Rapamycin Extends Life and Health in C57BL/6 Mice

Abstract

Target of rapamycin inhibition by rapamycin feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated rapamycin or a control diet to C57BL/6Nia mice of both sexes starting at 19 months of age. We performed a range of health assessments 6 and 12 months later. Rapamycin feeding significantly reduced mTOR activity in most but not all tissues. It also reduced total and resting metabolic rate during the light (inactive) phase of the light:dark cycle in females only but had no effect on spontaneous activity or metabolism during the dark (active) phase of either sex. Males only had less fragmented sleep when fed rapamycin, whereas stride length and rotarod performance were improved in both sexes. Survival was also improved by this late-life rapamycin feeding, and some pathological lesions were delayed. We found no adverse health consequences associated with rapamycin treatment.

Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune‐deficient mice

“…We interpret the eRapa‐mediated 3.3‐ to 12‐fold augmented lifespan extension of IFN‐γ −/− and RAG2 −/− mice versus modest lifespan extension in syngeneic BL6 mice (Zhang et al ., 2014) as consistent with cancer and infection prevention as lifespan extension mechanisms of eRapa, seen in exaggerated form in these mice that are highly susceptible to cancers and infections. Given the importance of cancer to mortality, and the considerable immune modulating effects of eRapa, much additional work is needed.…”

“…It also significantly increased lifespan in IFN‐γ −/− mice (Fig. 5), each exceeding the typical ~10% median lifespan extension of eRapa and other known pharmacologic lifespan‐extending agents in wild‐type mice (Zhang et al ., 2014) by more than 3.3‐ or 12‐fold for IFN‐γ −/− or RAG2 −/− mice, respectively.…”

Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production

“…[14][15][16][17] This compound has attracted a great deal of attention due to its proposed ability to mimic caloric restriction, resulting in decreased protein translation, increased autophagy and increased health and lifespan. [18][19][20][21][22] These benefits were observed in both mice fed high-fat diets 20 and older mice 23 when fed rapamycin. Rapamycin has been suggested to elicit its antiaging properties by preventing senescence under conditions that would normally cause cells to irreversibly exit the cell cycle.…”

Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice

“…Hindlimb muscle strength was determined by measuring peak force using the Digital Grip Strength meter equipped with a Hind Limb Pull Bar Assembly (Columbus Instruments, Columbus, OH, USA) essentially as described before (Zhang et al., 2014). The grip force was observed over 10 trials and the maximum force was recorded.…”