Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to.
Calorie restriction (CR), which deactivates the nutrient-sensing mTOR pathway, slows down aging and prevents age-related diseases such as type II diabetes. Compared with CR, rapamycin more efficiently inhibits mTOR. Noteworthy, severe CR and starvation cause a reversible condition known as "starvation diabetes." As was already discussed, chronic administration of rapamycin can cause a similar condition in some animal models. A recent paper published in Science reported that chronic treatment with rapamycin causes a diabetes-like condition in mice by indirectly inhibiting mTOR complex 2. Here I introduce the notion of benevolent diabetes and discuss whether starvation-like effects of chronic high dose treatment with rapamycin are an obstacle for its use as an anti-aging drug.
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA. blagosklonny@oncotarget.com
Mikhail V
MV
Blagosklonny
D000375:Aging / Q000187:drug effects*; D000818:Animals; D031204:Caloric Restriction; D003920:Diabetes Mellitus / Q000139:chemically induced*; D006801:Humans; D007333:Insulin Resistance; D020123:Sirolimus / Q000494:pharmacology*; D013217:Starvation / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus