How long after eating before authophagy starts?

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LanceS
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Re: How long after eating before authophagy starts?

Postby LanceS » Wed Nov 28, 2018 6:34 pm

Attia has a recent interview with Thomas Seyfried where the touch a little bit on fasting ... got the sense that Seyfried was saying the more you do it the more adapted your body becomes the less autophagy you'll experience

got the sense he would say it was more than 24 hours, but I think that was for people who fast alot... before I started fasting, I'd have said under a day, not sure any more fasting 16 hours is not a big deal at all... though I do think what you eat and how much you eat how much exercise you get start to matter alot in the equation

the context is pushing the cells into apoptosis which have mitochondrial damage / insufficiency... only half way through ... probably not worth the read to just hear them dance around the autophagy issue, but if you're into the other stuff, probably worth it... i dunno TS seems to be pushing into pretty cools ways to reduce sugar levels and purging cells that are in need of purging... didn't really seem like a safe deal for homegamers... like you needed medical assistance with the stuff (mostly to keep glycine in check, but he also goes after sugar levels aggressively)

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Re: How long after eating before authophagy starts?

Postby mike » Thu Nov 29, 2018 3:20 pm

Autophagy need not start when the liver removes its last glycogen if you have fat reserves - your fat can be broken down into glucose which can then supply either glycogen or energy needs not met by ketones. It is still good to give the live a break, even if you don't get autophagy. Pointing to mouse studies really doesn't count here, since our metabolisms are so different. In these studies, the mouse was losing 10% body weight - and that doesn't happen overnight, or even in five days, in humans. And the talk about muscle loss - I just finished a 19 day water fast 3 weeks ago. After rebuilding, I'm back to what I was pre-fast, in terms of what I could do on the volleyball court. I lost 10% (21 lbs) and have since put back about 6 lbs of that. I never had any heart issues, though I did not work out hard during the fast. The body doesn't just go out and randomly remove muscle cells. First off, it doesn't remove many actual cells, they just get smaller. And now they are back strength/endurance wise, yet I'm still 15 pounds down. I will work to build up muscle further until I'm back up another 4 or 5 pounds.
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Re: How long after eating before authophagy starts?

Postby thlas1971! » Thu Dec 27, 2018 10:30 am

So autography is when ratios are below 1:1? I can do that in about 20 hours of fasting. Yesterday I did a 24 hour fast and at the end I had glucose of 65 and ketones of 5.4 with a ratio of 0.7. Only once over the past month were my ketones below 3.0 with an average ratio of about 1.3. Should I be grateful for this as I can easily enter autophagy or is something wrong with me that I can get there so quickly? I follow a ketogenic diet with no exogenous ketone supplements.
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Re: How long after eating before authophagy starts?

Postby floramaria » Thu Dec 27, 2018 8:12 pm

thlas1971! wrote:So autography is when ratios are below 1:1? I can do that in about 20 hours of fasting. Yesterday I did a 24 hour fast and at the end I had glucose of 65 and ketones of 5.4 with a ratio of 0.7. Only once over the past month were my ketones below 3.0 with an average ratio of about 1.3. Should I be grateful for this as I can easily enter autophagy or is something wrong with me that I can get there so quickly? I follow a ketogenic diet with no exogenous ketone supplements.



I'm impressed! I have to fast for 36 hours to get to ketone level of 1.2. From my envious perspective , it definitely seems like something to be grateful for. :lol:
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Re: How long after eating before authophagy starts?

Postby Brian4 » Thu Jan 10, 2019 7:40 am

We know very little about autophagy in humans.

I think significant autophagy will likely take at least two days to kick in in humans, and that's only in certain tissues. It may take even longer to kick in in the brain, since the brain is energy-privileged.

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Re: How long after eating before authophagy starts?

Postby Julie G » Thu Jan 10, 2019 10:21 am

I wonder if autophagy can be viewed from a continuum or is it an "off/on"?

I read an interesting preview to a tutorial comparing autophagy to apoptosis. They use a clever dinner vs. death analogy to explain the concept. ;) We have lots of suggestions that E4 predispose us to early apoptosis through mitochondrial deficits, etc, leading me to strongly suspect that autophagy is even more important for us...

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Re: How long after eating before authophagy starts?

Postby Brian4 » Fri Jan 11, 2019 6:46 am

Important question Julie.

I'm pretty sure it's mostly on/off. In other words, it's definitely not linear: 10% autophagy at 10% of the way towards the 2.5-day mark (for tissues where 2.5 days is the relevant figure...), 30% at 30% of the way... etc. But it doesn't suddenly go from zero to full-on autophagy at a certain point.

But, apparently, the relevant genes just don't get turned on, much anyway – in humans – until at least a couple days of fasting (or near-fasting) have gone by. But no one is quite certain yet.

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Re: How long after eating before authophagy starts?

Postby mike » Fri Jan 11, 2019 10:52 am

I was unable to read past the beginning of the tutorial Julie, without being a member. In the article below they talk about autophagy and apoptosis as a more ongoing thing. Cell death is needed in multi-cellular animals, and how the death occurs, is important. Autophagy being a method to possibly preserve the cell, or to more orderly dispose of the parts if death is needed. During fasting, cells can clean house using autophagy without dying - muscle mass drops, but number of cells doesn't drop that much.

https://www.nature.com/articles/s41392-018-0018-5

I just found this article as well, and it seems easier to understand: https://www.cusabio.com/c-20683.html

In the cellular energy crisis, autophagy also provides energy and nutrients to cells through the digestion of large molecules such as organelles and proteins, prolonging cell life. Thus, autophagy is required for cell survival in the starvation phase of adult mice, the feeding adaptation period after sucking rats, and the nutrient-deprived cells [8].


I wonder if a person with fat reserves would see much autophagy during fasting, since there would not be the same energy crisis...

And here is another easy to read article by Dr Fung that uses a car as example - get new car (apoptosis) or fix the car (autophagy). This also discusses fasting and how autophagy can help with AD: https://idmprogram.com/fasting-and-autophagy-fasting-25/

Nutrient deprivation is the key activator of autophagy. Remember that glucagon is kind of the opposite hormone to insulin. It’s like the game we played as kids – ‘opposite day’. If insulin goes up, glucagon goes down. If insulin goes down, glucagon goes up. As we eat insulin goes up and glucagon goes down. When we don’t eat (fast) insulin goes down and glucagon goes up. This increase in glucagon stimulates the process of autophagy. In fact, fasting (raises glucagon) provides the greatest known boost to autophagy.

This is in essence a form of cellular cleansing. The body identifies old and substandard cellular equipment and marks it for destruction. It is the accumulation of all this junk that may be responsible for many of the effects of aging.

Fasting is actually far more beneficial than just stimulating autophagy. It does two good things. By stimulating autophagy, we are clearing out all our old, junky proteins and cellular parts. At the same time, fasting also stimulates growth hormone, which tells our body to start producing some new snazzy parts for the body. We are really giving our bodies the complete renovation.


What turns off autophagy? Eating. Glucose, insulin (or decreased glucagon) and proteins all turn off this self-cleaning process. And it doesn’t take much. Even a small amount of amino acid (leucine) could stop autophagy cold. So this process of autophagy is unique to fasting – something not found in simple caloric restriction or dieting.
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Re: How long after eating before authophagy starts?

Postby Julie G » Sat Jan 12, 2019 1:36 pm

It's mice... but still hopeful ;)

Short-term fasting induces profound neuronal autophagy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106288/
Abstract
Disruption of autophagy—a key homeostatic process in which cytosolic components are degraded and recycled through lysosomes—can cause neurodegeneration in tissue culture and in vivo. Upregulation of this pathway may be neuroprotective, and much effort is being invested in developing drugs that cross the blood brain barrier and increase neuronal autophagy. One well-recognized way of inducing autophagy is by food restriction, which upregulates autophagy in many organs including the liver; but current dogma holds that the brain escapes this effect, perhaps because it is a metabolically privileged site. Here, we have re-evaluated this tenet using a novel approach that allows us to detect, enumerate and characterize autophagosomes in vivo. We first validate the approach by showing that it allows the identification and characterization of autophagosomes in the livers of food-restricted mice. We use the method to identify constitutive autophagosomes in cortical neurons and Purkinje cells, and we show that short-term fasting leads to a dramatic upregulation in neuronal autophagy. The increased neuronal autophagy is revealed by changes in autophagosome abundance and characteristics, and by diminished neuronal mTOR activity in vivo, demonstrated by a reduction in levels of phosphorylated S6 ribosomal protein in Purkinje cells. The increased abundance of autophagosomes in Purkinje cells was confirmed using transmission electron microscopy. Our data lead us to speculate that sporadic fasting might represent a simple, safe and inexpensive means to promote this potentially therapeutic neuronal response.

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Re: How long after eating before authophagy starts?

Postby Jpmb.ic@gmx.com » Tue Jan 15, 2019 6:41 am

Great question. I tired to find the same answer. But could not find anything definitive. Hopefully, one day there is a test.
In the meantime I have come to the conclusion to have reasonable confidence I get into autophagy it must be a fast over 48 hours.
It would be logical to assume it would also depend on how healthy/metabolic healthy you are.
So I aim for 4 days, 96 hours. On a relatively strict water fast (only additional electrolytes).

John


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