I wonder if the key mechanism that Rapamycin works on for reduction of muscle aging is via the reductions in inflammation.
See new study below, and the well known anti-inflammatory impact of rapamycin in studies at the bottom:
Purpose: Chronic low-grade systemic inflammation affects muscle protein metabolism. The dietary inflammatory index (DII®) is a tool designed to assess the inflammatory potential of the diet.
Conclusion: Higher E-DII score is associated with lower muscle mass and muscle strength, and increased likelihood for the combination of low muscle mass and low muscle strength in older adults. This has important implications for healthy aging.
New Source Research Paper:
Association between dietary inflammatory index score and muscle mass and strength in older adults: a study from National Health and Nutrition Examination Survey (NHANES) 1999-2002
Rapamycin and Inflammation:
Results: We found that rapamycin reduced NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-κB activation. Moreover, mTOR siRNA inhibited NF-κB activation, leading to the suppression of NLRP3 inflammasome activation.
other studies on rapamycin and inflammation reduction:
Nice studies. There’s really no debating any longer the role of chronic inflammation in all things aging. I’m sure that the anti inflammatory component of rapamycin is yet another attribute.
Lycopene also has significant anti inflammatory activity and apparently
will lower LDL by about 10% with doses over 25 mg.
I Will start with two, one I really like and one I personally detest in spite of the evidence.
Boswellia serrata, Indian frankincense, is one amazing supplement for some people. Strangely it is most effective for knee pain.
Curcumin: I really don’t like it because it doesn’t like me. I have given it a try many times over the years with different brands, doses, and regimens because it is so highly touted. It only ever gave me heartburn, etc. regardless of taking it on a full stomach or empty stomach. It never produced any discernible results for me. And in addition, I don’t like curried foods.
A fairly recent meta-analysis of Boswellia serrata:
Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks.
and
Boswellia is used to:
Treat arthritis
Help with asthma
Treat colitis (inflammation of your colon)
Help with inflammation (swelling and redness)
Help reduce fluid cerebral edema (brain swelling) after radiotherapy, in patients with brain tumors
Help reduce skin damage due to radiotherapy, in breast cancer patients.
I do believe inflammation is the key to biological aging. I took an epigenetic spit test in January two weeks after I got my 3rd COVID booster and the result was that I was 19 years older than my chronological age (66 vs 47). I called up the lab to protest and they told me the vaccine was the reason as I had a lot of inflammation (2 weeks is supposedly the high point for vaccine inflammation and antibodies). They offered me a free test to make up for the one that gave me such a wrong answer. I’m curious what the new results will be.
As an aside, I plugged my blood test results from February into Aging.ai and my blood is only 26 years old. So if you average my blood age and spit age together, you get my chronological age. The truth is probably somewhere in between the extremes…
That’s probably just a correlation: to gain or even maintain muscle mass you need a high quality protein rich diet and exercise. Muscle and exercise also make you more insulin sensitive which reduces inflammation
Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation
Results
ACA, Rapa, and 17aE2 (in males, but not in females) oppose age-related increases in the MEK1- ERK1/2-MNK1/2 cascade, and thus reduce phosphorylation of eIF4E, a key component of cap-dependent translation. In parallel, these treatments (in both sexes) reduce age-related increases in the MEK3-p38MAPK-MK2 pathway, to decrease levels of the acute phase response proteins involved in inflammation.
Conclusion
Each of three drugs converges on the regulation of both the ERK1/2 signaling pathway and the p38-MAPK pathway. The changes induced by treatments in ERK1/2 signaling are seen in both sexes, but the 17aE2 effects are male-specific, consistent with the effects on lifespan. However, the inhibition of age-dependent p38MAPK pathways and acute phase responses is triggered in both sexes by all three drugs, suggesting new approaches to prevention or reversal of age-related inflammatory changes in a clinical setting independent of lifespan effects.
This is good, more fundamental understanding of intracellular pathways and immune response activated to deliver longevity enhancements. Although rapamycin might deliver the highest longevity benefit in mouse models, applying it to humans is fraught with dosing/side effects issues, potentially severely limiting translation. Perhaps one of these other molecules (and new ones discovered that target these pathways) will deliver BOTH significantly improved lifespan and far lesser side effects…in human translation.
Furthermore, once again, liver and kidney were tissue signalling hubs: “To evaluate effects of age and anti-aging drugs on the MEK1 kinase cascade, we collected lysates from livers and kidneys”
Indeed, this is the magic phenol molecule in EVOO. When I look for EVOO, I look for highest oleocanthal, normally only buy from vendors who can produce 3rd party lab analysis. You can tell a high oleocanthal EVOO by tasting it…if it dosen’t burn your throat, it’s not high level. I really go out of my way to procure high oleocanthal grades, typically come from Greece/Cyprus/Italy.
There are have been many intervention studies using EVOO.
A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study
Critical Review on the Significance of Olive Phytochemicals in Plant Physiology and Human Health
You absolutely do NOT need a high protein diet to maintain muscle mass. In fact, Dr B says “amino acids don’t build muscles, resistance exercise does”, and the science backs this. I eat approx 50g/day (a far lower intake compared to historical in the switch to a ketogenic diet) but do daily 45 minutes of resistance exercise. Massive growth in my musculature…they didn’t come from eating extra protein (in fact, eating LESS), 100% from resistance exercise.
Identifying the Structural Adaptations that Drive the Mechanical Load-Induced Growth of Skeletal Muscle: A Scoping Review
Mechanical load can build muscle several ways.
A. myofiber hypertrophy, (B) myofiber splitting or hyperplasia, or (C) longitudinal growth of myofibers that exhibit intrafascicular terminations
I think of EVOO as compared to wine; with much better value and health benefits than a bottle of good wine. A bottle of good wine is expensive and FLEETING, with almost no health effects (arguably, negative health effects). Yet this bottle of EVOO, cheaper by the mL than a good bottle of wine lasts me a LONG time and is infinitely higher in health benefits.
