The mTOR rebound effect has been kind to my skin?

I was dosing weekly at 4-5mg + GFJ + sometimes EVOO from February to July then in August I went to Europe and decided to take a break from all my supplements including rapa. I ate like there was no tomorrow there but ate excellently—a true Mediterranean diet in a Mediterranean country that in my experience has some of the best food, certainly best produce in the world. Two interesting things:

  1. my weight didn’t change, if anything now I’m about 5 lb lighter. My husband who went even crazier on the food there and normally gains 10lb when we go (every summer) didn’t gain a single pound. He’s also been on rapa this year but on smaller doses than me and more intermittently.

  2. my skin perked up extra by the end of the month there. I’d been working on my skin mostly by giving my face and neck a microneedling with radiofrequency treatment every 4-5 weeks (five so far in total). It was clearly working overall but my eye area was still not showing much improvement. At the end of the month of feasting it somehow remodeled itself. See pictures of before and after, where before is not right prior to the vacation but rather when I realized my health was going to :poop: in July 2022 and decided to embark on this “great intervention” of bio hacking. So it was already looking better by July 2023 but not THIS much better.

Also my neck had been slow to respond to the treatment but it somehow made up for lost time while I was on vacation.

Any theories as to why? The most disturbing hypothesis is that I should ditch all my supplements forever and just move to the old country but that can’t be right. I wonder if the feasting after months of starvation mimetic supplements (rapa + metformin + acarbose) had something to do with it. A desirable mTOR rebound effect?




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Great results!
Radofrequency results are starting to be more apparent at 6 months plus. Skin takes time. Maybe it is just that plus maybe eating more calories gave you just enough calories to replenish some of the subcutaneous fat?
And maybe just being on vacation made a difference. Less stress, taking it slower…

Ps. What supplements do you take?

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Maybe the cycling of supplements and pharmaceuticals is a good idea. In most things, a cycle is important. The question is what is the cycle period. Every 7 days seems a bit artificial to apply to everything. Whatever you are doing, keep going.

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I was trying to find the publication by Longo but it is the refeeding phase that the stemcells start regenerating not during the fasting phase

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Insulin-like growth factor-1, or IGF-1, plays a primary role in the refeeding phase that occurs after fasting, which is essential for the generation of healthy cells. During fasting, when IGF-1 is low, damaged cells die and stem cells are activated. However, during refeeding, IGF-1 levels rise and stem cells proliferate and continue to grow. Eating sufficient protein during refeeding is necessary to provide the essential amino acids for cell growth and also to stimulate the growth factor IGF-1, which provides the signals to rebuild.

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Yes that sounds about right. And it’s what I was thinking of. But then again before going on vacation I wasn’t exactly starving in America lol. I was still eating pretty well, avocado toasts, mushroom and hempseed omelets, a lot of olive oil, vegetable soups, wild salmon and vegetables were becoming staples at home. I also took a powdered collagen supplement. So no real fasting was happening, only maybe rapamycin in a high dose for a 5’3” woman was perhaps mimicking fasting. As healthy as this diet sounds on the books though it’s nothing compared to how I ate in the old country. I couldn’t even afford to eat that well regularly in the states. Or maybe it was the difference in quantity as I only eat when I’m hungry regularly, whereas there I was eating whenever I had an opportunity and wasn’t absolutely sick of food.

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I think a cycle is absolutely important, if for no other reason than to avoid unforeseen collision among the effects of the various supplements. Also maybe to prevent the body from getting habituated to any of them. This is a strong intuition of mine, informed mostly by Nassim Taleb’s work on how non normal but rather fat tailed distributions prevail in the world. He mentioned somewhere in Fooled by Randomness but didn’t provide a source (though maybe it was a footnote that I simply couldn’t access as it was an audiobook that I listened to), that there were studies showing how humans metabolized fat / protein better if it was administered only a couple of days a week. That thought stayed with me and got me thinking of intermittent fasting too.

When it comes to supplements I’m sure the body wants to return to homeostasis and eventually finds ways around what we’re doing to it so we need to keep it guessing.

Or maybe this is a rationalization of mine for why some days I remember to take my supplements and stuff dozens of pills down my throat, and other times I just shrug and go without.

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Cycling and timing are important issues. For some molecules it is hours, for some it is weeks. For things like GTN it is minutes. Hence experiments that don’t resolve timing issues are likely to be meaningless.

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Is this something that you do yourself, or a treatment done by a dermatologist?

Oh I do everything myself. Thought I’d covered it in another thread on skincare a while back.

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I could not find it @medaura. What is the RF microneedling device you are using?

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Whatever it was-I need some! You look fantastic!

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You’re too kind. My theory re: skin rejuvenation in particular is that it takes a controlled demolition of the status quo and good nutrition to rebuild it right. By the former I mean some sort of trauma, usually heat induced, or mechanical (RF and microneedling being great examples of each) and good nutrition / supplements to make sure it gets rebuilt right. I have historically put little stock in topicals as they don’t penetrate well and most cosmetic formulations are meant just to feel good, not as a transdermal drug delivery systems. I used to make my own cosmetics for private consumption which were based on patents and research papers on the latter. Think micro emulsions, nano emulsions, liposomes, but it was such a pain in the ass that I shifted focus on procedures instead. As @scta123 noted upthread, it takes time for this sort of thing to yield results. The first 3 times I did it there was zero difference after. The 4th time I could see something and the 5th I was really sure it was working.

I also use a Q Switched ND YAG laser for the lips as that’s an area not to be micro needled. It’s based on this study where the results look amazing:

https://www.tandfonline.com/doi/full/10.1080/14764172.2022.2120620

Scroll till you see the before and after photos. I’ve only done about 3 sessions so far and my results are modest but I’ll keep going and hope to see the same change as they do in the study after a few months. My results so far:

IMG_7630
IMG_9285

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Also the conditions under which I self administer the laser treatment are comical or borderline insane, as I have to literally blindfold myself with safety goggles and just use my sense of touch to feel where the laser is hitting my lips. In my old country we have an expression, the cognate of getting hoisted with one’s own petard, “don’t end up gouging your eyes out when you go plucking your eyebrows.” I need to take precautions to not LITERALLY end up doing that, burning my eyes while trying to improve my skin and soft tissues. After a while I got used to it though and now I can laser myself blindfolded like a pro :laughing:

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@medaura you mention your general list of equipment you’ve tried in this post: Biohacking Devotees Spending Hundreds of Thousands—Even Millions—to Enhance Their Homes (WSJ) - #13 by medaura

But not the specific brand/source of the RF microneedling device. Can you please share the name and cost?

It seems the professional ones are in the $30K to $70K price range used:

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Every single one of my devices is from AliExpress. The RF microneedling one costs $350-400 and the disposable treatment heads + tubes are around $5-7 per treatment. A single treatment at the dermatologist office costs almost the same as the machine around where I live. So the price is right for me. If you want me to find the actual product I can do that better in front of my computer tomorrow.

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Oh man, it makes me nearly physically sick to think people pay such prices. The market is really inefficient! It makes me want to start a business of curating great beauty equipment and selling it at a decent though not exorbitant markup + educational materials for the home use folks. But my heart is not into it.

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@medaura I would really appreciate if you could post the list of devices you use. I tried to search AliExpress, but there are so so many options and mostly prices are much higher than you mentioned. You seem to have done a lot of research on this.

Yes, I was doing the same. First stared buying branded topicals, but I thought it was just a rip off and started mixing my own preparations, but topicals get messy, when you put what in what order etc. I stopped all that and settled with tretinoin some 10+ years ago. It serves me very well. I would want to avoid typical starting procedures like fillers and botox, I have seen so many faces ruined. I really like your DYI approach to procedures and machines.

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In using the search string “mtor rebound”, I found the study below:

https://www.sciencedirect.com/science/article/abs/pii/S0006291X19306667

Rebound pathway overactivation by cancer cells following discontinuation of PI3K or mTOR inhibition promotes cancer cell growth

Using the search string “fasting, refeed, skin ncbi” yields the following study.

The skin results are remarkable. As earlier commented, you look exceptionally good. But we need to hunt down the causative mechanism, so we can replicate your success.

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One sort of prosaic explanation for your vacation-associated dewrinkling might just be the shift from catabolic to anabolic: you ate more, got a little juicer, a little fatter, maybe upped your collagen production.

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