pathways [45]. These pathways are primarily stress-responses induced by oxidative stress (the much-cited radicals & Co.). As a consequence of moderate oxidative stress for a short time you receive a boost in health [45, 46]. In addition, there are also very clear correlations of oxidative stress and autophagy as you can read in two brilliant review articles [47, 48]. Sport, therefore, causes a positive stress (if you want) with multiple advantages for various cellular reactions (Maybe I'll talk more about that in another article.)

But what do I mean when I say that sport is an overrated aspect? I just mean that the assumption that sports will cover any escapade is just a fallacy. Sports will never protect you from the negative effects of poor nutrition or even harmful food. No chance! Even though sports induce valuable pathways (including autophagy) it does not mean, that you can eat every trash. The success of exercise (e.g., weight loss) highly depends primarily on the diet [49]! Most of your energy is consumed by your brain, your kidneys, and your heart. Even though you may have gained some more muscle, this will not give you an astronomical increase in your basal metabolic rate [50]. And these finds holds also true in the case of autophagy. Just because you're doing some sports, you do not have a free ticket to eat every trash. The fight of Packman and "The ghosts" is just too hard. Decide which side you prefer.

                   4.   Intake of supplements

A very critical subject, I know. In principle, I have to say that I have a bad feeling concerning supplement intake. I also did some research, but I have to admit that the complexity in this field does not allow you to give a reasonably reliable answer. In his book "Der Ernährungskompass" the author Bas Kast concludes that taking vitamins is basically always a bad idea, except for vitamin B complex or vitamin D3 [6].

[At this point I have to apologize to all non-German speakers because the book of Bas Kast is solely available in German at the moment. In my opinion, this book contains really important information concerning food and health. And also in an excellent researched manner. I hope that this book will be translated into English as well one day to enable the entire mankind to benefit from it. Me, for my part, don’t know any book that could be compared to “Der Ernährungskompass”. So, check out if a release in English or other languages is coming up.]

In my opinion, the argumentation of Bas Kast is completely conclusive. Therefore, I’m thinking about vitamin D3 supplementation, maybe this winter.

Since all three substances are used in kitchen and medicine for thousands of years a basic benefit for your fitness will be associated with them in any case. Nowadays, their mechanisms have been studied in a more detailed fashion, and preparations have been available for quite some time, allowing you to use those substances in higher doses. However, if you do some literature research about them you will notice, among others, that the bioavailability after oral application of all three substances is very low (in some cases below 1%) [51-53]. This means that e.g. orally taken substances of this kind will pass through detoxification mechanisms or other processes and are eventually modified or even completely degraded. Therefore you have to ask whether 1) the intake has any consequence for you and 2) whether the results that were collected, for example, in a laboratory are in accordance with the function in your body. In the article by Cyprianj you can find more information concerning this subject . Fortunately, these days a plenty of methods are known to improve the bioavailability, for example by chemical modification [53] or by the addition of other substances such as pepper. This procedure, for instance, elevates the bioavailability of curcumin by incredible 2000% [54]. In particular, trans-resveratrol and curcumin, have many positive aspects I should mention. At first, Basically, there are no serious side effects after intake known (except in the case of very high doses), which is the first very good argument for the supplementation [52-54]. Take a look at all of the quoted articles thoroughly yourself before using curcumin, trans-resveratrol (that's the active form !!!) or berberine. In my opinion, the intake of up to 500 mg per day is almost harmless. But here again applies: Asking a doctor never hurts! But which benefit does these three substances have in the connection to autophagy? Please take a closer look at the following picture:

In accordance with various laboratory results, all three supplements promote autophagy [55-59]. The activation of Packman seems to be primarily due to the fact that the key suppressors (AKT, ERK and especially mTOR) are the targets of curcumin, trans-resveratrol and berberine. This can be done by a more or less direct inhibition, as with curcumin or trans-resveratrol [56, 60-62] or indirectly through the activation of AMPK as in the case of berberine [55]. But it is also possible that these substances even trigger the activation of ERK, which has already been shown [63]. And even berberine has already been observed while inhibiting autophagy (by the way, in cells of adipose tissue) [64]. Honestly, in the end, I can not judge what trans-resveratrol, curcumin, and berberine actually do in your body. Given the current state of scientific literature, I tend to assume that the three actually cause autophagy. The truth may be much more complex and in turn, is affected by numerous factors. It always depends on what else is going on in the cell. Indeed, it was shown in many studies that a substance that should in principle inhibit something, sometimes has opposing effects. Just look at the paper of Wu et al. for example [65]. Even if you are not in the mood to check just one article I have quoted here, please check at least the article of Wu et al. The authors show that the common autophagy inhibitor 3-MA even activates autophagy, depending on the condition of the cells (duration of action, little or much to eat ...). These results suggest that you can never be sure (especially not in the case of autophagy where "thousands" of parameters affect each other) which is really "true". Thanks again to Wu et al. for the marvelous work. Nevertheless, I think that potential effects of curcumin and trans (!) - resveratrol has been figured out very well (even clinically) so far. To summarize it, yes substances like this might be healthy, at least they are not harmful. So, above all, always consume plenty of Indian food (curcumin) and drink plenty of wine (resveratrol). Enjoy your meal!

Summary

I think it's time to summarize the findings in a more condensed form. Take a look at the next table, please.

I think there are not that many questions left! You may also have noticed that you can not drastically reduce the protein content in your diet, as this will (as described above) cause your body to actively search for protein, which is reflected in uncontrolled eating attacks. The result: Higher calorie intake, thus more insulin, as well as a lower AMP: ATP ratio. Accordingly, mTOR is again increasingly activated, etc., etc., etc. I really recommend you use vegetable sources of protein, it satisfies the hunger and keeps mTOR at a moderate level.

Additional information

One thing I should perhaps still address in the end, namely green tea and sleep. I deliberately did not list these both components above for two reasons.

First of all, it should be clear to everyone that you have to sleep well, although science is still not quite sure how much. The fact is that if you have slept well, then everything is ok. If you feel tired all the time, then you should act. With regard to mTOR and autophagy, there are also different results on the subject. On the one hand, mTOR is inhibited by lack of sleep, resulting in limited ability to memorize [66]. On the other hand, it has also been shown that autophagy correlates very closely with your sleep-wake rhythm [67]. Remember that your entire metabolism depends on the sleep-wake rhythm (think, for instance, of melatonin, which regulates insulin secretion [15, 16]). Remember that your entire metabolism depends on the sleep-wake rhythm (think, for instance, of melatonin, which regulates insulin secretion. Therefore, it's easy to understand why even autophagy must be dependent on the sleep-wake rhythm. I do not add this issue to the list because any person with common sense should know that sleep is an important part of life and the optimal adjustment of your sleep-wake rhythm should be on the top of your priority list.

Second, I think green tea is an absolutely great drink. I drink between 6 and 10 cups every day, sometimes more. I love green tea and consume him in enormous quantities for years. I like its taste, I like how green tea looks like, I like the way to prepare him, I like all the different varieties and I'm always happy when I get one I do not know yet. One of our Chinese exchange students even has sent green tea to me from China, allowing me to compare green tea directly from China with Chinese green tea directly from the German health food store. Maybe this tea heals me and explains why I never get sick, maybe it has no effect. The literature on the subject is certainly very controversial and I can't, therefore, make no scientific-proven recommendation to you. [68]. But the fact is that green tea will not kill you. Enjoy!

Also important

I should also continue to draw attention to one thing, it's about the trend I created in this series of articles. Maybe you have not noticed it yet, but I have more or less deliberately tried to frame the cellular packman (the autophagy) is an angel and mTOR together with his friends as some kind of satanic conspiracy within your body. But you can also change the roles and will be, despite this, right under some conditions.

It is important to understand that death is part of life and has an eminent role in maintaining your health. Dying processes kill off billions of cells (up to10 billion) in your body every day. It's important to remove cell which is too old, damaged or simply degenerated to keep your body healthy and fresh It is, of course, crucial that these mechanisms are excellently regulated, which is primarily due to regulated cell death, apoptosis [70]. Moreover, after cell death, fresh cells must be created to fill the gaps and for this task Packman's enemies "The Ghosts" (mTOR, AKT, ERK and many others) are responsible [71]. Therefore, nothing works without "The Ghosts"! Furthermore, in addition to apoptosis, there are also other cell death events such as necrosis (more on this perhaps elsewhere) [72]. For some years, yet another cell death mechanism has been observed, namely the so-called autophagy-mediated cell death or simply autosis [73]. This cell death mechanism cannot be prevented by inhibitors of apoptosis and are promoted by an increased number of autophagy-related gene products. Although the data are more or less very preliminary, it appears that autophagy-induced cell death occurs mainly as a result of ischemia. Ischemias is described as an undersupply of tissues with blood or oxygen (as in strokes, for example), which can lead to severe cell death events [46]. But its not restricted to stroke or heart attack. Even in the case of organ transplants, ischemias occur [74]. It has been shown in various studies that autophagy can make promote the death of cells under these conditions [75]. By inhibiting autophagy, it was observed that the damage can be reduced. But no worries, if you do not have a stroke or heart attack, or you neither need an organ transplant or are not suffering from ALS, then these findings should not affect you any further. By inhibiting autophagy, it was observed that the damage can be reduced. But no worries, if you do not have a stroke or heart attack, or you neither need an organ transplant or are not suffering from ALS, then these findings should not affect you any further. With this little excursion, I just want to make you, once more, aware you that you have to consider both sides of the coin sensibly and carefully (as with anything in life). But to briefly summarize this: To take care on your cellular Packman is definitely a good idea even when in some situation it might be a disadvantage. But to be honest, in these situations, you probably have much more problems than optimizing your Packman.

Conclusion

Autophagy is a wonderful tool to cleanse your cells and to keep your health at its best. However, different circumstances in life are preventing autophagy. Examples of these bad influences are: too much food and/or food of poor quality, bad timing of food intake, no or inadequate exercise, negative stress, poor sleep and much more. Intermittent fasting, regular exercise, as well as the intake of some supplements such as trans-resveratrol, curcumin, etc. are able to promote autophagy. In particular, however, by the moderate consumption or by the partial waiver of animal products (such as meat or milk), a positive contribution to autophagy and other health-promoting mechanisms can be achieved. Especially, the intake of natural products is highly recommended. But even smaller habits like drinking coffee have a positive effect on autophagy, as coffee inhibits mTOR (should be avoided during pregnancy!) [6, 76]. However, it is always important to find a healthy balance. For instance, do not overdo it with fasting (never several in a row) and take plenty of protein to prevent a yo-yo effect after fasting (but best vegetable!). Negative effects of autophagy are likely to be limited to very harsh health conditions and not relevant to the majority of people. Some of these situations can even be prevented by an "autophagy-lasting" lifestyle.

I wish you all the best by finding your way.

Have a nice week

Your Chapper

Epilogue

If you liked the article, leave me a comment. But even if you are not agree with some things: Just say it! I think it is very important to give people as much and especially well-researched information as possible. But please always remain polite and prove your view with some references. Many Thanks.

References

I did all the figures by myself. Therefore, feel free to use them. But please note that the sugar pieces in the figure with the metabolism are from Pixabay. The protein molecular structures of mTOR, ERK und AKT I found the Protein Data Bank. The molecule structures in the figures of NAD, NADP und ATP are from Wikipedia.

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Have fun