Dr. Joan Mannick joins Krister Kauppi on the Master One Thing Rapamycin Longevity Series to discuss her extensive background in the space, the science of mTOR and its effects on aging, her approach and outlook on the space, and more.
Dr. Mannick discusses how mTOR affects aging, cellular functions, and the immune system. Low-dose mTOR inhibitors may boost antiviral immunity and help create targeted vaccines for older adults. Research shows that mTOR inhibitors like rapamycin can promote longevity.
As Rapamycin, an FDA approved mTOR inhibitor has been proven to extend lifespan in numerous organisms, Tornado has been working to develop next generation rapamycin derivatives that aim to increase healthspan in humans.
Dr. Joan Mannick, CEO of Tornado Therapeutics, a Cambrian Bio PipeCo, says rapamycin is better validated than any other therapeutic for targeting aging and extending lifespan.
mTOR inhibitors prevent age-related physiologic decline and lengthen healthspan. Licensed compounds will be developed by new Cambrian subsidiary Tornado Therapeutics, led by Joan Mannick, M.D. as CEO.
mTOR coordinates cell growth/metabolism with nutrients/growth factors. It regulates protein synthesis/autophagy and affects cancer/diabetes/aging. Recent research advances its understanding and therapeutic targeting for human disease.
Inhibiting protein kinase mTOR with rapamycin promotes longevity in model organisms. Scientists aim to treat aging-related conditions by specifically inhibiting mTORC1. We review rapamycin's effects on mouse longevity and disease models, and explore clinical trials of mTOR inhibitors. New molecules may allow safer and more selective mTORC1 inhibition. We discuss the remaining work and questions to make mTOR inhibitors standard care for aging-related diseases.
The COVID-19 pandemic highlights the need for therapies that improve immune function in older adults, including IFN-induced antiviral immunity that decreases with age. RTB101, an oral mTOR inhibitor, increased IFN-induced antiviral gene expression and decreased respiratory tract infections in a previous trial. We investigated whether RTB101 upregulated IFN-induced antiviral responses and decreased viral RTI incidence when given once daily for 16 weeks during the winter cold and flu season.
mTOR inhibition extends lifespan and improves immune function in model organisms. This clinical trial aimed to determine if a low-dose mTOR inhibitor could decrease infection rates in elderly subjects. A combination of BEZ235 and RAD001 was safe and significantly reduced infection rates for a year after treatment initiation. Antiviral gene expression was also up-regulated and response to the flu vaccine improved. This suggests that selective TORC1 inhibition could benefit immune function and decrease infections in the elderly.
Inhibition of mTOR extends lifespan and delays age-related diseases in mice, but its effects on humans are unknown. To assess these effects, RAD001 was tested on elderly volunteers to see if it improved their response to the flu vaccine. RAD001 enhanced the response by 20% and reduced the expression of the PD-1 receptor, which inhibits T cell signaling and is more highly expressed with age. This suggests that mTOR inhibition may benefit immunosenescence in the elderly.
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