(not to mention increases in blood pressure AND insulin resistance)
All of this is compatible with slower cellular aging (b/c the nutrients are not IN the cells where they can promote growth/cause damage), but it does mean one needs better diagnostic tools (eg continuous measures of inflammation or 8-oxo-G or ROS)
The effect of rapamycin and rapalogs on the cardiovascular system initially was not clear, especially in humans. In clinical studies with transplant patients, rapalogs induced a negative plasma cardiovascular risk profile, e.g., an increase in LDL cholesterol and triglyceride concentrations in plasma [47]. Rapamycin also has been reported to have deleterious effects on endothelial function (ability of a blood vessel to constrict and dilate) in laboratory animals and in human coronary arteries from sirolimus-eluting stents [48, 49]. Rapamycin also has been reported to accelerate senescence of endothelial progenitor cells [50]; however, as described below, most of the recent studies indicate that rapamycin reduces cellular senescence. Overall, these early studies are in conflict with the large number of studies in mice listed in Table 4 that have studied the effect of rapamycin on atherosclerosis in mice.
Mueller et al. [54] reported that the blood levels of LDL and VLDL cholesterol were slightly higher in the everolimus-treated mice but observed no change in triglycerides. It is interesting to note that Ross et al. [55] observed no effect of rapamycin (1.0 mg/kg/day) treatment on blood triglyceride levels in the non-human primate, marmoset.
I mean, ex-Malaysian PM Mahathir Mohamad is enough proof that heart disease risk is not the same thing as aging rate.
Interesting info. But first, only rats involved. Second, only daily intake involved.
I am on rapa since june last year, first once weekly and now every two weeks with GFP (grafe fruit protocol) to increase bioavailability by 300%. The dosing is 6 mg. (real 18mg. by means of GFP) and my weight is 85kg. and 189 cms. height. This intermittent dosing is supposed to avoid chronic daily dosing unwanted side-effects, with rapa peaks favouring inhibition of mTOR Complex 1 (mTOR C1) while leaving mTOR C2 mostly unaltered, which is a positive factor for our health. From what I’ve learned mainly from Dr. Alan Green’s comments at Rapamycin Therapy this is the way to behave to increase bioavailability while simultaneously avoiding side effects.
What are your thoughts about this dosing regime in particular?. I’ll love to learn from your own experience on rapa dosage and timing.
Wow! What an excellent overview of rapamycin studies… and many benefits neurological… senescence, circulatory, cancers and cognitive.
And concludes… human trials are needed… particularly in Alzheimer’s. We see Dr. Ai Ling Lin has started research in Alzheimer’s with a small study. Let’s hope it expands.
example, a study conducted among healthy individuals taking rapamycin (1 mg/day orally, for 8 weeks) reported a within-group increase in serum triglyceride concentration of about 40% above baseline (p=0·05); however, this change was not statistically significant when compared with the placebo group (p=0·12).36 Additionally, a study on patients with multiple system atrophy reported a significantly higher number of adverse effects in the rapamycin group (2–6 mg/day orally, for 48 weeks) compared with the placebo group; the most prevalent adverse effects in this study were infections (urinary tract, upper respiratory, and skin infections and sinusitis) and oral and labial pathology (aphthae, gingivitis, and herpes-like vesicles).41 A study on patients with pulmonary hypertension reported a statistically significant increase in concentrations of total cholesterol and triglycerides in the group taking everolimus (0·75 mg orally, every 12 h for 2 days, followed by adjustments to maintain target serum concentrations at 5–8 ng/mL over 6 months), compared with baseline.43 In patients with rheumatoid arthritis, everolimus (6 mg/day orally, for 12 weeks) was associated with modest increases in the concentrations of total cholesterol, LDL cholesterol, and triglycerides, which returned to baseline after the 12-week treatment.44
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this can be useful to query with elicit or deep research