#21

Interesting. He said his 5 days referred to the time it takes to be measurable by some methods in some blood cells, but stated that of course it can be different in other tissues.

One thing I wonder about regarding these methods to measure autophagy. Maybe the stimulation takes several day sto show up as changes in these markers, even if it’s activated much earlier than that. As an example, if one would fast for only one day but measure autophagy markers in the blood 5 days later, would they be clearly elevated then, even though they were not in the first few days? Also maybe the tests aren’t sensitive enough to clearly detect the more modest increase in autophagy after shorter fasts.

Btw the reasoning for my strong skepticism of any claims that autophagy isn’t strongly activated until after more than 24 hours of fasting is based on the fact that, when you fast and your liver glycogen starts getting depleted, you must produce glucose from your own proteins to survive, by breaking down your tissues. Much of this breakdown basically is autophagy so it would be very strange for it to not increase fairly quickly after starting a fast.

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#22

Maybe we have the breakdown of glycogen in the muscles, then the breakdown of protein.
But, according to the following definition, you would be right, that is, breakdown of muscle protein during starvation can be defined autophagy according to the authors.

Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles - PMC.

Autophagy can be defined as a process of cytosolic ‘renovation,’ crucial in cell fate decisions.1,2 The autophagic/lysosome system is involved in the degradation of organelles and long-lived proteins and in the clearance of damaged cell components. Furthermore, the autophagic machinery is able to degrade part of the cell material in order to fulfill energetic needs during starvation and stress.

So, if there is glycogen breakdown first, then when a proper degradation of muscle cells occurs?

Probably sooner than 5 days, but as you hypothesize, this does not become soon detectable by the essays presently available.

#23

Yes, but the problem is that the glycogen in the muscles can only be used by the muscles themselves. It cannot be released into the blood to be used by other tissues. So the brain can’t use it and the brain needs glucose to survive. The brain can use the glucose stored in the liver when the liver breaks down glycogen and secretes it as glucose into the blood.

Yes, the brain can use glucose from the liver. When you start fasting, your body will use up the liver glycogen slowly, but the liver only contains around 50-75g of glucose and it takes roughly 12-24 hours for that to get pretty much empty, so during that time the body will have to start beaking down more and more proteins to create glucose for the brain to use. That’s why I think autophagy activation will be pretty strong when you get closer to the 24 hour mark

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#24

Here I confess ignorance. In the case of the beginning of a keto diet, it is said that many pounds are lost pretty soon due to the elimination of the glycogen from muscles and the water it binds. Is this a real phenomenon or just a wrong narrative? Of course, the loss of muscle tissue (autophagy) would cause loss of glycogen and the bound water.

#25

Yes that’s a real phenomenon. IIRC every one gram of glycogen holds something aroudn three grams of water so you lose quite a bit of water with the glycogen.

#26

Purely anecdotally. A couple of times a week (Mondays and Thursdays), I eat just one light meal (~500 calories) a day, in the early afternoon. These two days are my most intense exercise days, 32 minutes squats including jumping squats late morning, light meal afternoon, 50 minute jogging after meal, 30 minutes isometric. By the evening, and for many hours into the late evening up to midnight, I eat and drink nothing, but keep urinating seemingly huge amounts. I even have to go to the bathroom a couple of times at night. I always figured it was the water being freed from the system due to glucose disposal, and early autophagy. I have also read that in bodies that are habituated to generally low calories with regular longer periods of not eating (I practice TRF of about 18-20 hours of no food daily), the process of autophagy starts much earlier than for bodies that dont’t practice lower calorie, time restricted feeding. So while normally autophagy might kick in at 12-24 hours, in habituated bodies, the process might start at 6 hours. This was explored back in the day on the crsociety list. Here’s an example:

#27

I don’t want to be argumentative, but I honestly don’t understand a risk analysis where it makes sense to delay rapa after age 50 or 60. I’ve heard this reasoning from others (including Sabatini) and I don’t get it.

Here is what we know with reasonable certainty:

  1. You are aging now and will eventually develop an age related disease that will kill you.
  2. Your healthy lifestyle mitigates this risk, but rapamycin will likely further mitigate it. Although rapamycin MAY be redundant with your lifestyle interventions, it may also be additive. The idea that it’s redundant seems to be speculation only.
  3. Rapamycin dosed according to a typical longevity protocol is pretty safe. Worries about its impact on the immune system aren’t really justified, in fact human studies have shown a beneficial impact on immune function.
  4. Side effects are generally reversible, so if it’s not working for you, you can just stop.
  5. Studies in pretty much all model systems have shown longevity benefits.This includes human studies which have shown its benefits to the immune system.
  6. It’s unlikely that we’ll get results from an RCT that is sufficiently powered in the next few years to tell us if rapamycin impacts age-related diseases. Current studies are only powered to show safety, which has already been established when the drug was FDA approved.

Because of the above, for me it’s a no brainer to take rapa. Plus I have experienced some direct benefits. And although these may be placebo, they might also be caused by rapa.

Again it’s not my intention to be argumentative, but I thought I’d put this views forward in the spirit of intellectual curiosity and open inquiry.

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#28

@ageless64 I completely agree with your logic. It’s like you read my mind. :slight_smile:

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