Affect of Prolonged Fasting on Hematopoietic Stem Cells

My writing should serve you no other purpose than a brief knowledge about the article. I have summarized the whole article, didn’t go into details, and didn’t mention nearly all of the experiments they have done. I have only written the results that are the most important. If you want to learn more about this subject, you should read this article. I can guarantee you that this article is a very good and interesting article.

Another thing is I didn’t give any references, because I didn’t use any articles other than this one. When I am going to give summary of new articles, I will gather more information about the subject of the article.

INTRODUCTION

Prolonged fasting (PF) lasting 48–120 hr reduces progrowth signaling and activates pathways that enhance cellular resistance to toxins in mice and humans. Only after more than 24 hours of fasting, the stored glycogen in the body is depleted and the body fully switches to a fat- and ketone bodies catabolism.

Previous studies in mice have shown that PF can reduce the circulating insulin-like growth factor-1 (IGF-1), which protects cells against chemotoxicity. There are also some studies, which show that PF can cure several side effects of chemotherapy. Part of this study focuses on myelosuppression, which is reduction in production of blood cells. This side effect often cause dose limiting in chemotherapy treatment.

Hematopoietic stem and progenitor cells (HSPCs) include long-term (LT-HSC) and short-term hematopoietic stem cells (ST-HSC) and the multipotent progenitors (MPP). These cells reside in the adult bone marrow (BM) and responsible for hematopoietic regeneration.

RESULTS

Chemotherapy drugs cause DNA damage and cell death of cancer cells. However, this process is not limited to cancer cells. Along with them, chemotherapy drugs also affect somatic cells, which include LT-HSC, ST-HSC, and MPP cells. This treatment, eventually causes impairment of hematopoiesis.

In the experiments, they have used multiple cycles of cyclophosphamide (CP), which is a chemotherapy drug, on fasted or fed mice. 48 hr PF decreased the DNA damage caused by CP and had an effect of protection in leukocytes and BM cells. Then they have checked whether CP causes apoptosis in PF treated cells and shown that PF actually protects HSPCs against CP-induced apoptosis, especially for two subtypes of HSPCs.

They have also shown that PF doesn’t protect HSPCs against chemotherapy at first, however it improves hematopoietic recovery in later cycles. After 4th cycle of CP treatment (39th day), the beneficial effect of PF was observed by the scientists. After 5th cycle of CP treatment (56th day), lymphocyte levels returned to the normal levels. At the end of 6th cycle of CP treatment (70th day), lymphoid cell levels and ratio of lymphoid and myeloid cells (L/M) returned to normal levels.

In humans, they have tried PF for cancer patients from a phase I clinical trial. For 72 hr of PF, the lymphocyte counts were returned back to normal. Now, they need to make the same experiments with patients from phase II clinical trial.

Furthermore, they have taken CP-treated and PF + CP-treated mice BM cells and transplanted them to mice with impaired immune system. As a result, they have observed that PF + CP-treated mice BM cells had higher regeneration capacity.

Then, they wanted to find if PF can induce HSC self-renewal without chemotherapy. They have seen 6-fold increase in newly generated HSPCs compared to the control group. They have checked cell numbers of each subtype and found that LT-HSC and ST-HSC levels are increased and the number of total BM cells was not increased by PF.

Furthermore, number of common myeloid progenitor number was slightly decreased as a result of PF. Then, they have observed that PF induced a major increase of S/G2/M phase of LT-HSCs and ST-HSCs. Another interesting result was that PF reduced apoptosis significantly.

8 cycles of PF can also reverse age-dependent myeloid bias in HSC subtypes and reverse effect of aging on WBC number.

In a previous study, they have shown that PF reduces circulating IGF-1 levels, which protect mice against chemotherapy toxicity. In the low amounts of IGF-1, the cells are protected against apoptosis, too. They also have increased self-renewal of HSC, similar to PF. PKA catalytic subunit alpha expression level was reduced in all tissues of starved mice and humans. They have also confirmed a link between IGF-1 and PKA/CREB and PF can reduce PKA signaling via low IGF-1 levels.

CONCLUSION

Prolong fasting reduces circulating IGF-1 in blood, thus, downregulates PKA levels, which in turn promotes hematopoietic stem cell self-renewal. PF can also be used along with chemotherapy. It showed promising results in humans and recovered white blood cell levels to their normal levels after 6 cycle of PF and CP (chemotherapy drug) treatment.

 

 

Cheng, Chia-Wei, et al. “Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression.” Cell Stem Cell 18.2 (2016): 291-292.

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Affect of Prolonged Fasting on Hematopoietic Stem Cells

AN ESSAY ABOUT WHY YOU ARE NOT LEFT OR RIGHT BRAINED

Yesterday, I have talked with a friend about a subject. At one point, she told me four wrong statements she believes because a doctor told her. First one was “our right brain is creative and our left brain is analytical”. Second wrong statement was “our left brain controls all of our organs”. Third statement was “our right brain accepts every statement”. The final statement was “Since our left brain is analytical, it slows us down, which is bad”. I would like to write about why these statements are wrong and prove them scientifically.

 

First of all, dietitians and doctors rarely understand what science is about, similar to situation between chemical engineers and chemists; they do not try to discover a scientific fact, but try to apply the scientific fact. Therefore, for a doctor, it is important to cure a disease, no matter protein A or B cures the patient. However, for a scientist, it is important to know which one of these proteins actually cures the disease. To make the matter worse, media try to oversimplify the science and create false stories, intentionally. This topic is going to be theme of my next essay, but I would like to give you some examples.

 

Let’s begin with a simple example. Are trans fats bad for you? Everybody can answer this question with a full confident: Yes! Why are they bad for you? Okay, not everybody can answer this question but some people can tell you that “we cannot process trans fats in our bodies, so they accumulate”. Nobody can oppose these answers, because there is not evidence that opposes these facts. Now, are chicken eggs bad for you? The thing is some doctors say it decreases blood pressure, some doctors say it increases blood pressure and your cholesterol, and some doctors say that eggs do not change your cholesterol level. I think you got my point. There is no clear answer for egg. Why is that so? Because it is not scientifically proven! I can tell you the reason why the trans fats are bad for you, your body can’t process them and they accumulate. Can someone tell me why chicken eggs decrease or increase blood pressure or cholesterol level? With what mechanisms and signal pathways do chicken eggs induce cholesterol production? Can we not process cholesterol, similar to trans fats? There are no answers for these questions.

 

So where do these conclusions for chicken eggs, coffee, teas, and other foods come from? They come from the statistical results of experimental subjects that consume these foods. They look at what percentage of these experimental subjects that eat chicken eggs, have cholesterol level above the average. After finding out the result, they create an article and publish it. One of the problems with this approach is the sample size of the experimental subjects. If I invite three people to my house and two of the virtual people have blue eyes, do I conclude that majority of the people outside have blue eyes or two-thirds of people have blue eyes? Then, it is important to have high sample sizes for experiments, especially with something as complicated as cholesterol levels. Other problem is that no matter how hard you try to make a control group, the individuals always will have differences. So, a person’s cholesterol level might have increased that day because of the food the person ate. More examples can be given considering gender, age, diet, and other variables for people, but the point is that in order to conclude something with a scientific proof, you need to eliminate all other possibilities, which requires molecular level approach, instead of statistical analysis. Of course, statistical analysis is important, don’t get me wrong. The problem is the conclusion, which you shouldn’t make right after you read an article, so that we wouldn’t have an article on TIME that claims “Scientists say smelling farts might prevent cancer”. The TIME article is real, except they changed it later considering how stupid it is. That article in that serious magazine shows us how serious these problems are. Last but not the least, some of these statistical analyses is done with experimental subjects, which are not human. The fact that chicken eggs increase a rodent’s cholesterol levels doesn’t mean that they would increase your cholesterol levels, too. Yet, those articles are published –and they should be published– and media immediately come to the conclusion that you should never eat a chicken egg in your life.

 

LpOGvZ9
I told you I wasn’t joking

 

Now that I have talked about the scientific approach and mediatic approach to the science, I would like talk about the left and right brains. The asymmetry of brain was pointed out as early as 5th century BC by Hippocrates. He has observed that if one side of the brain is damaged, the opposite side of the body would have seizures [1]. Later years the observation became a fact. Furthermore, it is observed that epileptic seizures in one hemisphere often cross over and cause seizures in the other hemisphere [2]. In early 1960s, Roger Sperry, Joseph Bogen, and Philip Vogel speculated that cutting corpus callosum, which connects two hemispheres, might prevent crossing of the seizure. The patients’ symptoms were disappeared considerably. However, although they could be able to do their daily activities as normal, the patients, who held objects in their left hands out of sight, claimed they held nothing. They could feel and name the objects that are in their right hands. With further experiments they have concluded that our different brain hemispheres are specialized to do different things [2]. But, we now know that right brain hemisphere controls left hand and right hemisphere is limited –not incapable– of producing speech. Since, the corpus callosum was cut, the hemispheres can’t communicate with each other.

 

The communication of hemispheres is very important, because they require each other’s cooperation [3]. We produce speech with our left hemisphere, but we give our speech intonation with our right hemisphere [2]. So, we are able to say: “Of course that dress is red!” with our left brain hemisphere, but we say it as sarcasm not as a statement thanks to our right brain hemisphere. This phenomenon is so incredibly misunderstood; most people interpret as if we have two distinct brains, one of them is artistic and the other one is analytical. Neurologists even named this phenomenon as dichotomania.

 

Right Brain, Left Brain, Whole Brain8
That’s right! We have individual brains, just like our lungs. See? I used my right brain hemisphere.

 

There is no scientific paper or mediatic paper that talks about relationship between our left brain hemisphere and all of our organs. In fact, it is known that our left brain hemisphere controls our right side of body and our right brain hemisphere controls our left side of body. There is also no scientific paper, which is written about which of our hemisphere accepts every statements and which denies or be neutral about it.

 

For the final fact, assume that our left brain hemisphere is analytical and slows us down. Is it a bad thing? The thing is we actually accept every statement immediately, although left or right side of our brain has nothing to do with it. When I talk about yellow mice, most of the people imagine a yellow rat, before dismissing the fact that yellow rats don’t exist. This process of accepting every fact and then eliminating them is done in our daily lives and we generally do not notice it.

 

Analytical thinking –not that I claim it comes from left brain hemisphere– is what we must actually do. If we want to find a truth behind many lies and false information, we have to question every statement we see, including this essay. So, what do you think about these statements and my approach to these statements. Please don’t forget to comment below.

 


 

REFERENCES

  1. LeMay, M. “Left-right dissymmetry, handedness.” American Journal of Neuroradiology 13.2 (1992): 493-504.
  2. Wolfe, Patricia. Brain matters: Translating research into classroom practice. ASCD, (2010): 44-48.
  3. Brodal, Per. The central nervous system: structure and function. Oxford University Press, (2004): 593.
AN ESSAY ABOUT WHY YOU ARE NOT LEFT OR RIGHT BRAINED