Discontinuation of rapamycin results in robust but selective senescent enhancer activation and exacerbation of the SASP

It’s not so much “reversal of benefits” as it is what John Hemming has mentioned - the return of the harmful SASP levels once you stop rapamycin, so the resumption of damaging processes. During the time you are on rapamycin you are effectively pausing a lot of the damage (at lease the subset of damage that is caused by SASP), is what this research is suggesting.

I think like most things; it’s a balance. If you take too much rapamycin for too long you risk blocking mTORC2, and getting negative side effects like blood lipid or glucose disregulation. But of course “what is too much, for too long” is going to vary by person and situation… so its all very difficult to parse out right now due to individual differences and lack of robust clinical trials.

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SASP has negative effects. I think it is through Il-10, but that is contrary to the conventional wisdom.

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I was starting to get side effects from 6mg per week (not sleeping well, not feeling good in the days after a dose, worsening of existing chronic pain). I’ve tried a few different dose regimens now, so I decided to try 1mg daily for 1 month following the recent small studies on APOE4/4 participants, as I have APOE4/4 and that’s my main reason for taking Rapa.

Anyway, I’ve nearly completed the month and have had no sides other than the occasional painless tiny lump somewhere in my mouth. I’ll go back to 6mg weekly after this to see if the side effects come back. I did have a medical checkup after 3 weeks of daily Rapa and my LDL-C was 46 (Brillo EZ, Ator 20mg) and my HbA1c was 5.1% (Acarbose & Dapa), so I was happy about that. Unfortunately, routine NHS checkups in the UK are not very extensive and that’s all they tested for, which is a bit of a waste but better than nothing.

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I’m doing well on 3 ng per week. Higher dose makes me sick. I think it’s weight dependent. I’m only 110 lbs.

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Randox and medicheck both do reasonable broad blood panels. Randox has a lot of tests.

Yes. Dosing is definitely weight dependent. A lot of lighter folks here cannot handle normal weekly doses without severe side effects. The dosing amount is different from.person to person. You also need the goldilocks dose. Too little does nothing and too much is annoying due to side effects.

Rapamycin blood tests should help you find your sweet spot.

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I’m 120lbs and had no problem taking 10mg/week for months. I backed off to 7mg to ensure clearance by the next dose.

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Yes, probably backing down was a good choice… too high and MTOR2 is affected… and you age faster. I did much higher for 7 months and did not feel a problem (silent pathology)… but inflammation and methylation test said otherwise. Lost some of the rejuvenation I had gained.

For me 6 - 8 mg is my sweet spot for catabolic and anabolic balance. Now my biological tests show I regained those years back.

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I forgot you had spoken about that here a while back. To be clear, your current dose is 6-8mg once every 7 days?

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Exactly… pure pharmaceutical grade zydus.
2 mg pills… I take 3 pills … so 6 mg once a week. Mostly 6 mg past 7 months.

I will do a blood test in 2 weeks and test my blood absorption at 3 hours… C-max.

Average person get 3 ng/mL per 1 mg. So should be at 18 ng/mL at 6 mg dose.

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I think the dosage is not only related to body weight, but also to gender.

Generally, the dosage for women is less than that for men. Perhaps because men have a higher tolerance level than women.

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Yes! Most research says women get same bang at a lower dose than men at a higher dose.

Men processing… faster… metabolism… more cells than women…might require men to have a higher dose than women.

More for women does not show increased benefits in longevity.

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Blueberries and fruit in general don’t grow year round - that’s an artifact of modern supply chains. Fruit, and all food are incredibly complex chemically. They have some defensive chemicals, which in small amounts are beneficial through hormesis, but what if you eat them “unnaturally” long? Toxins might accumulate and be a net negative. Especially with modern growing methods

I’m with you on pesticides, but I think it’s important to point out that modern growing techniques have led to a reduction in the levels of nutrients in our foods (see, for example, this news report Why modern food lost its nutrients).

I’m not at all concerned about consuming too many naturally occuring defensive chemicals year-round when modern farming practices have made our food less nutricious and full of chemicals whose effects we still don’t fully understand.

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I think that was the core message of the PEARL study. Women saw benefits at the low dose while men did not.

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Dr. Blagosklonny wrote in his later years that he use to cycle on and off rapa, but later became convienced that his cancer got a hold in his body when he was not on drug during on of these cycles. I started rapa at 71 and I am 79 now never stopped. Also, just started low dose Retatrutide to lose a few pounds, but to mainly reset my mitocondria balance. Unlocking longevity with GLP-1: A key to turn back the clock? Unlocking longevity with GLP-1: A key to turn back the clock? - PubMed

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I am turning 23 next month and my weight is around 70 kg, which has been constant for 2-3 years. I have been taking 12 mg of rapamycin weekly for around 2 years of now, and the only side effect I felt was fatigue on the day of taking rapamycin & very rare mouth sore. so I’ve been dosing it just after lunch at around 2 o’clock in the afternoon and not eat after. Recently, my lipids were also fine: the LDL was around 55, and everything related to glucose metabolism was also fine. NEVER TOOK A BREAK in last 2 years , only one time got ldl high as 115 in test, I have also been dosing empagliflozin (6.25mg) in the morning just after breakfast to control my glucose metabolism and also using Metformin (500mg of sustained release) in the afternoon just before lunch.

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Great to see your post Jack

Appears all is going excellent.

You will beat the old age record for men yet. And, have amazing health to boot :boot:.

Jealous that rapamycin is available for you to purchase easily in India.

TBH - your dose seems high to me for your young age… watch that MTOR2… we need anabolic too! It can be silent pathology… a good inflammation test like GlycanAge or methylation test like TruMe Labs can help monitor the MTOR2.

But youth is on your side. :stuck_out_tongue::wink:

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Nobody knows if what you are doing is right or wrong. Only time will show.

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I’ve settled on 5mg once every 3 months. Treating more like a fast. No idea whether this is the best approach though

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well I may be dosing higher than usual considering my age, but I tried taking a break for 15 days & I got sick twice in that period, other than that I never caught a cold or any sickness in last 2 years considering bad air quality & hygeine standards in india, in another instance got shin splints due to continuous running & my physio told it will take at least 3 to 5 months to recover, kept the rapamycin doses at 12 mg & recovered in about 14 days max. I m never leaving this drug again, maybe once i think of becoming a father, but in my case high & continuous doses work like charm

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