Interesting discussion. My doctor and I have been listening to several of Peter Attia's The Drive interviews and discussions on these topics. Of course, a lot of the folks discussing these topics are healthy, male, longevity biohackers, so one must translate for our set of problems, and be wary of the pitfalls.
We've been trying to figure out ways to improve my immune function, kill off senescent cells, and improve general performance, do have been experimenting in this area. I think the research is fantastic, but don't have time to wait for them to finish it - trying to benefit now by guessing and experimenting....
One study I read showed that Rapamycin blocks the phosphorylation of ATG13 but it didn’t help me.
Rapamycin doesn’t seem to be effective unfortunately.
I discussed a Rapamycin trial with Ron Davis years ago. There was some interest in mTOR from them but then it didn’t seem to help a few of us and it faded away.
I've been on low dose rapamycin (Sirolimus) for the past year. At regular doses, it is an immunosuppressant, used in organ transplant patients. At low doses, it is theoretically an immunostimulant. I did not find that it really helped, and in the end, a low dose taken twice weekly seemed to be suppressing my immune system, as my HSV2 was always on the verge of an outbreak, even though I also take a significant amount of Valcyte. Going off of it has improved the situation and I'm now able to back off the Valcyte.
I had been building up to a basic fast with five weeks of 8hr on / 16 hr off and so I tried a 36 hour fast last weekend. I was at the mildest end of moderate or better and wondering if I could accelerate things from there. Felt excellent with the fast and would have been happy to continue but didn't want to push it first go, as I knew that symptoms might increase. Confirmed I was in ketogenesis, with a finger-prick stab. Figures were much higher than my wife who has been shadowing me through this.
Broke the fast with a reasonable, moderate brunch - again low, almost zero carb. Felt great for the rest of the day until early evening, when things started to deteriorate: POTS and fatigue dominating which have been slowly settling over the week.
Difficult to know what to make of this. Expected as above? Metabolic derangement incapable of sustaining a fast? Incorrect break-fast? Effect of other supplements/drugs (I stopped everything but a single prescription med that I thought inadvisable to cease). Should I have waited longer before restarting? Lingering effect of flu shot the weekend before?
ME/CFS patients tend to be short of amino acids, certain lipids, B vitamins, minerals, and antioxidants. It is highly risky to restrict nutrition in the situation. I have read all about the benefits of intermittent fasting, water fasting, etc. But I really think the risks equal the benefits.
I also followed up on Valtrex Longo's Prolon fasting mimicking diet, speaking at length to their intake doctor, sharing my labs, my health history, as well as that I'm celiac and allergic to corn and quinoa. He quickly decided that the diet was not at all suitable for me and could cause me harm. He also shared that, contrary to the hype, no B cell autoimmunity had been reversed on such a diet.
. Autophagy should recycle immune cells for new ones - it would be great if the new ones were better behaved.
That's true!
If you want to experiment, coffee, green tea, curcumin, ginger, Ceylon cinnamon, ginseng, garlic, chaga and reishi mushrooms,, pomegranate, elderberries, bergamot, berberine, resveratrol and MCT oil can all promote autophagy. So can exercise, which can be done carefully, with replenishment of amino acids, antioxidants, NAD+ precursors, etc.
@Pyrrhus I am also interested in how we can reduce oxidative stress in microglia. Melatonin, quercetin, curcumin and resveratrol are mitochondrial antioxidants and LDN reduces microglial inflammation. All are a part of my ongoing protocol and I believe they help.
Most of all, I wish someone would be looking at the big picture and testing treatment protocols that work on real patients. I'm all for figuring out exact mechanisms that are improving or harming various functions, but I think we are at the mercy of the quest for individual drugs that attack mechanism X or Y or Z separately.
We are a complex system of integrated systems, each with many individual moving parts, colored by out individual genetics and influenced by infections, toxicity, stress, and comorbid conditions. It would be lovely for someone to model this complex picture and then run it in realtime to see where the bottlenecks and overflows are, what's blocked, workarounds, etc.
Want a little bit more cud to chew? Two other concepts that have been raised with regard to the observed beneficial effects of intermittent fasting are ketogenesis and the idea that digestion is a form of exertion.
