A new review paper coming out…
Rapamycin, an antibiotic discovered in the 1970s from Streptomyces hygroscopicus on Easter Island (Rapanui), has become a critical tool in biomedical research. Initially recognized for its potent antifungal and immunosuppressive properties, rapamycin has recently gained significant attention for anti-aging therapy and seizure treatment via mTOR pathway inhibition. The mechanistic target of the rapamycin (mTOR) pathway is an evolutionarily conserved metabolic signaling cascade that regulates cell division, growth, and survival. There is growing evidence that mTOR pathway activity accelerates aging and the development of age-related diseases including cancer, atherosclerosis, diabetes, and declining immune function. Therefore physicians and ‘biohackers’ are using mTOR inhibition via rapamycin (and rapamycin analogs) off-label for prevention of age-related conditions despite not being widely recognized as a treatment by the broader clinical community. Currently, rapamycin (i.e., sirolimus and everolimus) is FDA approved for the prevention of transplant organ rejection and for anti-seizure therapy in Tuberous Sclerosis Complex (TSC; caused by variants in TSC1 or 2),we aim to summarize the mTOR pathway, the impact rapamycin has on the mTOR pathway, and the state of rapamycin use in the field of aging and longevity. Importantly, we will discuss the gaps in knowledge, pitfalls, and potential for the use of rapamycin to prevent aging/age-related disease and discuss the lessons learned from achieving FDA approval of evirolimus for TSC-related seizures after many years of off-label use.
.Frontiers | Rapamycin for longevity: the pros, the cons, and future perspectives
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Hit that “notify”, who knows how long it’ll take😳.
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Published and open access.
I find it disappointing that they only quote the older, lower life extension studies rather the newer and greater results from the more recent ITP studies.
Yeah, I got the email alert for the publication. It’s a rather odd paper, I think. A review that’s not very comprehensive, with notable omissions, like a mention of a review:
“ A systematic review evaluated the effects of rapamycin and its derivatives on aging-related physiological changes and diseases and found improvements in the immune, cardiovascular, and integumentary systems but not in the endocrine, muscular, or neurological systems (Lee et al., 2024). Interestingly, this contrasts with robust neurological effects observed in preclinical models of epilepsy associated with mTOR pathway hyperactivating variants (“mTORopathies”) where rapamycin prevented seizures and corrected structural abnormalities (Zeng et al., 2008; Iffland et al., 2022).”
that mentioned a lack of effectiveness of rapamycin in endocrine, muscular and neurological systems. The authors did some pushback on neurological systems effectiveness, but ignored evidence on impact on muscular and musculoskeletal system which has been widely reported on among others in the PEARL trial which they referenced - btw. I just posted a yt video presentation by Mannick discussing the highly beneficial impact of rapamycin on muscle neurological connections. All completely ignored, despite wide reports by the very “biohackers” whom they credit as inspiration in this bizarre acknowledgment:
“Acknowledgments
We would like to thank the reckless biohackers and wellness influencers around the world who inspired this work.”
Wha?? Come again?
Meanwhile they spend paragraphs on worried speculation about the theoretical dangers of rapamycin shortages should rapamycin become popular and the inequities of unaffordability of rapamycin to the poor. Just weird, given how misplaced such fears are - rapamycin being a dirt cheap generic. Odd.
Makes one wonder what’s behind the creation of such odd papers.
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I am working on a Poster for the British Society for Research on Aging conference 2025, part of this poster will look at Rapamycin dosage and the interplay between the PINK1/Parkin style of mitophagy which is selective as to Mitochondrial Membrane Potential and other systems of mitophagy.
There is also an interesting question as to what can be done with dormant cells (stem and oocyte)
That I think is what we need to be looking at. The work I need to do behind this is mainly reading, but I am quite busy at the moment so I expect to do this in August.
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