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How fasting and exercise can supercharge the body's cellular vacuum cleaner

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Old 03-01-2019, 10:27 AM   #1
soccertese
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Default How fasting and exercise can supercharge the body's cellular vacuum cleaner

One of the many useful things our bodies do on their own is rid themselves of proteins that are no longer of use. Whether the proteins are defective, toxic or simply surplus to requirements, our cellular machinery can act swiftly and decisively when shedding this dead weight. But by figuring out new ways to control this process, scientists hope to uncover new treatments for a host of degenerative diseases such as Alzheimer's and Parkinson's, and they've just discovered some new levers in the form of fluctuating hormone levels triggered by exercise and fasting.

The body's natural protein-disposal mechanisms are necessary for the overall health of the organisms and the best understood of them is known as the ubiquitin-proteasome pathway. It works by tagging defective proteins with an ubiquitin molecule, with the protein-disposal unit then taking this "kiss of death" as a green light to embark on its destruction.

But sometimes the protein-disposal unit doesn't work properly, creating a backlog of misfolded proteins that are left to clog up the cell and impact the way it functions. So much so that scientists, including those at Harvard Medical School behind the new study, believe they act as precursors for neurodegenerative conditions such as Alzheimer's.

"We know that misfolded proteins accumulate in neurons in some neurodegenerative diseases, such as Alzheimer's, ALS, Parkinson's, and that this accumulation is associated with defects in protein destruction by the ubiquitin proteasome system," study lead author Jordan VerPlank explains to New Atlas. "In collaborative studies, we found in brains of a mouse models of Alzheimer's disease and early-onset dementia that the expression of the mutant tau reduced protein destruction by the proteasome and caused a further accumulation of misfolded proteins."

Thankfully, there are ways to swing things back in the protein-disposal unit's favor when it fails to do the job on its own. Previous research conducted by VerPlank and his fellow cell biologists has uncovered drugs that target a chemical trigger for protein destruction called cAMP and give the process a boost. But in doing so, the team began to wonder if they were overlooking a key, and potentially useful step, in the process.

"Because many hormones cause an intracellular rise in cAMP, we wondered if hormones would also stimulate protein degradation, or if the effect documented in the previous study was exclusive to the drugs used to raise cAMP," VerPlank tells us. "It turns out hormones do, in addition to their already known actions, indeed trigger protein destruction."

The scientists landed at this conclusion after a carefully designed round of experiments put their hypothesis to the test. They focused on the hormonal changes brought about through exercise and fasting and set out to observe changes in cells before and after.

"This is truly a new way of looking at whether we can turn up the cellular vacuum cleaner," says Alfred Goldberg, senior author on the study.

One experiment involved the thigh muscles of four human volunteers put through a tough cycling exercise, with the cAMP levels and signs of protein degradation heightened thereafter. Another involving the hind leg muscles of anesthetized rats brought similar results. As did tests on mouse liver cells exposed to a fasting-related hormone called glucago, as well as the hormone behind adrenaline, epinephrine.

"Thus, stimulating protein degradation by raising cAMP is not just a phenomenon seen with drugs, it also happens with many hormones and therefore is likely happening in our bodies all the time," says VerPlank.

With a new way to promote junk protein destruction, the scientists may have a new way to intervene in the development of diseases such as Alzheimer's, Parkinson's and ALS. Harnessing existing drugs or developing new ones that trigger this process as early forms of treatment will be subject to to further study. But if nothing else, the scientists have discovered yet another health benefit of regular exercise and added further weight to the argument that fasting can lead to a longer and healthier life.

Their research was published in the journal Proceedings of the National Academy of Sciences.

Source: Harvard University
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Old 03-01-2019, 07:01 PM   #2
jeffreyn
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More info from HMS, including link to research paper:

Vigorous exercise, fasting, hormones improve elimination of toxic, misfolded, unnecessary proteins in mouse and human cells -- ScienceDaily
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Old 09-17-2019, 07:37 PM   #3
momcaregiver
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Default Fasting for stem cell rebuilding

Doing short fasting cycles and plant strong diet in hopes of improvement for an anoxic brain injury in my adult son which produced parkinsonism symptoms and memory loss. Anyone else fasting for health as the proof is mounting in its favor on many fronts? I'm also doing it for rebuilding years of dietary abuse and my own bump to my head last year.
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Old 10-17-2019, 10:07 PM   #4
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Several years ago I saw the movie "First Do No Harm". It's based on a true story about a boy with epilepsy who wasn't helped by any of approved treatments. This was pre-internet so the Mom researched in a Library and found out about a Doctor who was having success with a special diet. Their Doctors said it wasn't proven and would not support it. The Mom managed to get her son to John's Hopkins learned the diet and the boy was helped. What really stood out for me was the some bit parts in the movie were played by real people with epilepsy (not actors) who were personally helped by the diet. This was the first time I'd heard of a keto diet -- before it got popular. The Doctor who developed it knew that fasting was good for the brain but wasn't sustainable so he realized that by having a high fat diet you can achieve the same effect on the brain.

Fast Forward several years to when I was suspecting I had PD. Someone suggested Dr. Terry Wahls diet since Dr Wahls had helped her own MS with it. The person who recommended it had been doing it for several years. He was motivated to do it because he's an ultra marathoner. By going keto and burning fat he could run 10 hours straight and not have to refuel since even though he's quite thin, he has some fat.

The Wahls diet is basically keto with good fats (coconut and olive oil) and a lot of vegetables. (Apparently the coconut lets you eat more vegetables and still stay in ketosis.) So by following this diet I think I'm getting the effect of fasting. I've been doing it a little more than 6 months and it has gotten easier. I think Wendy is the only one on NeuroTalk who mentioned the Wahls diet, but it didn't sound like she stuck with it. There is a TEDTalk that you can see with Dr. Wahls about "Minding Your Mitochondria".
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