New Rapamycin Research Papers - Aug, 2022

A few new papers came out recently on or related to rapamycin and mTOR. I’ve contacted the authors on the first paper to try to get a copy, and the second paper is open access.

Contemporary mTOR inhibitor scaffolds to diseases breakdown: A patent review (2015–2021)

Highlights

• Structures and activities of novel mTOR inhibitors patented between 2015 and 2021.

• A current overview of PI3K/AKT/mTOR signaling pathway.

• Targeting on cancer, neurodegenerative diseases, diabetes, obesity and aging.

• mTOR inhibitors biological data.

mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.

Special Issue “Frontiers in mTOR Signaling”

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“Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signaling and feasible for application in the human population.”

Maybe rapamycin doesn’t do that much in life extension if you are doing everything else right.

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Ha - the definition of “doing everything else right” in caloric restriction terms is reducing your diet by about 40%, which is really hard, painful, and cold…(I know, I’ve tried it for a year). I suspect the percent of the population that can pull this off and enjoy life at the same time is a pretty tiny fraction. But sure, for that tiny fraction of the populace, perhaps there is minimal benefit from rapamycin :slight_smile:

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If someone already posted this I missed it.
A little bit of negative press for rapamycin.
Not sure what to make of it.
“A Popular Drug Increases Alzheimer’s-Associated Plaques”

Yes - a long discussion on this study here: Rapamycin increases Alzheimer's-associated plaques in mice, study finds

That first article isn’t good news either, thymus involution is no good. I hope these mice are more on a immunosuppressive schedule than what they were getting in the ITP trials …

Another new paper:

rapamycin may be effective as a chemopreventive agent, suspending progression of low-grade cancers, preventing invasive conversion of in situ malignancy, or delaying malignant transformation of established pre-malignant conditions.

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