-
Take a look on Research Tab & see printable PDF
-
Here it is Dan: https://www.societyforagereversal.org/ageupdate
-
Thanks Seaside & Maximus.
OK great. Taking the procedure in order
- Inhibit mTOR (rapamycin). I'll suggest again for people to look into water only fasting (> 3-4 day) as a simpler, and I believe better way to cycle your mTOR. One thing is that mTOR isn't bad, but that we want it to cycle, and the way it evolved into our physiology is by periodic fasting. See the research (and book) by Dr Valter Longo on this, or a web search will bring up lots of materials. One reason I think this is preferred is because a fast, where you switch to ketone bodies, affects every cell in your body, whereas pharmaceuticals typically only affect some parts of your body and don't propagate throughout. Another reason is that fasting has many longevity benefits beyond just mTOR (it also goes after senescent cells, see below). The downside is fasting isn't a easy or pleasant experience.
- NAD+ restoration - easy enough
- Eliminate senescent cells. Again fasting, when you go into a prolonged fast your body goes into the anabolic state where it starts getting calories from wherever it can find them, since it's not getting them from your food (catabolic). So it goes after your fat stores, and it goes after all the junk like senescent cells. Your body sees useless junk like fat, senescent cells, crud in your blood vessels as dinner and recycles them for energy! When you're in the catabolic state your body is too busy doing that to clean up the house.
- Stem cells. Pretty hard for most of us to get this treatment. But at the risk of sounding like a broken record, going on a fast also has the effect of your body killing off half of your T-cells, for example (dinner!). You have old T-cells that aren't doing much, leftover from a previous illness. In the re-feeding period those are regenerated from fresh stem cells, just like a baby.
Anyhow, just a plug for water only fasting which for reasons I don't understand doesn't seem to be generally known of followed by the longevity crowd.
-
Reading further
AMPK is a master energy sensor in cells. When AMPK is activated by exogenous compounds (like metformin), cells think they are energy deprived. This prompts cells to turn down mTOR and utilize their fat stores for energy production.
This is precisely the process that happens during fasting. After the glucose stores are depleted (about a 24-32 hours) the cells actually are being energy deprived, so they turn down mTOR and the body turns on ketosis, which is turning fat into ketones for your body to use for energy. And as I say, every single cell in your body is forced to do this because there's no glucose to burn anymore. So, for a time, your cycling mTOR very strongly via the catabolic/anabolic processes. I suspect this is the best way to approach this, not through a steady state suppression, but via a cycling approach. I wrote a post about this cycling concept in the General forum.
-
Dan Mc It sounds like you're pretty well-read, Dan.
Just one correction: fasting causes a "catabolic" state, and food is "anabolic" (you have them switched in your previous post).
-
-
Maximus Thanks - I tend to get those backwards randomly
FYI Bill gave his RAADfest presentation at the last Church of Perpetual Life get together
https://www.youtube.com/watch?v=p0JlJpH0UMs
-
There is an amendment (notified by email today) in the order of intervention with more focus on metformin as botn AMPK activator and mTOR inhibitor (vs rapamycin).
I report the note from Faloon:
"...Our investigations and partial validations resulted in the dissemination of the following multi-step approach to biological age reversal at RAADfest:
Step 1: Inhibit mTOR and induce autophagy with rapamycin (or AMPK nutrients
and/or intermittent fasting and/or calorie restriction)
Step 2: Repair cellular DNA by boosting NAD+
Step 3: Purge senescent cells using two doses of dasatinib + quercetin
Step 4: Systemic rejuvenation with young plasma and/or stem cells
We are amending this sequential order in this email.
Based on ongoing clinical research, we believe most of you are already sufficiently inhibiting mTOR with metformin and/or nutrients like gynostemia leaf extract and hesperidin (found in the AMPK Activator nutrient formula).
Low-calorie diets and exercise also indirectly suppress mTOR (via activation of cellular AMPK).
So as of this date, we are revising the age-reversal protocol as follows:
Step 1: Inhibit mTOR/induce autophagy with metformin
(or AMPK nutrients)
Step 2: Repair cellular DNA by boosting NAD+
Step 3: Purge senescent cells using two doses of dasatinib + quercetin
Step 4: Systemic rejuvenation with young plasma and/or stem cells..."Beneficial effects on humans and differentiating between metformin and rapamycin need to be assessed, but it seems established the mechanisms are different. I understand rapamycin is directly inhibiting mTORC1 (chronic use might also result in inhibiting mTORC2 though which might not be good). Other molecules such as aspirin and metformin feature an indirect inhibition of mTORC1. Metformin seems to regulate REDD1 which promotes TSC2 which leads to inhibit mTORC1 and this independently from the metformin AMPK activation path (e.g. see Kalender et al 2010).
Any comment from the community of the amendment and direct/indirect mechanisms of actions?
-
albedo What mail list is this? I'm considering/about to join the self testing program, would be nice to make sure I'm kept up to day.
-
Dan Mc
Hi Dan. The email came from Society for Age Reversal <info@rescueelders.org> on Oct. 18th and had as subject: "Follow-Up Summary for RAADFest 2018". I guess you should receive it too when registering to the site, I only did that.
-
albedo Hunh? I was subscribed, maybe with the changeover to the new site it got lost. <gripe> Grrr ... OK done but I won't get previous emails, and that had to be the most annoying reCAPTCHA I've ever done. reCAPTHCA should be banned from the internet, it's the most annoying and fragile system ever </gripe>
-
